A Study to Evaluate Safety and Immune Response of Novarti... | NCT00518180

A Study to Evaluate Safety and Immune Response of Novarti... | NCT00518180 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
MenACWY + Tdap + HPV	Experimental	Subjects received MenACWY concomitantly with Tdap and HPV at study month 0 followed by two injections of HPV at month 2 and 6	Biological: Novartis Meningococcal ACWY Conjugate Vaccine
MenACWY →Tdap → HPV	Experimental	Subjects received MenACWY at study month 0 followed by one injection of Tdap at month 1, followed by three injections of HPV at months 2, 4, and 8	Biological: Novartis Meningococcal ACWY Conjugate Vaccine
Tdap →MenACWY → HPV	Experimental	Subjects received Tdap at month 0 followed by one injection of MenACWY at month 1, followed by three injections of HPV at months 2, 4, and 8	Biological: Tdap Vaccine

Name	Type	Description	Arm Group Labels	Other Names
Novartis Meningococcal ACWY Conjugate Vaccine	Biological	One dose of vaccine administered intramuscularly	MenACWY + Tdap + HPV

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Subjects With Human Serum Bactericidal Assay (hSBA) Seroresponse	Immune responses to MenACWY, as measured by the percentage of hSBA seroresponders, when given: (a) alone; (b) concomitantly with a Tetanus diphtheria acellular pertussis (Tdap) vaccine and a Human Papillomavirus Recombinant (HPV) vaccine; and (c) when given one month after a Tdap vaccine. Seroresponse to MenACWY: For a subject with baseline hSBA titer <1:4, seroresponse is defined as a postvaccination hSBA titer ≥ 1:8; for a subject with baseline hSBA titer ≥ 1:4, seroresponse is defined as a postvaccination hSBA titer of at least 4 times the baseline.	1 month post MenACWY vaccination
Percentage of Subjects With Antidiphtheria and Antitetanus Toxin ≥1.0 IU/mL	To compare the immune response to Tdap given concomitantly with MenACWY and HPV vaccine with the immune response to Tdap when administered alone	1 month post Tdap vaccination
Geometric Mean Concentrations (GMC) of Antipertussis Toxin (Anti-PT), Antifilamentous Hemagglutinin (Anti-FHA), and Antipertactin (Anti-PRN)	To compare the immune response of Tdap given concomitantly with MenACWY and HPV vaccine with the immune response of Tdap when administered alone	1 month post Tdap vaccination

Secondary Outcomes

Measure	Description	Time Frame
Effect of Concomitant and Sequential Vaccination on hSBA Geometric Mean Titers (GMTs) for A, C, W, and Y Serogroups	The immune responses to the MenACWY conjugate vaccine, as measured by the hSBA Geometric Mean Titers (GMTs) when given: (a) alone, (b) concomitantly with the Tdap vaccine and the HPV vaccine, and (c) when given one month after the Tdap vaccine.	1 month post MenACWY vaccination

Contacts/Locations Module

Name	Affiliation	Role
Novartis Vaccines and Diagnostics	Novartis	Study Director

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
20189491	Result	Arguedas A, Soley C, Loaiza C, Rincon G, Guevara S, Perez A, Porras W, Alvarado O, Aguilar L, Abdelnour A, Grunwald U, Bedell L, Anemona A, Dull PM. Safety and immunogenicity of one dose of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, when administered to adolescents concomitantly or sequentially with Tdap and HPV vaccines. Vaccine. 2010 Apr 19;28(18):3171-9. doi: 10.1016/j.vaccine.2010.02.045. Epub 2010 Feb 26.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	MenACWY+Tdap+HPV	The MenACWY vaccine was administered concomitantly with the Tdap vaccine and the HPV vaccine at study month 0 followed by two injections of the HPV vaccine at months 2 and 6.
FG001	MenACWY→Tdap→HPV

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Comment	Reasons
Withdrawal by Subject		FG00029 subjects FG00130 subjects FG00242 subjects
Lost to Follow-up		FG00030 subjects FG00128 subjects FG00234 subjects
Administrative reason		FG0000 subjects FG0012 subjects FG0022 subjects
Protocol Violation		FG0005 subjects FG0017 subjects FG0024 subjects
Unable to classify		FG0000 subjects FG0012 subjects FG0020 subjects
Adverse Event		FG0001 subjects FG0010 subjects FG0020 subjects

Arm/Group Information

ID	Title	Description
BG000	MenACWY+Tdap+HPV	The MenACWY vaccine was administered concomitantly with the Tdap vaccine and the HPV vaccine at study month 0 followed by two injections of the HPV vaccine at months 2 and 6.
BG001	MenACWY→Tdap→HPV	The MenACWY vaccine was administered at study month 0 followed by one injection of the Tdap vaccine at month 1, followed by three injections of the HPV vaccine at months 2, 4, and 8.
BG002	Tdap →MenACWY → HPV	Tdap vaccine was administered at month 0 followed by one injection of MenACWY at month 1, followed by three injections of the HPV vaccine at months 2, 4, and 8.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG000540 BG001541 BG002539 BG0031620

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00013.9± 2.1 BG00113.9± 2.2 BG00213.8± 2.2 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000308 BG001309 BG002

Race/Ethnicity, Customized

Number

participants

Title

Denominators

Categories

Hispanic

Title	Measurements
	BG000539 BG001541 BG002

Type

Title

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 Human Serum Bactericidal Assay (hSBA) Seroresponse

Immune responses to MenACWY, as measured by the percentage of hSBA seroresponders, when given: (a) alone; (b) concomitantly with a Tetanus diphtheria acellular pertussis (Tdap) vaccine and a Human Papillomavirus Recombinant (HPV) vaccine; and (c) when given one month after a Tdap vaccine.

