Meningococcal Infections
Conditions
Keywords
Meningococcal disease,, Neisseria meningitidis serogroup B,, Prevention,, Vaccination,, Infants
Brief summary
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.
Interventions
BIOLOGICALrMenB+OMV NZ
BIOLOGICALcombined diphtheria,tetanus,pertussis+polio+Hepatitis B+Haemophilus influenzae B vaccine
BIOLOGICALPneumococcal vaccine
Sponsors
Novartis Vaccines
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Days to 89 Days
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | One month after third Men B vaccination | 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. |
| 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 | 10 months (groups 1 and 2); 8 months (groups 3 and 4) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Non-inferiority of Immune Response to rMenB+OMV NZ Vaccination When Administered Concomitantly With Routine Infant Vaccines at 2,4,6 Months of Age | One month after 3rd Men B vaccination | 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. |
| Non-inferiority of Immune Response to Diphtheria and Tetanus Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine | One month after 3rd vaccination | 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 with antibody concentrations ≥0.1 IU/mL against Diphtheria and Tetanus antigens as measured by enzyme-linked immunosorbent assay. |
| Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | One month after third Men B vaccination | 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. |
| Geometric Mean Ratio of hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | one month after third Men B vaccination | 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. |
| Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | One month after third Men B vaccination | 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. |
| Percentage of Subjects With 4-fold Rise in hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | One month after third Men B vaccination | 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. |
| Non-inferiority of Immune Response to Acellular Pertussis Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine. | 1 month after 3rd vaccination | 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. |
Countries
Belgium, Czechia, Germany, Italy, Spain, United Kingdom
Participant flow
Recruitment details
Subjects were recruited from 4 centers in UK, 5 centers in Italy, 16 centers in Spain, 6 centers in Belgium, 25 centers in Germany and 4 centers in Czech Republic
Pre-assignment details
All subjects enrolled were included in the trial.
Participants by arm
| Arm | Count |
|---|---|
| B+R246 Subjects in this group received rMenB+OMV NZ vaccine at 2, 4, and 6 months of age, administered concomitantly with routine infant vaccinations | 627 |
| B246_R357 Subjects in this group received rMenB+OMV NZ vaccine at at 2, 4, and 6 months of age; routine infant vaccinations were administered at 3, 5 and 7 months of age | 628 |
| B+R234 Subjects in this group received rMenB+OMV NZ vaccine at 2, 3, 4 months of age, administered concomitantly with routine infant vaccinations | 318 |
| R234 Subjects in this group received routine infant vaccines administered at 2, 3 and 4 months of age. | 312 |
| Total | 1,885 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Administrative reason | 3 | 0 | 1 | 0 |
| Overall Study | Adverse Event | 4 | 7 | 2 | 0 |
| Overall Study | Inappropriate enrollment | 0 | 2 | 0 | 0 |
| Overall Study | Lost to Follow-up | 7 | 9 | 3 | 3 |
| Overall Study | Protocol Violation | 4 | 3 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 12 | 15 | 3 | 7 |
Baseline characteristics
| Characteristic | B+R246 | B246_R357 | B+R234 | R234 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 68.7 days STANDARD_DEVIATION 8.9 | 68.8 days STANDARD_DEVIATION 9.4 | 68.8 days STANDARD_DEVIATION 9.1 | 68.1 days STANDARD_DEVIATION 9 | 68.7 days STANDARD_DEVIATION 9.1 |
| Sex: Female, Male Female | 292 Participants | 312 Participants | 164 Participants | 159 Participants | 927 Participants |
| Sex: Female, Male Male | 335 Participants | 316 Participants | 154 Participants | 153 Participants | 958 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 620 / 625 | 623 / 627 | 316 / 318 | 305 / 312 |
| serious Total, serious adverse events | 63 / 625 | 57 / 627 | 19 / 318 | 19 / 312 |
Outcome results
Primary
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
Population: The analysis was done on the Modified Intention to Treat (MIIT) population, ie, enrolled subjects who actually received a study vaccination and provided at least one evaluable serum sample after baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| B+R246 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Post vaccination(NZ98/254 strain)N=555,559,284,269 | 79 Percentages of subjects |
| B+R246 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Post vaccination (44/76-SL)N=550,561,283,265 | 99 Percentages of subjects |
| B+R246 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Baseline (5/99 strain)N=580,577,294,289 | 5 Percentages of subjects |
| B+R246 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Post vaccination (5/99 strain)N=551,554,285,245 | 99 Percentages of subjects |
