Meningitis, Meningococcal Infection
Conditions
Keywords
vaccine, infants, healthy, meningitis, meningococcal
Brief summary
The primary objective of this phase 3b study is to evaluate the safety and tolerability of Novartis MenACWY conjugate vaccine when administered with routine infant vaccinations to healthy infants
Interventions
BIOLOGICALMenACWY-CRM197
Four 0.5mL vaccinations of MenACWY-CRM197 conjugate vaccine was administered by intramuscular injection at 2, 4, 6 and 12 months of age.
BIOLOGICALDTaP (Diptheria, Tetanus, Pertussis) Vaccine
Four vaccinations of DTaP (Diptheria, Tetanus, Pertussis) was administered at 2, 4, 6, and 15 months of age.
BIOLOGICALHib (Haemophilus influenza b) Vaccine
Four vaccinations of Hib (Haemophilus influenza b) vaccine was administered at 2, 4, 6 and 15 months of age.
BIOLOGICALIPV (Inactivated Polio Vaccine) Vaccine
Three vaccinations of IPV (Inactivated Polio Vaccine) was administered at 2, 4, and 6 months of age.
BIOLOGICALPneumococcal conjugate Vaccine
Four vaccinations of Pneumococcal conjugate vaccine was administered at 2, 4, 6 and 12 months of age.
BIOLOGICALMMR (Measles, Mumps, and Rubella) Vaccine
One vaccination of MMR (Measles, Mumps, and Rubella) was administered at 12 months of age.
BIOLOGICALVaricella Vaccine
One vaccination of Varicella vaccine was administered at 12 months of age.
BIOLOGICALHepatitis A Virus
One vaccination of Hepatitis A Virus vaccine was administered at 12 months of age.
Sponsors
Novartis Vaccines
Novartis
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 (aged 55 - 89 days); babies must have been born after a full-term pregnancy with an estimated gestation age ≥37 weeks and a birth weight ≥2.5 kg * for whom a parent/legal representative has given written informed consent after the nature of the study has been explained; * who are available for all visits scheduled in the study; * who are in good health as determined by medical history and physical assessment.
Exclusion criteria
* who previously received any meningococcal vaccine or D, T, P, IPV or OPV, H influenzae type b (Hib) or Pneumococcus; prior doses of BCG (one) and/or HBV (two) are permitted * who have a previous confirmed or suspected disease caused by N meningitidis, C diphtheriae, C tetani, Poliovirus, Hepatitis B, Hib, Pneumococcus or B pertussis (history of laboratory confirmed, or clinical condition of paroxysmal cough for a period of longer than or equal to 2 weeks associated with apnea or whooping); * who have had household contact with and/or intimate exposure to an individual with laboratory confirmed N meningitidis (serogroups A, C, W135, or Y), B pertussis, Hib, C diphtheriae, Polio, or pneumococcal infection at any time since birth; * who have a history of anaphylactic shock, asthma, urticaria or other allergic reaction after previous vaccinations or known hypersensitivity to any vaccine component; * who have experienced significant acute or chronic infection within the previous 7 days or have experienced fever (axillary temperature ≥ 38.0°C \[100.4°F\]) within the previous 3 days; * who have any present or suspected serious acute (e.g. leukemia, lymphomas), or chronic disease (e.g., with signs of cardiac disease, renal failure, severe malnutrition, or insulin dependent diabetes), or progressive neurological disease, or a genetic anomaly/known cytogenic disorders (e.g., Down's syndrome); * who have a known or suspected autoimmune disease or persistent impairment/alteration of immune function resulting from (for example): 1. receipt of any immunosuppressive therapy at any time since birth 2. receipt of immunostimulants at any time since birth 3. receipt of any systemic corticosteroid since birth; * who have a suspected or known HIV infection or HIV related disease; * who have ever received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation; * who have a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time; * who have any history of seizure; * who with their parents/legal representatives are planning to leave the area of the study site before the end of the study period; * who have any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives; * who have received any investigational agents or vaccines since birth or who expect to receive an investigational agent or vaccine