A Study to Evaluate the Safety and Immunogenicity of 4 Do... | NCT01000311

Label	Type	Description	Intervention Names
MenACWY-CRM + Routine Vaccines	Experimental	Infants received 3 doses of MenACWY-CRM at 2, 4 and 6 months as a infant series vaccination and a toddler dose at 12 months of age. Infants also received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.	Biological: MenACWY-CRM Biological: DTaP-IPV/Hib Biological: HBV Biological: PCV Biological: MMR
Routine Vaccines	Experimental	Infants received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months. In addition subjects were offered a dose of MenACWY-CRM at 18 months as a benefit of participating in this study. However, blood was not drawn for immunogenicity analysis after this dose.	Biological: DTaP-IPV/Hib Biological: HBV Biological: PCV Biological: MMR

Name	Type	Description	Arm Group Labels	Other Names
MenACWY-CRM	Biological	One dose (0.5 mL) of MenACWY conjugate vaccine supplied as an extemporaneous mixing just before injection of the lyophilized component (MenA) reconstituted with the liquid component (MenCWY) was administered at 2, 4, 6 and 12 months of age as IM injections in the anterolateral area of the thigh.

Measure	Description	Time Frame
Percentage of Subjects With hSBA Titer ≥1:8 Against Serogroup A, C, W and Y One Month After Toddler Vaccination of MenACWY-CRM	Immunogenicity was measured as the percentage of subjects who achieved hSBA titer ≥1:8 against meningococcal serogroup A, C, W and Y, evaluated by serum bactericidal assay using human complement (hSBA), at baseline and one month after toddler dose of MenACWY-CRM administered at 12 months of age. The immune response was considered sufficient if the lower limit of the two-sided 95% confidence intervals (CIs) for the percentage of subjects with hSBA titer ≥1:8, at one month after toddler vaccination, was greater than 85% for the serogroup C, W, or Y and greater than 80% for the serogroup A.	Baseline and one month after fourth-dose of MenACWY-CRM

Measure	Description	Time Frame
hSBA Geometric Mean Titers Against Serogroup A, C, W and Y One Month After Toddler Vaccination of MenACWY-CRM	Immunogenicity was measured as the hSBA geometric mean titers (GMTs) directed against meningococcal serogroup A, C, W and Y, at baseline and one month after toddler dose of MenACWY-CRM administered at 12 months of age.	Baseline and one month after fourth-dose of MenACWY-CRM

Facility	Status	City	State	ZIP	Country	Contacts
37 Alabama Clinical Therapeutics LLC 52 Medical Park East Drive Suite 203		Birmingham	Alabama	35235	United States

ID	Title	Description
FG000	MenACWY-CRM + Routine Vaccines	Infants received 3 doses of MenACWY-CRM at 2, 4 and 6 months as a infant series vaccination and a toddler dose at 12 months. Infants also received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.
FG001

Type

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Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Subjects With hSBA Titer ≥1:8 Against Serogroup A, C, W and Y One Month After Toddler Vaccination of MenACWY-CRM

Immunogenicity was measured as the percentage of subjects who achieved hSBA titer ≥1:8 against meningococcal serogroup A, C, W and Y, evaluated by serum bactericidal assay using human complement (hSBA), at baseline and one month after toddler dose of MenACWY-CRM administered at 12 months of age.

The immune response was considered sufficient if the lower limit of the two-sided 95% confidence intervals (CIs) for the percentage of subjects with hSBA titer ≥1:8, at one month after toddler vaccination, was greater than 85% for the serogroup C, W, or Y and greater than 80% for the serogroup A.

Analysis was done on the per-protocol (PP) toddler dataset for MenACWY-CRM, i.e. the subjects 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 database lock.

Posted

Number

95% Confidence Interval

Percentage of subjects

Baseline and one month after fourth-dose of MenACWY-CRM

ID	Title	Description
OG000	MenACWY-CRM + Routine Vaccines	Infants received 3 doses of MenACWY-CRM at 2, 4 and 6 months as a infant series vaccination and a toddler dose at 12 months. Infants also received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.
OG001	Routine Vaccines	Infants received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.