| B+R246 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Baseline (44/76-SL strain)N=587,589,300,291 | 9 Percentages of subjects |
| B+R246 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Baseline(NZ98/254 strain)N=582,583,298,292 | 3 Percentages of subjects |
| B246_R357 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Post vaccination(NZ98/254 strain)N=555,559,284,269 | 87 Percentages of subjects |
| B246_R357 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Baseline (5/99 strain)N=580,577,294,289 | 7 Percentages of subjects |
| B246_R357 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Post vaccination (5/99 strain)N=551,554,285,245 | 99 Percentages of subjects |
| B246_R357 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Post vaccination (44/76-SL)N=550,561,283,265 | 99 Percentages of subjects |
| B246_R357 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Baseline (44/76-SL strain)N=587,589,300,291 | 7 Percentages of subjects |
| B246_R357 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Baseline(NZ98/254 strain)N=582,583,298,292 | 1 Percentages of subjects |
| B+R234 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Baseline (44/76-SL strain)N=587,589,300,291 | 6 Percentages of subjects |
| B+R234 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Post vaccination (44/76-SL)N=550,561,283,265 | 99 Percentages of subjects |
| B+R234 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Baseline (5/99 strain)N=580,577,294,289 | 5 Percentages of subjects |
| B+R234 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Post vaccination (5/99 strain)N=551,554,285,245 | 100 Percentages of subjects |
| B+R234 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Baseline(NZ98/254 strain)N=582,583,298,292 | 2 Percentages of subjects |
| B+R234 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Post vaccination(NZ98/254 strain)N=555,559,284,269 | 81 Percentages of subjects |
| R234 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Post vaccination(NZ98/254 strain)N=555,559,284,269 | 4 Percentages of subjects |
| R234 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Baseline(NZ98/254 strain)N=582,583,298,292 | 1 Percentages of subjects |
| R234 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Post vaccination (5/99 strain)N=551,554,285,245 | 5 Percentages of subjects |
| R234 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Post vaccination (44/76-SL)N=550,561,283,265 | 4 Percentages of subjects |
| R234 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Baseline (5/99 strain)N=580,577,294,289 | 6 Percentages of subjects |
| R234 | Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | Baseline (44/76-SL strain)N=587,589,300,291 | 6 Percentages of subjects |
Primary
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)
Population: All subjects receiving at least one injection and providing post-baseline safety data (Safety Set).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| B+R246 | 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 | Vomiting (N=624,626,318,311) | 193 Number of subjects |
| B+R246 | 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 | Diarrhea (N=624,626,318,311) | 284 Number of subjects |
| B+R246 | 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 | Irritability (N=624,626,318,311) | 543 Number of subjects |
| B+R246 | 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 | Fever (≥38.0 C° %) ((N=624,627,318,311) | 501 Number of subjects |
| B+R246 | 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 | Unusual Crying (N=624,626,318,311) | 526 Number of subjects |
| B+R246 | 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 | Rash (N=624,626,318,311) | 84 Number of subjects |
| B+R246 | 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 | Erythema (N=624,626,318,311) | 506 Number of subjects |
| B+R246 | 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 | Tenderness (N=624,626,318,311) | 529 Number of subjects |
| B+R246 | 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 | Induration (N=624,626,318,311) | 447 Number of subjects |
| B+R246 | 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 | Swelling (N=624,626,318,311) | 290 Number of subjects |
| B+R246 | 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 | Sleepiness (N=624,626,318,311) | 523 Number of subjects |
| B+R246 | 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 | Change in Eating Habits (N=624,626,318,311) | 470 Number of subjects |
| B246_R357 | 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 | Induration (N=624,626,318,311) | 465 Number of subjects |
| B246_R357 | 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 | Vomiting (N=624,626,318,311) | 234 Number of subjects |
| B246_R357 | 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 | Erythema (N=624,626,318,311) | 516 Number of subjects |
| B246_R357 | 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 | Diarrhea (N=624,626,318,311) | 327 Number of subjects |
| B246_R357 | 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 | Swelling (N=624,626,318,311) | 324 Number of subjects |
| B246_R357 | 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 | Unusual Crying (N=624,626,318,311) | 515 Number of subjects |
| B246_R357 | 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 | Change in Eating Habits (N=624,626,318,311) | 473 Number of subjects |