prior to the completion of the study. * who are relatives of site research staff working on this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentages of Subjects With At Least One Severe Systemic Reaction After Any Vaccination | 15 minutes to Day 7 after any vaccination administered at 2, 4, 6 and 12 months of age | To compare the percentages of subjects who reported at least one severe systemic reaction after any vaccination of MenACWY-CRM197 (detailed) plus routine vaccines (detailed) group to that observed in the routine vaccines alone (detailed) group administered at 2, 4, 6, and 12 months of age. Detailed - infants who provided reactogenicity and all Adverse Events (AEs) for 7 days, Serious Adverse Events (SAEs) and medically attended AEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentages of Subjects With At Least One Serious Adverse Event During the Entire Study Period | Day 1 (2 months of age) to 18 months of age | To compare the percentages of subjects presenting at least one serious adverse event (SAE) through 6 months post-final dose in subjects who received MenACWY-CRM197 vaccine concomitantly with routine vaccinations to the percentages of subjects who received routine vaccinations alone. |
| Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | 15 minutes to Day 7 | To compare the percentage of subjects who reported local and systemic solicited adverse events from day 1 to day 7 after each vaccination with MenACWY-CRM197 given concomitantly with routine vaccinations to the routine vaccinations alone group. |
| Number of Subjects Who Reported Unsolicited Adverse Events After Any Vaccination | Day 1 (2 months of age) to 18 months of age | Safety data with medically attended events were collected throughout the study in the non-detailed safety groups and from Day 8 onwards for the detailed safety groups. |
Countries
China, Costa Rica, Guatemala, Panama, Peru, United States
Participant flow
Pre-assignment details
All subjects enrolled were included in the trial.
Participants by arm
| Arm | Count |
|---|---|
| MenACWY-CRM197 + Routine Vaccines (Non-Detailed) Infants received one vaccination of MenACWY-CRM197 vaccine at 2, 4, 6 and 12 months of age and one vaccination of routine vaccines (according to the local vaccination schedule) - DTaP: 2, 4, 6, 15 months, IPV: 2, 4, 6, months, Hib: 2, 4, 6, 15 months, Pneumococcal conjugate: 2, 4, 6, 12 months, MMR: 12 months.
Routine vaccines given to subjects in these arms will be consistent with the US ACIP recommended vaccines.
Non-Detailed - subjects who only provided SAEs and medically attended AEs. | 4,363 |
| Routine Vaccines (Non-Detailed) Infants received one vaccination of routine vaccines (according to the local vaccination schedule) - DTaP: 2, 4, 6, 15 months, IPV: 2, 4, 6 months, Hib: 2, 4, 6, 15 months, Pneumococcal conjugate: 2, 4, 6, 12 months, MMR: 12 months.
Routine vaccines given to subjects in these arms will be consistent with the US ACIP recommended vaccines.
Non-Detailed - subjects who only provided SAEs and medically attended AEs. | 1,483 |
| MenACWY-CRM197 + Routine Vaccines (Detailed) Infants received one vaccination of MenACWY-CRM197 vaccine at 2, 4, 6 and 12 months of age and one vaccination of routine vaccines (according to the local vaccination schedule) - DTaP: 2, 4, 6, 15 months, IPV: 2, 4, 6, months, Hib: 2, 4, 6, 15 months, Pneumococcal conjugate: 2, 4, 6, 12 months, MMR, Varicella, Hepatitis A: 12 months. HBV and rotavirus vaccines should be administered according to ACIP guidelines during the first year of life.
Routine vaccines given to subjects in these arms will be consistent with the US ACIP recommended vaccines.
Detailed - subjects who provided Reactogenicity and all AEs for 7 days, SAEs and medically attended AEs. | 1,409 |
| Routine Vaccines (Detailed) Infants received one vaccination of routine vaccines (according to the local vaccination schedule) - DTaP: 2, 4, 6, 15 months, IPV: 2, 4, 6 months, Hib: 2, 4, 6, 15 months, Pneumococcal conjugate: 2, 4, 6, 12 months, MMR, Varicella, and Hepatitis A: 12 months. HBV and rotavirus vaccines should be administered according to ACIP guidelines during the first year of life.
Routine vaccines given to subjects in these arms will be consistent with the US ACIP recommended vaccines.