Units	Counts
Participants	OG000170 OG001178

Title

Denominators

Categories

Serogroup A - Baseline (N=170,178)

Title	Measurements
	OG0002(0 to 5) OG0011(0.014 to 3)

Serogroup A - Post-4th dose (N=168,175)

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000	The null hypothesis associated with the primary objective was that the immune response was considered sufficient if the lower limit of the two-sided 95% confidence intervals (CIs) for the percentage of subjects with hSBA titer ≥1:8, at one month after 4th dose was greater than 80% for the serogroup A.					Lower limit of 95% confidence interval	83			2-Sided	95	83	93				No	Superiority or Other

Secondary

hSBA Geometric Mean Titers Against Serogroup A, C, W and Y One Month After Toddler Vaccination of MenACWY-CRM

Immunogenicity was measured as the hSBA geometric mean titers (GMTs) directed against meningococcal serogroup A, C, W and Y, at baseline and one month after toddler dose of MenACWY-CRM administered at 12 months of age.

Analysis was performed on the PP toddler dataset for MenACWY-CRM vaccination.

Posted

Geometric Mean

95% Confidence Interval

Titers

Baseline and one month after fourth-dose of MenACWY-CRM

ID	Title	Description
OG000	MenACWY-CRM + Routine Vaccines	Infants received 3 doses of MenACWY-CRM at 2, 4 and 6 months as a infant series vaccination and a toddler dose at 12 months. Infants also received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.
OG001	Routine Vaccines	Infants received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.

Units	Counts
Participants

Secondary

Percentage of Subjects With hSBA Titers ≥1:8, and Four-Fold Increase in hSBA Titers Against Serogroup A, C, W and Y One Month After Three Dose Infant Series Vaccination of MenACWY-CRM

Immunogenicity was measured as the percentage of subjects with hSBA titers ≥1:8 against meningococcal serogroup A, C, W and Y, before (baseline) and one month after 3 infant doses of MenACWY-CRM administered at 2, 4 and 6 months of age.

Percentage of subjects who achieved at least four-fold rise in hSBA titers against serogroup A, C, W and Y was measured one month after 3 infant doses of MenACWY-CRM.

Analysis was performed on the PP dataset of MenACWY-CRM infant vaccination series.

Posted

Number

95% Confidence Interval

Percentage of subjects

Baseline and one month after third infant dose of MenACWY-CRM

ID	Title	Description
OG000	MenACWY-CRM + Routine Vaccines	Infants received 3 doses of MenACWY-CRM at 2, 4 and 6 months as a infant series vaccination and a toddler dose at 12 months. Infants also received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.
OG001	Routine Vaccines	Infants received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.

Secondary

hSBA Geometric Mean Titers Against Serogroup A, C, W and Y One Month After Three Dose Infant Series Vaccination of MenACWY-CRM

Immunogenicity was measured as the hSBA GMTs directed against meningococcal serogroups A, C, W and Y before (baseline) and one month after 3 infants doses of MenACWY-CRM administered at 2, 4 and 6 months of age.

Analysis was performed on the PP dataset of MenACWY-CRM infant vaccination series.

Posted

Geometric Mean

95% Confidence Interval

Titers

Baseline and one month after third infant dose of MenACWY-CRM

ID	Title	Description
OG000	MenACWY-CRM + Routine Vaccines	Infants received 3 doses of MenACWY-CRM at 2, 4 and 6 months as a infant series vaccination and a toddler dose at 12 months. Infants also received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.
OG001	Routine Vaccines	Infants received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.

Units	Counts
Participants

Secondary

Percentage of Subjects With Seroresponse to Routine Concomitant Vaccinations One Month After Infant Series, When Routine Vaccines Are Administered With MenACWY-CRM Compared With When Routine Vaccines Are Given Alone

The immune seroresponse to routine concomitant vaccination was measured as the percentages of subjects with pre-specified cut-off limit of ≥0.1 IU/mL (Diphtheria and Tetanus); ≥0.15 μg/mL (Hib); ≥0.35 μg/mL (Pneumococcal antigens, PnC); and ≥10 mIU/mL (Hepatitis B), evaluated using enzyme-linked immunosorbent assay (ELISA) at one month after 3 doses of infant series vaccination administered at 2, 4 and 6 months of age.