| B246_R357 | 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 | Irritability (N=624,626,318,311) | 527 Number of subjects |
| B246_R357 | 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 | Sleepiness (N=624,626,318,311) | 525 Number of subjects |
| B246_R357 | 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 | Fever (≥38.0 C° %) ((N=624,627,318,311) | 447 Number of subjects |
| B246_R357 | 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 | Rash (N=624,626,318,311) | 130 Number of subjects |
| B246_R357 | 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 | Tenderness (N=624,626,318,311) | 491 Number of subjects |
| B+R234 | 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 | Change in Eating Habits (N=624,626,318,311) | 249 Number of subjects |
| B+R234 | 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 | Unusual Crying (N=624,626,318,311) | 268 Number of subjects |
| B+R234 | 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 | Induration (N=624,626,318,311) | 230 Number of subjects |
| B+R234 | 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 | Swelling (N=624,626,318,311) | 149 Number of subjects |
| B+R234 | 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 | Rash (N=624,626,318,311) | 42 Number of subjects |
| B+R234 | 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 | Sleepiness (N=624,626,318,311) | 282 Number of subjects |
| B+R234 | 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 | Vomiting (N=624,626,318,311) | 97 Number of subjects |
| B+R234 | 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 | Tenderness (N=624,626,318,311) | 265 Number of subjects |
| B+R234 | 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 | Irritability (N=624,626,318,311) | 289 Number of subjects |
| B+R234 | 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 | Diarrhea (N=624,626,318,311) | 138 Number of subjects |
| B+R234 | 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 | Erythema (N=624,626,318,311) | 257 Number of subjects |
| B+R234 | 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 | Fever (≥38.0 C° %) ((N=624,627,318,311) | 243 Number of subjects |
| R234 | 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 | Fever (≥38.0 C° %) ((N=624,627,318,311) | 160 Number of subjects |
| R234 | 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 | Induration (N=624,626,318,311) | 0 Number of subjects |
| R234 | 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 | Change in Eating Habits (N=624,626,318,311) | 159 Number of subjects |
| R234 | 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 | Vomiting (N=624,626,318,311) | 83 Number of subjects |
| R234 | 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 | Irritability (N=624,626,318,311) | 220 Number of subjects |
| R234 | 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 | Unusual Crying (N=624,626,318,311) | 186 Number of subjects |
| R234 | 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 | Rash (N=624,626,318,311) | 39 Number of subjects |
| R234 | 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 | Tenderness (N=624,626,318,311) | 0 Number of subjects |
| R234 | 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 | Erythema (N=624,626,318,311) | 0 Number of subjects |
| R234 | 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 | Swelling (N=624,626,318,311) | 0 Number of subjects |
| R234 | 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 | Sleepiness (N=624,626,318,311) | 224 Number of subjects |
| R234 | 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 | Diarrhea (N=624,626,318,311) | 113 Number of subjects |
Secondary
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
Population: PP Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| B+R246 | Geometric Mean Ratio of hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | 44/76-SL strain (N=501,507,262,236) | 58 Ratio |
| B+R246 | Geometric Mean Ratio of hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | NZ98/254 strain (N=504,503,258,238) | 11 Ratio |
| B+R246 | Geometric Mean Ratio of hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | 5/99 strain (N=497,494,257,217) | 430 Ratio |
| B246_R357 | Geometric Mean Ratio of hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | NZ98/254 strain (N=504,503,258,238) | 16 Ratio |
| B246_R357 | Geometric Mean Ratio of hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | 5/99 strain (N=497,494,257,217) | 553 Ratio |
| B246_R357 | Geometric Mean Ratio of hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | 44/76-SL strain (N=501,507,262,236) | 83 Ratio |
| B+R234 | Geometric Mean Ratio of hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | NZ98/254 strain (N=504,503,258,238) | 10 Ratio |
| B+R234 | Geometric Mean Ratio of hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | 5/99 strain (N=497,494,257,217) | 271 Ratio |
| B+R234 | Geometric Mean Ratio of hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | 44/76-SL strain (N=501,507,262,236) | 61 Ratio |
| R234 | Geometric Mean Ratio of hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | 5/99 strain (N=497,494,257,217) | 1.03 Ratio |
| R234 | Geometric Mean Ratio of hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | NZ98/254 strain (N=504,503,258,238) | 1.05 Ratio |