Detailed - subjects who provided Reactogenicity and all AEs for 7 days, SAEs and medically attended AEs. | 489 |
| Total | 7,744 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Administrative Reason | 113 | 35 | 66 | 26 |
| Overall Study | Adverse Event | 25 | 5 | 11 | 2 |
| Overall Study | Death | 6 | 0 | 1 | 0 |
| Overall Study | Inappropriate Enrollment | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 217 | 66 | 90 | 34 |
| Overall Study | Protocol Violation | 34 | 24 | 26 | 9 |
| Overall Study | Withdrawal by Subject | 119 | 31 | 76 | 35 |
Baseline characteristics
| Characteristic | MenACWY-CRM197 + Routine Vaccines (Non-Detailed) | Routine Vaccines (Non-Detailed) | MenACWY-CRM197 + Routine Vaccines (Detailed) | Routine Vaccines (Detailed) | Total |
|---|---|---|---|---|---|
| Age Continuous | 64.9 Days STANDARD_DEVIATION 7.4 | 64.7 Days STANDARD_DEVIATION 7.1 | 65.5 Days STANDARD_DEVIATION 6.5 | 65.2 Days STANDARD_DEVIATION 6.3 | 65.0 Days STANDARD_DEVIATION 7.1 |
| Sex: Female, Male Female | 2135 Participants | 703 Participants | 716 Participants | 232 Participants | 3786 Participants |
| Sex: Female, Male Male | 2228 Participants | 780 Participants | 693 Participants | 257 Participants | 3958 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4,701 / 5,760 | 1,600 / 1,968 |
| serious Total, serious adverse events | 354 / 5,760 | 114 / 1,968 |
Outcome results
Primary
Percentages of Subjects With At Least One Severe Systemic Reaction After Any Vaccination
To compare the percentages of subjects who reported at least one severe systemic reaction after any vaccination of MenACWY-CRM197 (detailed) plus routine vaccines (detailed) group to that observed in the routine vaccines alone (detailed) group administered at 2, 4, 6, and 12 months of age. Detailed - infants who provided reactogenicity and all Adverse Events (AEs) for 7 days, Serious Adverse Events (SAEs) and medically attended AEs.
Time frame: 15 minutes to Day 7 after any vaccination administered at 2, 4, 6 and 12 months of age
Population: Analysis was done on As Treated Safety Population - Subjects who received at least one study dose and provided postbaseline safety data, and that subjects would be included in the group for the vaccination actually received (i.e., analyzed as treated).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects With At Least One Severe Systemic Reaction After Any Vaccination | 16 Percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects With At Least One Severe Systemic Reaction After Any Vaccination | 13 Percentages of subjects |
Comparison: MenACWY-CRM 197 administered concomitantly with routine vaccines was considered noninferior to routine vaccines alone with respect to severe systemic reactions if the upper limit of the 2-sided 95% CI of the difference (MenACWY-CRM197 vaccine plus routine vaccines group minus routine vaccines only group) in the proportion of subjects experiencing at least one severe systemic reaction during the first 7 days (days 1-7) after any vaccination was \<6%.95% CI: [-0.8, 6.4]Miettinen and Nurminen
Secondary
Number of Subjects Who Reported Unsolicited Adverse Events After Any Vaccination
Safety data with medically attended events were collected throughout the study in the non-detailed safety groups and from Day 8 onwards for the detailed safety groups.
Time frame: Day 1 (2 months of age) to 18 months of age
Population: Analysis was done on as treated safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Number of Subjects Who Reported Unsolicited Adverse Events After Any Vaccination | Any AE | 4848 Subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Number of Subjects Who Reported Unsolicited Adverse Events After Any Vaccination | AEs Leading to Premature Withdrawals | 44 Subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Number of Subjects Who Reported Unsolicited Adverse Events After Any Vaccination | Any SAE-Total | 354 Subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Number of Subjects Who Reported Unsolicited Adverse Events After Any Vaccination | Deaths | 7 Subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Number of Subjects Who Reported Unsolicited Adverse Events After Any Vaccination | Possibly or Probably Related AEs | 520 Subjects |
| Routine Vaccines (Detailed) | Number of Subjects Who Reported Unsolicited Adverse Events After Any Vaccination | Deaths | 1 Subjects |
| Routine Vaccines (Detailed) | Number of Subjects Who Reported Unsolicited Adverse Events After Any Vaccination | Any AE | 1659 Subjects |
| Routine Vaccines (Detailed) | Number of Subjects Who Reported Unsolicited Adverse Events After Any Vaccination | Possibly or Probably Related AEs | 2 Subjects |
| Routine Vaccines (Detailed) | Number of Subjects Who Reported Unsolicited Adverse Events After Any Vaccination | AEs Leading to Premature Withdrawals | 8 Subjects |
| Routine Vaccines (Detailed) | Number of Subjects Who Reported Unsolicited Adverse Events After Any Vaccination | Any SAE-Total | 114 Subjects |
Secondary
Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination
To compare the percentage of subjects who reported local and systemic solicited adverse events from day 1 to day 7 after each vaccination with MenACWY-CRM197 given concomitantly with routine vaccinations to the routine vaccinations alone group.