The immune response to pertussis antigens (PT, FHA, Pertactin, FIM) was measured as percentage of subjects with seroresponse (in initially seronegative infants, ≥4 times the lower limit of quantification (LLQ); in initially seropositive infants, at least 4 times prevaccination concentration) by ELISA and percentage of subjects with titer ≥1:8 (Polio types 1, 2, and 3) by neutralization test (NT) one month after 3 doses of infant series vaccination administered at 2, 4 and 6 months of age.

Analysis was performed on the PP concomitant, pertussis and hepatitis B infant populations.

Posted

Number

95% Confidence Interval

Percentage of subjects

One month after third dose of routine infant series vaccination

ID	Title	Description
OG000	MenACWY-CRM + Routine Vaccines	Infants received 3 doses of MenACWY-CRM at 2, 4 and 6 months as a infant series vaccination and a toddler dose at 12 months. Infants also received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.

Secondary

Geometric Mean Concentrations Of Antibodies Against Routine Concomitant Vaccinations One Month After Infant Series, When Routine Vaccines Are Administered With MenACWY-CRM Compared With When Routine Vaccines Are Given Alone

The immune response was measured as the geometric mean concentrations (GMCs) of antibodies directed against diphtheria, tetanus, pertussis (PT, FHA, Pertactin, FIM), hepatitis B, Hib, polio (type 1, 2 and 3) and pneumococcal (PnC 4, 6B, 9V, 14, 18C, 19F and 23F) antigens when routine vaccines are administered concomitantly with MenACWY-CRM compared with when routine vaccines are given alone, one month after 3 doses of infant series vaccination at 2, 4 and 6 months of age.

Analysis was performed on the PP datasets of infants for concomitant, pertussis and hepatitis B vaccinations

Posted

Geometric Mean

95% Confidence Interval

μg/mL

One month after third dose of routine infant series vaccination

ID	Title	Description
OG000	MenACWY-CRM + Routine Vaccines	Infants received 3 doses of MenACWY-CRM at 2, 4 and 6 months as a infant series vaccination and a toddler dose at 12 months. Infants also received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.
OG001	Routine Vaccines	Infants received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.

Secondary

Geometric Mean Concentrations Of Antibodies Against Pneumococcal Antigens One Month After Toddler Vaccination With PCV Administered With MenACWY-CRM Compared With PCV Given Alone

Immunogenicity was measured as the GMCs of anti-pneumococcal antibodies against pneumococcal antigens PnC 4, 6B, 9V, 14, 18C, 19F and 23F, one month after toddler dose of PCV at 12 months of age administered concomitantly with MenACWY-CRM compared with PCV given alone.

Analysis was performed on the PP pneumococcal toddler population.

Posted

Geometric Mean

95% Confidence Interval

μg/mL

One month after PCV toddler vaccination

ID	Title	Description
OG000	MenACWY-CRM + Routine Vaccines	Infants received 3 doses of MenACWY-CRM at 2, 4 and 6 months as a infant series vaccination and a toddler dose at 12 months. Infants also received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.
OG001	Routine Vaccines	Infants received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.

Units	Counts

Secondary

Percentage of Subjects With Anti-pneumococcal Antigen Antibodies ≥0.35 μg/mL One Month After Toddler Vaccination With PCV Administered With MenACWY-CRM Compared With PCV Given Alone

The immune seroresponse was measured as the percentage of subjects with anti-pneumococcal antigen antibodies ≥0.35 μg/mL against pneumococcal antigens PnC 4, 6B, 9V, 14, 18C, 19F and 23F, one month after toddler dose of PCV at 12 months of age when administered concomitantly with MenACWY-CRM compared with PCV given alone.

Analysis was performed on the PP pneumococcal toddler population.

Posted

Number

95% Confidence Interval

Percentage of subjects

One month after PCV toddler vaccination

ID	Title	Description
OG000	MenACWY-CRM + Routine Vaccines	Infants received 3 doses of MenACWY-CRM at 2, 4 and 6 months as a infant series vaccination and a toddler dose at 12 months. Infants also received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.
OG001	Routine Vaccines	Infants received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.