| R234 | Geometric Mean Ratio of hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | 44/76-SL strain (N=501,507,262,236) | 0.91 Ratio |
Secondary
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
Population: PP Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| B+R246 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | Baseline (NZ98/254 strain)N=554,543,283,278 | 1.13 Titers |
| B+R246 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | Baseline (44/76-SL strain) N=556,548,285,277 | 1.49 Titers |
| B+R246 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | post vaccination (5/99 strain)N=527,529,275,236 | 537 Titers |
| B+R246 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | post vaccination (44/76-SL) N=525,534,273,253 | 86 Titers |
| B+R246 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | post vaccination (NZ98/254 strain)N=30,534,274,257 | 12 Titers |
| B+R246 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | Baseline (5/99 strain) N=551,537,280,275 | 1.3 Titers |
| B246_R357 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | post vaccination (NZ98/254 strain)N=30,534,274,257 | 18 Titers |
| B246_R357 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | post vaccination (5/99 strain)N=527,529,275,236 | 699 Titers |
| B246_R357 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | Baseline (5/99 strain) N=551,537,280,275 | 1.28 Titers |
| B246_R357 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | post vaccination (44/76-SL) N=525,534,273,253 | 113 Titers |
| B246_R357 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | Baseline (NZ98/254 strain)N=554,543,283,278 | 1.08 Titers |
| B246_R357 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | Baseline (44/76-SL strain) N=556,548,285,277 | 1.36 Titers |
| B+R234 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | post vaccination (NZ98/254 strain)N=30,534,274,257 | 11 Titers |
| B+R234 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | post vaccination (44/76-SL) N=525,534,273,253 | 82 Titers |
| B+R234 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | Baseline (5/99 strain) N=551,537,280,275 | 1.19 Titers |
| B+R234 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | Baseline (44/76-SL strain) N=556,548,285,277 | 1.34 Titers |
| B+R234 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | post vaccination (5/99 strain)N=527,529,275,236 | 325 Titers |
| B+R234 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | Baseline (NZ98/254 strain)N=554,543,283,278 | 1.06 Titers |
| R234 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | Baseline (5/99 strain) N=551,537,280,275 | 1.24 Titers |
| R234 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | post vaccination (44/76-SL) N=525,534,273,253 | 1.16 Titers |
| R234 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | Baseline (NZ98/254 strain)N=554,543,283,278 | 1.07 Titers |
| R234 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | Baseline (44/76-SL strain) N=556,548,285,277 | 1.28 Titers |
| R234 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | post vaccination (NZ98/254 strain)N=30,534,274,257 | 1.11 Titers |
| R234 | Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | post vaccination (5/99 strain)N=527,529,275,236 | 1.25 Titers |
Secondary
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| B+R246 | Non-inferiority of Immune Response to Acellular Pertussis Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine. | Pertactin | 92 Percentages of subjects |
| B+R246 | Non-inferiority of Immune Response to Acellular Pertussis Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine. | FHA | 94 Percentages of subjects |
| B+R246 | Non-inferiority of Immune Response to Acellular Pertussis Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine. | PT | 97 Percentages of subjects |
| B246_R357 | Non-inferiority of Immune Response to Acellular Pertussis Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine. | FHA | 95 Percentages of subjects |
| B246_R357 | Non-inferiority of Immune Response to Acellular Pertussis Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine. | Pertactin | 95 Percentages of subjects |
| B246_R357 | Non-inferiority of Immune Response to Acellular Pertussis Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine. | PT | 98 Percentages of subjects |
Comparison: Non-inferiority of immune responses against Pertussis antigen FHA when routine vaccine was administered concomitantly with rMenB+OMV NZ vaccine to when only routine vaccines were administered.95% CI: [-5, 4]Miettinen and Nurminen method
Comparison: Non-inferiority of immune responses against Pertussis antigen pertactin antigen when routine vaccine was administered concomitantly with rMenB+OMV NZ vaccine to when only routine vaccines were administered.95% CI: [-7, 2]Miettinen and Nurminen method
Comparison: Non-inferiority of immune responses against Pertussis antigen PT when routine vaccine was administered concomitantly with rMenB+OMV NZ vaccine to when only routine vaccines were administered.95% CI: [-4, 2]Miettinen and Nurminen method
Secondary
Non-inferiority of Immune Response to Diphtheria and Tetanus 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 with antibody concentrations ≥0.1 IU/mL against Diphtheria and Tetanus antigens as measured by enzyme-linked immunosorbent assay.