Time frame: 15 minutes to Day 7
Population: Analysis was done on as treated safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Erythema (N=1095, 349) | 21 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Tenderness (N=1301, 446) | 46 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Erythema (N=1297, 445) | 17 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Induration (N=1297, 446) | 8 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Any Local (4 month vaccination) (N=1262, 420) | 46 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Tenderness (N=1255, 418) | 37 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Erythema (N=1257, 417) | 19 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Induration (N=1257, 417) | 9 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Any Local (6 month vaccination) (N=1120, 374) | 41 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Tenderness (N=1106, 372) | 30 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Erythema (N=1104, 370) | 22 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Induration (N=1107, 370) | 9 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Any Local (12 month vaccination) (N=1102, 355) | 47 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Tenderness (N=1098, 353) | 39 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Any Local (2 month vaccination) (N=1313, 451) | 53 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Induration (N=1095, 351) | 10 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Any Systemic (2 month vaccination) (N=1313, 451) | 77 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Rash (N=1296, 446) | 3 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Change in Eating Habits (N=1289, 446) | 23 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Sleepiness (N=1297, 447) | 52 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Persistent crying (N=1299,46) | 42 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Irritability (N=1300, 446) | 59 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Vomiting (N=1298, 446) | 10 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Diarrhea (N=1299, 446) | 16 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Fever ( ≥ 38°C) (N=1297, 446) | 3 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Analges.Antipyr.Meds (N=1302, 448) | 66 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Any Systemic (4 month vaccination) (N=1262, 420) | 65 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Rash (N=1253, 416) | 3 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Change in Eating Habits (N=1245, 414) | 18 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Sleepiness (N=1253, 416) | 38 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Persistent Crying (N=1254, 417) | 31 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Irritability (N=1254, 416) | 50 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Vomiting (N=1254, 416) | 8 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Diarrhea (N=1255, 416) | 11 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Fever ( ≥ 38°C) (N=1251, 416) | 4 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Analges.Antipyr.Meds (N=1254, 416) | 58 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Any Systemic (6 month vaccination) (N=1120, 374) | 58 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Rash (N=1101, 367) | 3 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Change in Eating Habits (N=1094, 367) | 17 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Sleepiness (N=1104, 367) | 31 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Persistent Crying (N=1103, 368) | 26 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Irritability (N=1104, 369) | 46 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Vomiting (N=1106, 369) | 6 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Diarrhea (N=1102, 369) | 8 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Fever ( ≥ 38°C) (N=1108, 368) | 7 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Analges.Antipyr.Meds (N=1103, 370) | 53 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Any Systemic (12 month vaccination) (N=1102, 355) | 63 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Rash (N=1093, 353) | 4 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Change in Eating Habits (N=1089, 348) | 18 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Sleepiness (N=1096, 353) | 30 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Persistent Crying (N=1094, 353) | 28 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Irritability (N=1094, 354) | 50 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Vomiting (N=1094, 353) | 5 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Diarrhea (N=1094, 353) | 12 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Fever ( ≥ 38°C) (N=1092, 353) | 9 percentages of subjects |
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Analges.Antipyr.Meds (N=1095, 354) | 49 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Vomiting (N=1094, 353) | 4 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Any Local (2 month vaccination) (N=1313, 451) | 56 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Change in Eating Habits (N=1245, 414) | 17 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Tenderness (N=1301, 446) | 49 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Vomiting (N=1106, 369) | 4 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Erythema (N=1297, 445) | 21 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Sleepiness (N=1253, 416) | 37 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Induration (N=1297, 446) | 16 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Sleepiness (N=1096, 353) | 29 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Any Local (4 month