Units

Secondary

Antibody Persistence by Percentage of Subjects With hSBA Titers ≥1:8 Against Serogroup A, C, W and Y, Six Months After Third Infant Vaccination, Prior to MenACWY-CRM Toddler Vaccination

The antibody persistence was measured as the percentage of subjects with hSBA titers ≥1:8 against meningococcal serogroup A, C, W and Y, at baseline and six months after third infant dose of MenACWY-CRM administered at 6 months (12 months of age), before administration of the toddler dose of MenACWY-CRM.

Analysis was performed on the PP toddler dataset for MenACWY-CRM.

Posted

Number

95% Confidence Interval

Percentage of subjects

Baseline and Six months after third infant dose of MenACWY-CRM

ID	Title	Description
OG000	MenACWY-CRM + Routine Vaccines	Infants received 3 doses of MenACWY-CRM at 2, 4 and 6 months as a infant series vaccination and a toddler dose at 12 months. Infants also received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.
OG001	Routine Vaccines	Infants received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.

Units

Secondary

Persistence of hSBA Geometric Mean Titers Against Serogroup A, C, W and Y, Six Months After Third Infant Vaccination, Prior to MenACWY-CRM Toddler Vaccination

The antibody persistence was measured as the hSBA GMTs directed against meningococcal serogroup A, C, W and Y, at baseline and six months after third infant dose of MenACWY-CRM administered at 6 months (12 months of age), before administration of the toddler dose of MenACWY-CRM.

Analysis was performed on the PP toddler dataset for MenACWY-CRM.

Posted

Geometric Mean

95% Confidence Interval

Titers

Baseline and Six months after third infant dose of MenACWY-CRM

ID	Title	Description
OG000	MenACWY-CRM + Routine Vaccines	Infants received 3 doses of MenACWY-CRM at 2, 4 and 6 months as a infant series vaccination and a toddler dose at 12 months. Infants also received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.
OG001	Routine Vaccines	Infants received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.

Units	Counts

Secondary

Percentage of Subjects With Four-fold Increase in hSBA Titers Against Serogroup A, C, W and Y One Month After Toddler Vaccination of MenACWY-CRM

The immune response was measured as the percentage of subjects who achieved four-fold increase in hSBA titers against meningococcal serogroup A, C, W and Y one month after toddler dose of MenACWY-CRM administered at 12 months of age as compared to hSBA titers before the toddler vaccination.

Analysis was performed on the PP toddler dataset for MenACWY-CRM.

Posted

Number

95% Confidence Interval

Percentage of subjects

One month after MenACWY-CRM toddler vaccination

ID	Title	Description
OG000	MenACWY-CRM + Routine Vaccines	Infants received 3 doses of MenACWY-CRM at 2, 4 and 6 months as a infant series vaccination and a toddler dose at 12 months. Infants also received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.
OG001	Routine Vaccines	Infants received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.

Units	Counts

Secondary

Safety of MenACWY-CRM Vaccinations When Administered Concomitantly With Routine Vaccinations

Safety of the study vaccines (MenACWY-CRM and other routine vaccines) was assessed in terms of the number of subjects who reported adverse events (AEs) and/or serious AEs per vaccine group at the following time points: entire study period, after infants vaccination (up to 7 months), between 2- and 4-months, between 4- and 6-months, between 6- and 12-months, between 7- and 12-months, 28 days after 12-month vaccination, and between 29 days after 12-month vaccination and study termination.

Solicited reactions were not collected during this study. The safety analyses also included any AEs observed by study personnel within 15 minutes following vaccination. All AEs and SAEs were judged by the investigator as whether probably related, possibly related, or not related to vaccine.