Time frame: One month after 3rd vaccination
Population: All subjects in the Full Analysis Set/MITT population who received all the relevant doses of vaccine correctly, and provided evaluable serum samples at the relevant time points, and had no major protocol violation as defined prior to analysis: Per Protocol (PP) Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| B+R246 | Non-inferiority of Immune Response to Diphtheria and Tetanus Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine | Baseline (Diphtheria) | 25 Percentages of subjects |
| B+R246 | Non-inferiority of Immune Response to Diphtheria and Tetanus Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine | 1 month after 3rd vaccination(Diphtheria)N=261,232 | 100 Percentages of subjects |
| B+R246 | Non-inferiority of Immune Response to Diphtheria and Tetanus Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine | Baseline (Tetanus) | 81 Percentages of subjects |
| B+R246 | Non-inferiority of Immune Response to Diphtheria and Tetanus Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine | 1 month after 3rd vaccination (Tetanus)N=261,232 | 100 Percentages of subjects |
| B246_R357 | Non-inferiority of Immune Response to Diphtheria and Tetanus Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine | 1 month after 3rd vaccination (Tetanus)N=261,232 | 100 Percentages of subjects |
| B246_R357 | Non-inferiority of Immune Response to Diphtheria and Tetanus Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine | Baseline (Diphtheria) | 21 Percentages of subjects |
| B246_R357 | Non-inferiority of Immune Response to Diphtheria and Tetanus Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine | Baseline (Tetanus) | 86 Percentages of subjects |
| B246_R357 | Non-inferiority of Immune Response to Diphtheria and Tetanus Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine | 1 month after 3rd vaccination(Diphtheria)N=261,232 | 100 Percentages of subjects |
Comparison: Non-inferiority of immune responses against Diphtheria antigen when routine vaccine was administered concomitantly with rMenB+OMV NZ vaccine to when only routine vaccines were administered.95% CI: [-1, 2]Miettinen and Nurminen method
Comparison: Non-inferiority of immune response to Tetanus antigens when routine vaccines are administered concomitantly with rMen+OMV NZ vaccine.95% CI: [-1, 2]Miettinen and Nurminen
Secondary
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
Population: Analysis was done on the per-protocol population i.e all subjects in the MITT population who received all the relevant doses of vaccine correctly, provided evaluable serum samples at the relevant time points and had no major protocol violation as defined prior to analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| B+R246 | Non-inferiority of Immune Response to rMenB+OMV NZ Vaccination When Administered Concomitantly With Routine Infant Vaccines at 2,4,6 Months of Age | Baseline(5/99 strain)N=511,537 | 6 Percentages of subjects |
| B+R246 | Non-inferiority of Immune Response to rMenB+OMV NZ Vaccination When Administered Concomitantly With Routine Infant Vaccines at 2,4,6 Months of Age | 1 month post 3rd vaccination(5/99strain)N=527,529 | 100 Percentages of subjects |
| B+R246 | Non-inferiority of Immune Response to rMenB+OMV NZ Vaccination When Administered Concomitantly With Routine Infant Vaccines at 2,4,6 Months of Age | Baseline(NZ98/254 strain)N=554,543 | 3 Percentages of subjects |
| B+R246 | Non-inferiority of Immune Response to rMenB+OMV NZ Vaccination When Administered Concomitantly With Routine Infant Vaccines at 2,4,6 Months of Age | Baseline(44/76-SL strain) | 8 Percentages of subjects |
| B+R246 | Non-inferiority of Immune Response to rMenB+OMV NZ Vaccination When Administered Concomitantly With Routine Infant Vaccines at 2,4,6 Months of Age | 1 month post 3rd vaccination(44/76-SL)N=525,534 | 100 Percentages of subjects |