vaccination) (N=1262, 420) | 54 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Persistent Crying (N=1254, 417) | 28 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Tenderness (N=1255, 418) | 42 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Diarrhea (N=1102, 369) | 6 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Erythema (N=1257, 417) | 29 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Irritability (N=1254, 416) | 48 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Induration (N=1257, 417) | 17 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Fever ( ≥ 38°C) (N=1092, 353) | 8 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Any Local (6 month vaccination) (N=1120, 374) | 50 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Vomiting (N=1254, 416) | 6 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Tenderness (N=1106, 372) | 37 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Fever ( ≥ 38°C) (N=1108, 368) | 6 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Erythema (N=1104, 370) | 29 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Diarrhea (N=1255, 416) | 8 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Induration (N=1107, 370) | 19 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Persistent Crying (N=1094, 353) | 24 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Any Local (12 month vaccination) (N=1102, 355) | 57 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Fever ( ≥ 38°C) (N=1251, 416) | 6 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Tenderness (N=1098, 353) | 50 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Analges.Antipyr.Meds (N=1103, 370) | 49 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Erythema (N=1095, 349) | 30 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Analges.Antipyr.Meds (N=1254, 416) | 55 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Injection Site Induration (N=1095, 351) | 23 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Diarrhea (N=1094, 353) | 9 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Any Systemic (2 month vaccination) (N=1313, 451) | 73 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Any Systemic (6 month vaccination) (N=1120, 374) | 54 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Rash (N=1296, 446) | 3 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Any Systemic (12 month vaccination) (N=1102, 355) | 62 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Change in Eating Habits (N=1289, 446) | 24 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Rash (N=1101, 367) | 3 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Sleepiness (N=1297, 447) | 52 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Irritability (N=1094, 354) | 49 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Persistent crying (N=1299,46) | 40 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Change in Eating Habits (N=1094, 367) | 14 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Irritability (N=1300, 446) | 59 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Rash (N=1093, 353) | 5 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Vomiting (N=1298, 446) | 9 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Sleepiness (N=1104, 367) | 29 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Diarrhea (N=1299, 446) | 11 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Analges.Antipyr.Meds (N=1095, 354) | 50 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Fever ( ≥ 38°C) (N=1297, 446) | 2 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Persistent Crying (N=1103, 368) | 20 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Analges.Antipyr.Meds (N=1302, 448) | 60 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Change in Eating Habits (N=1089, 348) | 16 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Any Systemic (4 month vaccination) (N=1262, 420) | 63 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Irritability (N=1104, 369) | 41 percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination | Rash (N=1253, 416) | 4 percentages of subjects |
Secondary
Percentages of Subjects With At Least One Serious Adverse Event During the Entire Study Period
To compare the percentages of subjects presenting at least one serious adverse event (SAE) through 6 months post-final dose in subjects who received MenACWY-CRM197 vaccine concomitantly with routine vaccinations to the percentages of subjects who received routine vaccinations alone.
Time frame: Day 1 (2 months of age) to 18 months of age
Population: Analysis was done on as treated safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MenACWY-CRM197 + Routine Vaccines (Detailed) | Percentages of Subjects With At Least One Serious Adverse Event During the Entire Study Period | 6 Percentages of subjects |
| Routine Vaccines (Detailed) | Percentages of Subjects With At Least One Serious Adverse Event During the Entire Study Period | 6 Percentages of subjects |
Comparison: MenACWY-CRM 197 administered concomitantly with routine vaccines was considered non inferior to routine vaccines alone with respect to serious adverse events if the upper limit of the 2-sided 95% CI of the difference (MenACWY vaccine plus routine vaccines group minus routine vaccines only group) of the proportion of subjects experiencing at least one serious adverse event was \<5%.95% CI: [-0.9, 1.5]Miettinen and Nurminen
Comparison: MenACWY-CRM 197 administered concomitantly with routine vaccines was considered non inferior to routine vaccines alone with respect to serious adverse events if the upper limit of the 2-sided 95% CI of the difference (MenACWY vaccine plus routine vaccines group minus routine vaccines only group) of the proportion of subjects experiencing at least one serious adverse event was \<5%.95% CI: [-0.8, 1.3]Miettinen and Nurminen