Analysis was performed on the safety dataset, i.e. all subjects in the exposed population who provided postbaseline safety data

Posted

Number

Number of subjects

From day 1 to 18 months

ID	Title	Description
OG000	MenACWY-CRM + Routine Vaccines	Infants received 3 doses of MenACWY-CRM at 2, 4 and 6 months as a infant series vaccination and a toddler dose at 12 months. Infants also received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.
OG001	Routine Vaccines	Infants received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Laryngomalacia	Congenital, familial and genetic disorders	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected270 at risk
Diarrhoea	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected270 at risk
Gastrointestinal motility disorder	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected270 at risk
Impaired gastric emptying	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected270 at risk
Inguinal Hernia	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected270 at risk
Abscess	Infections and infestations	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0012 events2 affected270 at risk
Bronchiolitis	Infections and infestations	Non-systematic Assessment	EG0004 events4 affected255 at risk EG0012 events2 affected270 at risk
Cellulitis	Infections and infestations	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0012 events2 affected270 at risk
Clostridial infection	Infections and infestations	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected270 at risk
Croup infectious	Infections and infestations	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0013 events3 affected270 at risk
Meningitis enteroviral	Infections and infestations	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected270 at risk
Metapneumovirus infection	Infections and infestations	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected270 at risk
Otitis media	Infections and infestations	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected270 at risk
Pneumonia	Infections and infestations	Non-systematic Assessment	EG0002 events2 affected255 at risk EG0011 events1 affected270 at risk
Pneumonia parainfluenzae viral	Infections and infestations	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected270 at risk
Pneumonia viral	Infections and infestations	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected270 at risk
Pyelonephritis	Infections and infestations	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0011 events1 affected270 at risk
Respiratory syncytial virus bronchiolitis	Infections and infestations	Non-systematic Assessment	EG0003 events3 affected255 at risk EG0012 events2 affected270 at risk
Respiratory tract infection	Infections and infestations	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected270 at risk
Sinusitis	Infections and infestations	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected270 at risk
Subcutaneous abscess	Infections and infestations	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0011 events1 affected270 at risk
Tonsillitis	Infections and infestations	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected270 at risk
Urinary tract infection	Infections and infestations	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0012 events2 affected270 at risk
Viral infection	Infections and infestations	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected270 at risk
Skull fracture	Injury, poisoning and procedural complications	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected270 at risk
Moraxella test positive	Investigations	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected270 at risk
Dehydration	Metabolism and nutrition disorders	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected270 at risk
Failure to thrive	Metabolism and nutrition disorders	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected270 at risk
Cognitive disorder	Nervous system disorders	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected270 at risk
Convulsion	Nervous system disorders	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected270 at risk
Febrile convulsion	Nervous system disorders	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected270 at risk
Hypotonia	Nervous system disorders	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected270 at risk
Sensory disturbance	Nervous system disorders	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected270 at risk
Vaginal laceration	Reproductive system and breast disorders	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected270 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected255 at risk EG0010 events0 affected270 at risk
Colectomy	Surgical and medical procedures	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected270 at risk
Colostomy	Surgical and medical procedures	Non-systematic Assessment	EG0000 events0 affected255 at risk EG0011 events1 affected270 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Conjunctivitis	Eye disorders	Non-systematic Assessment	EG00058 events58 affected255 at risk EG00152 events52 affected270 at risk
Constipation	Gastrointestinal disorders	Non-systematic Assessment	EG00018 events18 affected255 at risk EG00124 events24 affected270 at risk
Diarrhoea	Gastrointestinal disorders	Non-systematic Assessment	EG00025 events25 affected255 at risk EG00126 events26 affected270 at risk
Teething	Gastrointestinal disorders	Non-systematic Assessment	EG00016 events16 affected255 at risk EG0017 events7 affected270 at risk
Vomiting	Gastrointestinal disorders	Non-systematic Assessment	EG00019 events19 affected255 at risk EG00131 events31 affected270 at risk
Pyrexia	General disorders	Non-systematic Assessment	EG00043 events43 affected255 at risk EG00145 events45 affected270 at risk
Bronchiolitis	Infections and infestations	Non-systematic Assessment	EG00037 events37 affected255 at risk EG00140 events40 affected270 at risk
Bronchitis	Infections and infestations	Non-systematic Assessment	EG00015 events15 affected255 at risk EG00115 events15 affected270 at risk
Candida Nappy Rash	Infections and infestations	Non-systematic Assessment	EG0006 events6 affected255 at risk EG00117 events17 affected270 at risk
Candidiasis	Infections and infestations	Non-systematic Assessment	EG00016 events16 affected255 at risk EG00124 events24 affected270 at risk
Croup Infectious	Infections and infestations	Non-systematic Assessment	EG00015 events15 affected255 at risk EG00121 events21 affected270 at risk
Gastroenteritis	Infections and infestations	Non-systematic Assessment	EG00038 events38 affected255 at risk EG00132 events32 affected270 at risk
Otitis media	Infections and infestations	Non-systematic Assessment	EG000100 events100 affected255 at risk EG001106 events106 affected270 at risk
Otitis media acute	Infections and infestations	Non-systematic Assessment	EG00031 events31 affected255 at risk EG00131 events31 affected270 at risk
Pharyngitis	Infections and infestations	Non-systematic Assessment	EG00024 events24 affected255 at risk EG00132 events32 affected270 at risk
Rhinitis	Infections and infestations	Non-systematic Assessment	EG00019 events19 affected255 at risk EG00120 events20 affected270 at risk
Sinusitis	Infections and infestations	Non-systematic Assessment	EG00010 events10 affected255 at risk EG00115 events15 affected270 at risk
Upper respiratory tract infection	Infections and infestations	Non-systematic Assessment	EG000144 events144 affected255 at risk EG001154 events154 affected270 at risk
Viral infection	Infections and infestations	Non-systematic Assessment	EG00036 events36 affected255 at risk EG00151 events51 affected270 at risk
Bronchial Hyperreactivity	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG00015 events15 affected255 at risk EG0018 events8 affected270 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG00034 events34 affected255 at risk EG00127 events27 affected270 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG00017 events17 affected255 at risk EG00121 events21 affected270 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG00016 events16 affected255 at risk EG0018 events8 affected270 at risk
Dermatitis atopic	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG00017 events17 affected255 at risk EG00117 events17 affected270 at risk
Dermatitis diaper	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG00033 events33 affected255 at risk EG00140 events40 affected270 at risk
Eczema	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG00029 events29 affected255 at risk EG00128 events28 affected270 at risk
Rash	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG00013 events13 affected255 at risk EG00115 events15 affected270 at risk