| B+R246 | Non-inferiority of Immune Response to rMenB+OMV NZ Vaccination When Administered Concomitantly With Routine Infant Vaccines at 2,4,6 Months of Age | 1 month post 3rd vaccination(NZ98/254 )N=530,534 | 79 Percentages of subjects |
| B246_R357 | Non-inferiority of Immune Response to rMenB+OMV NZ Vaccination When Administered Concomitantly With Routine Infant Vaccines at 2,4,6 Months of Age | 1 month post 3rd vaccination(NZ98/254 )N=530,534 | 87 Percentages of subjects |
| B246_R357 | Non-inferiority of Immune Response to rMenB+OMV NZ Vaccination When Administered Concomitantly With Routine Infant Vaccines at 2,4,6 Months of Age | Baseline(5/99 strain)N=511,537 | 7 Percentages of subjects |
| B246_R357 | Non-inferiority of Immune Response to rMenB+OMV NZ Vaccination When Administered Concomitantly With Routine Infant Vaccines at 2,4,6 Months of Age | 1 month post 3rd vaccination(44/76-SL)N=525,534 | 100 Percentages of subjects |
| B246_R357 | Non-inferiority of Immune Response to rMenB+OMV NZ Vaccination When Administered Concomitantly With Routine Infant Vaccines at 2,4,6 Months of Age | 1 month post 3rd vaccination(5/99strain)N=527,529 | 99 Percentages of subjects |
| B246_R357 | Non-inferiority of Immune Response to rMenB+OMV NZ Vaccination When Administered Concomitantly With Routine Infant Vaccines at 2,4,6 Months of Age | Baseline(NZ98/254 strain)N=554,543 | 1 Percentages of subjects |
| B246_R357 | Non-inferiority of Immune Response to rMenB+OMV NZ Vaccination When Administered Concomitantly With Routine Infant Vaccines at 2,4,6 Months of Age | Baseline(44/76-SL strain) | 7 Percentages of subjects |
Comparison: Non-inferiority of immune responses against 44/76-SL strain when rMenB+OMV NZ vaccine was administered concomitantly with routine infant vaccines as compared to when rMenB+OMV NZ vaccine and routine vaccines were given separately.95% CI: [-1, 1]Miettinen and Nurminen method
Comparison: Non-inferiority of immune responses against 5/99 strain when rMenB+OMV NZ vaccine was administered concomitantly with routine infant vaccines as compared to when rMenB+OMV NZ vaccine and routine vaccines were given separately.95% CI: [-1, 1]Miettinen and Nurminen method
Comparison: Non-inferiority of immune responses against NZ98/254 strain when rMenB+OMV NZ vaccine was administered concomitantly with routine infant vaccines as compared to when rMenB+OMV NZ vaccine and routine vaccines were given separately.95% CI: [-12, -4]Miettinen and Nurminen method
Secondary
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
Population: PP Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| B+R246 | Percentage of Subjects With 4-fold Rise in hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | 44/76-SL strain (N=501,507,262,236) | 97 Percentages of subjects |
| B+R246 | Percentage of Subjects With 4-fold Rise in hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | NZ98/254 strain (N=504,503,258,238) | 66 Percentages of subjects |
| B+R246 | Percentage of Subjects With 4-fold Rise in hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | 5/99 strain (N=497,494,257,217) | 99 Percentages of subjects |
| B246_R357 | Percentage of Subjects With 4-fold Rise in hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | 44/76-SL strain (N=501,507,262,236) | 99 Percentages of subjects |
| B246_R357 | Percentage of Subjects With 4-fold Rise in hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | NZ98/254 strain (N=504,503,258,238) | 78 Percentages of subjects |
| B246_R357 | Percentage of Subjects With 4-fold Rise in hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | 5/99 strain (N=497,494,257,217) | 99 Percentages of subjects |
| B+R234 | Percentage of Subjects With 4-fold Rise in hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | 5/99 strain (N=497,494,257,217) | 100 Percentages of subjects |
| B+R234 | Percentage of Subjects With 4-fold Rise in hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | 44/76-SL strain (N=501,507,262,236) | 98 Percentages of subjects |
| B+R234 | Percentage of Subjects With 4-fold Rise in hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | NZ98/254 strain (N=504,503,258,238) | 69 Percentages of subjects |
| R234 | Percentage of Subjects With 4-fold Rise in hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | NZ98/254 strain (N=504,503,258,238) | 3 Percentages of subjects |
| R234 | Percentage of Subjects With 4-fold Rise in hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | 44/76-SL strain (N=501,507,262,236) | 1 Percentages of subjects |
| R234 | Percentage of Subjects With 4-fold Rise in hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | 5/99 strain (N=497,494,257,217) | 3 Percentages of subjects |
Secondary
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
Population: PP Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| B+R246 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Post vaccination(NZ98/254 strain)N=530,534,274,257 | 67 Percentages of subjects |
| B+R246 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Baseline(NZ98/254 strain)N=554,543,283,278 | 1 Percentages of subjects |
| B+R246 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Post vaccination (5/99 strain)N=527,529,275,236 | 100 Percentages of subjects |
| B+R246 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Post vaccination (44/76-SL)N=525,534,273,253 | 99 Percentages of subjects |
| B+R246 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Baseline (44/76-SL strain)N=556,548,285,277 | 4 Percentages of subjects |
| B+R246 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Baseline (5/99 strain)N=551,537,280,275 | 4 Percentages of subjects |
| B246_R357 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Baseline (5/99 strain)N=551,537,280,275 | 3 Percentages of subjects |
| B246_R357 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Baseline (44/76-SL strain)N=556,548,285,277 | 3 Percentages of subjects |
| B246_R357 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Post vaccination (44/76-SL)N=525,534,273,253 | 100 Percentages of subjects |
| B246_R357 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Post vaccination (5/99 strain)N=527,529,275,236 | 99 Percentages of subjects |
| B246_R357 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Baseline(NZ98/254 strain)N=554,543,283,278 | 1 Percentages of subjects |
| B246_R357 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Post vaccination(NZ98/254 strain)N=530,534,274,257 | 79 Percentages of subjects |
| B+R234 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Post vaccination (5/99 strain)N=527,529,275,236 | 100 Percentages of subjects |
| B+R234 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Baseline (5/99 strain)N=551,537,280,275 | 2 Percentages of subjects |
| B+R234 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Post vaccination (44/76-SL)N=525,534,273,253 | 99 Percentages of subjects |
| B+R234 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Baseline(NZ98/254 strain)N=554,543,283,278 | 1 Percentages of subjects |
| B+R234 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Baseline (44/76-SL strain)N=556,548,285,277 | 4 Percentages of subjects |
| B+R234 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Post vaccination(NZ98/254 strain)N=530,534,274,257 | 69 Percentages of subjects |
| R234 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Baseline (44/76-SL strain)N=556,548,285,277 | 2 Percentages of subjects |
| R234 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Post vaccination (5/99 strain)N=527,529,275,236 | 3 Percentages of subjects |
| R234 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Post vaccination(NZ98/254 strain)N=530,534,274,257 | 2 Percentages of subjects |
| R234 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Baseline (5/99 strain)N=551,537,280,275 | 4 Percentages of subjects |
| R234 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Baseline(NZ98/254 strain)N=554,543,283,278 | 0.1 Percentages of subjects |
| R234 | Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | Post vaccination (44/76-SL)N=525,534,273,253 | 2 Percentages of subjects |