Group IDs	Group Description	Statistical Method	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment
OG000 OG001	To demonstrate the non-inferiority of seroresponse to diphtheria toxin, when DTaP vaccine is given with MenACWY-CRM compared with when DTaP vaccine is given alone	Miettinen and Nurminen	Group difference	0	2-Sided	95	-2.9	2.6	Yes	Non-Inferiority or Equivalence	The immune seroresponse to diphtheria toxin, when DTaP is given concomitantly with MenACWY-CRM, was considered non-inferior to that of DTaP given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
OG000 OG001	To demonstrate the non-inferiority of seroresponse to tetanus toxin, when DTaP vaccine is given with MenACWY-CRM compared with when DTaP vaccine is given alone	Miettinen and Nurminen	Group difference	0	2-Sided	95	-3.3	3.9	Yes	Non-Inferiority or Equivalence	The immune seroresponse to tetanus toxin, when DTaP is given concomitantly with MenACWY-CRM, was considered non-inferior to that of DTaP given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
OG000 OG001	To demonstrate the non-inferiority of seroresponse to pertussis toxin (PT), when DTaP vaccine is given, compared with MenACWY-CRM compared with when DTaP vaccine is given alone	Miettinen and Nurminen	Group difference	-4	2-Sided	95	-12.1	4.3	Yes	Non-Inferiority or Equivalence	The immune seroresponse to pertussis toxin (PT), when DTaP is given concomitantly with MenACWY-CRM, was considered non-inferior to that of DTaP given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
OG000 OG001	To demonstrate the non-inferiority of seroresponse to pertussis FHA antigen, when DTaP vaccine is given with MenACWY-CRM compared with when DTaP vaccine is given alone	Miettinen and Nurminen	Group difference	4	2-Sided	95	-5.1	13.6	Yes	Non-Inferiority or Equivalence	The immune seroresponse to pertussis (FHA antigen), when DTaP is given concomitantly with MenACWY-CRM, was considered non-inferior to that of DTaP given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
OG000 OG001	To demonstrate the non-inferiority of seroresponse to pertussis pertactin antigen, when DTaP vaccine is given with MenACWY-CRM compared with when DTaP is given alone.	Miettinen and Nurminen	Group difference	0	2-Sided	95	-8.8	9.1	Yes	Non-Inferiority or Equivalence	The immune seroresponse to pertussis pertactin antigen, when DTaP vaccine is given concomitantly with MenACWY-CRM, was considered non-inferior to that of DTaP given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
OG000 OG001	To demonstrate the non-inferiority of seroresponse to pertussis FIM antigen, when DTaP vaccine is given with MenACWY-CRM compared with when DTaP vaccine is given alone	Miettinen and Nurminen	Group difference	-2	2-Sided	95	-10.6	6.8	Yes	Non-Inferiority or Equivalence	The immune seroresponse to pertussis FIM antigen, when DTaP is given concomitantly with MenACWY-CRM, was considered non-inferior to that of DTaP given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
OG000 OG001	To demonstrate the non-inferiority of seroresponse to hepatitis B antigen, when hepatitis B vaccine is given with MenACWY-CRM compared with when hepatitis B vaccine is given alone.	Miettinen and Nurminen	Group difference	0	2-Sided	95	-5.2	4.5	Yes	Non-Inferiority or Equivalence	The immune seroresponse to hepatitis B, when given concomitantly with MenACWY-CRM, was considered non-inferior to that of hepatitis B vaccine given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
OG000 OG001	To demonstrate the non-inferiority of seroresponse to Hib antigen, when Hib vaccine is given with MenACWY-CRM compared with when Hib vaccine is given alone.	Miettinen and Nurminen	Group difference	5	2-Sided	95	0	11.2	Yes	Non-Inferiority or Equivalence	The immune seroresponse to Hib vaccine, when given concomitantly with MenACWY-CRM, was considered non-inferior to that of Hib vaccine given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
OG000 OG001	To demonstrate the non-inferiority of seroresponse to polio antigen (Type 1), when IPV routine is given with MenACWY-CRM, compared with when IPV is given alone	Miettinen and Nurminen	Group difference	1	2-Sided	95	-3.1	5.4	Yes	Non-Inferiority or Equivalence	The immune seroresponse to polio antigen (Type 1), when IPV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of IPV given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -5%.
OG000 OG001	To demonstrate the non-inferiority of seroresponse to polio antigen (Type 2), when IPV routine is given with MenACWY-CRM, compared with when IPV is given alone	Miettinen and Nurminen	Group difference	1	2-Sided	95	-1.4	3	Yes	Non-Inferiority or Equivalence	The immune seroresponse to polio antigen (Type 2), when IPV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of IPV given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -5%.
OG000 OG001	To demonstrate the non-inferiority of seroresponse to polio antigen (Type 3), when IPV routine is given with MenACWY-CRM, compared with when IPV is given alone	Miettinen and Nurminen	Group difference	-1	2-Sided	95	-3.3	1.7	Yes	Non-Inferiority or Equivalence	The immune seroresponse to polio antigen (Type 3), when IPV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of IPV given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -5%.
OG000 OG001	To demonstrate the non-inferiority of seroresponse to pneumococcal PnC 4 antigen, when PCV is given with MenACWY-CRM, compared with when PCV is given alone	Miettinen and Nurminen	Group difference	1	2-Sided	95	-1.9	4.6	Yes	Non-Inferiority or Equivalence	The immune seroresponse to pneumococcal PnC 4 antigen, when PCV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of PCV given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
OG000 OG001	To demonstrate the non-inferiority of seroresponse to pneumococcal PnC 6B antigen, when PCV is given with MenACWY-CRM, compared with when PCV is given alone	Miettinen and Nurminen	Group difference	-4	2-Sided	95	-10.3	3.2	Yes	Non-Inferiority or Equivalence	The immune seroresponse to pneumococcal PnC 6B antigen, when PCV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of PCV given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
OG000 OG001	To demonstrate the non-inferiority of seroresponse to pneumococcal PnC 9V antigen, when PCV is given with MenACWY-CRM, compared with when PCV is given alone	Miettinen and Nurminen	Group difference	-3	2-Sided	95	-8.7	2.3	Yes	Non-Inferiority or Equivalence	The immune seroresponse to pneumococcal PnC 9V antigen, when PCV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of PCV given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
OG000 OG001	To demonstrate the non-inferiority of seroresponse to pneumococcal PnC 14 antigen, when PCV is given with MenACWY-CRM, compared with when PCV is given alone	Miettinen and Nurminen	Group difference	0	2-Sided	95	-2.8	3.0	Yes	Non-Inferiority or Equivalence	The immune seroresponse to pneumococcal PnC 14 antigen, when PCV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of PCV given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
OG000 OG001	To demonstrate the non-inferiority of seroresponse to pneumococcal PnC 18C antigen, when PCV is given with MenACWY-CRM, compared with when PCV is given alone	Miettinen and Nurminen	Group difference	-3	2-Sided	95	-7.3	1.6	Yes	Non-Inferiority or Equivalence	The immune seroresponse to pneumococcal PnC 18C antigen, when PCV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of PCV given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
OG000 OG001	To demonstrate the non-inferiority of seroresponse to pneumococcal PnC 19F antigen, when PCV is given with MenACWY-CRM, compared with when PCV is given alone	Miettinen and Nurminen	Group difference	3	2-Sided	95	1.3	7.1	Yes	Non-Inferiority or Equivalence	The immune seroresponse to pneumococcal PnC 19F antigen, when PCV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of PCV given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.
OG000 OG001	To demonstrate the non-inferiority of seroresponse to pneumococcal PnC 23F antigen, when PCV is given with MenACWY-CRM, compared with when PCV is given alone	Miettinen and Nurminen	Group difference	-5	2-Sided	95	-11.4	0.5	Yes	Non-Inferiority or Equivalence	The immune seroresponse to pneumococcal PnC 23F antigen, when PCV is given concomitantly with MenACWY-CRM, was considered non-inferior to that of PCV given alone, if the lower limit of the two-sided 95% CI for the difference in the percentage of subjects with antibody response was greater than or equal to -10%.

ID	Term
D016870	Neisseriaceae Infections
D016905	Gram-Negative Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses
D007239	Infections

ID	Term
C556088	MenACWY-CRM vaccine
C541234	diphtheria-tetanus-five component acellular pertussis-inactivated poliomyelitis -Haemophilus influenzae type b conjugate vaccine
D013745	Tetanus Toxoid
C512971	pentacel
D017325	Hepatitis B Vaccines
C075654	Engerix-B
D000069443	Heptavalent Pneumococcal Conjugate Vaccine
C538862	13-valent pneumococcal vaccine
D012411	Rubella Vaccine
D022542	Measles-Mumps-Rubella Vaccine

ID	Term
D014121	Toxoids
D014612	Vaccines
D001688	Biological Products
D045424	Complex Mixtures
D014761	Viral Hepatitis Vaccines
D014765	Viral Vaccines
D022242	Pneumococcal Vaccines
D022541	Streptococcal Vaccines
D001428	Bacterial Vaccines
D017778	Vaccines, Combined
D008458	Measles Vaccine
D009108	Mumps Vaccine

ID	Title	Description
BG000	MenACWY-CRM + Routine Vaccines	Infants received 3 doses of MenACWY-CRM at 2, 4 and 6 months as a infant series vaccination and a toddler dose at 12 months. Infants also received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.
BG001	Routine Vaccines	Infants received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	MenACWY-CRM + Routine Vaccines	Infants received 3 doses of MenACWY-CRM at 2, 4 and 6 months as a infant series vaccination and a toddler dose at 12 months. Infants also received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.			21	255	216	255
EG001	Routine Vaccines	Infants received routine vaccines - 3 doses each of DTaP-IPV/Hib, HBV and PCV at 2, 4 and 6 months; and 1 dose each of PCV and MMR at 12 months.			20	270	227	270