Seroresponse to MenACWY: For a subject with baseline hSBA titer <1:4, seroresponse is defined as a postvaccination hSBA titer ≥ 1:8; for a subject with baseline hSBA titer ≥ 1:4, seroresponse is defined as a postvaccination hSBA titer of at least 4 times the baseline.

The analysis was performed on the per-protocol (PP) population. A total of 182 subjects were excluded from the PP population due to protocol deviations. The most common protocol deviations were blood draw performed outside the protocol-specified window.

Posted

Number

95% Confidence Interval

Percentage of participants

1 month post MenACWY vaccination

ID	Title	Description
OG000	MenACWY+Tdap+HPV	The MenACWY vaccine was administered concomitantly with the Tdap vaccine and the HPV vaccine at study month 0 followed by two injections of the HPV vaccine at months 2 and 6.
OG001	MenACWY→Tdap→HPV	The MenACWY vaccine was administered at study month 0 followed by one injection of the Tdap vaccine at month 1, followed by three injections of the HPV vaccine at months 2, 4, and 8.
OG002	Tdap →MenACWY → HPV	Tdap vaccine was administered at month 0 followed by one injection of MenACWY at month 1, followed by three injections of the HPV vaccine at months 2, 4, and 8.

Units	Counts
Participants	OG000494 OG001487 OG002458

Title

Denominators

Categories

Serogroup A (N=494, 486, 458)

Title	Measurements
	OG00080(76 to 84) OG00182(78 to 85) OG00287(83 to 90)

Serogroup C (N=476, 472, 457)

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 OG001	Immune response to Men A when MenACWY is administered concomitantly with Tdap and HPV, compared with the immune response to MenACWY when administered alone. Method: ANCOVA. Parameter estimate: Vaccine Group Differences.					Vaccine Group differences (%)	-2			2-Sided	95	-6	3				Yes	Non-Inferiority or Equivalence	The immunogenicity of MenACWY given concomitantly with HPV and Tdap was considered non inferior to the immunogenicity of MenACWY administered alone, if, for each serogroup, the lower limit of the two-sided 95% confidence interval (CI) for the difference in percentage of subjects with seroresponse at one month after MenACWY vaccination (PGroup I minus PGroup II) was greater than -10%.

Primary

Percentage of Subjects With Antidiphtheria and Antitetanus Toxin ≥1.0 IU/mL

To compare the immune response to Tdap given concomitantly with MenACWY and HPV vaccine with the immune response to Tdap when administered alone

The analysis was performed on the per-protocol (PP) population. A total of 183 subjects were excluded from the PP population due to protocol deviations. The most common protocol deviations were blood draw performed outside the protocol-specified window.

Posted

Number

95% Confidence Interval

Percentage of subjects

1 month post Tdap vaccination

ID	Title	Description
OG000	MenACWY+Tdap+HPV	The MenACWY vaccine was administered concomitantly with the Tdap vaccine and the HPV vaccine at study month 0 followed by two injections of the HPV vaccine at months 2 and 6.
OG001	MenACWY→Tdap→HPV	The MenACWY vaccine was administered at study month 0 followed by one injection of the Tdap vaccine at month 1, followed by three injections of the HPV vaccine at months 2, 4, and 8.
OG002	Tdap →MenACWY → HPV	Tdap vaccine was administered at month 0 followed by one injection of MenACWY at month 1, followed by three injections of the HPV vaccine at months 2, 4, and 8.

Secondary

Effect of Concomitant and Sequential Vaccination on hSBA Geometric Mean Titers (GMTs) for A, C, W, and Y Serogroups

The immune responses to the MenACWY conjugate vaccine, as measured by the hSBA Geometric Mean Titers (GMTs) when given: (a) alone, (b) concomitantly with the Tdap vaccine and the HPV vaccine, and (c) when given one month after the Tdap vaccine.

The analysis was performed on the per-protocol (PP) population.

Posted

Geometric Mean

95% Confidence Interval

Titers

1 month post MenACWY vaccination

ID	Title	Description
OG000	MenACWY+Tdap+HPV	The MenACWY vaccine was administered concomitantly with the Tdap vaccine and the HPV vaccine at study month 0 followed by two injections of the HPV vaccine at months 2 and 6.
OG001	MenACWY→Tdap→HPV	The MenACWY vaccine was administered at study month 0 followed by one injection of the Tdap vaccine at month 1, followed by three injections of the HPV vaccine at months 2, 4, and 8
OG002	Tdap → MenACWY→HPV	Tdap was administered at study month 0 followed by one injection of the MenACWY vaccine at month 1, followed by three injections of the HPV vaccine at months 2, 4, and 8.

Secondary

Percentage of Subjects With Anti-HPV Seroconversion

To compare the immune response of HPV vaccine given concomitantly with MenACWY and Tdap to the response when HPV vaccine is given alone. (Immune response against HPV virus-like particles (VLPs) for types 6, 11, 16, and 18 was measured at one month after the third HPV vaccination.) Anti-HPV Seroconversion (SC): SC was defined as negative (baseline HPV titer < type-specific cut-off) for anti-HPV and anti-HPV ≥ an HPV type-specific cut-off at one month after the third HPV injection.

The analysis was performed on the per-protocol (PP) population.

Posted

Number

95% Confidence Interval

Percentage of subjects

1 month post third HPV vaccination

ID	Title	Description
OG000	MenACWY+Tdap+HPV	The MenACWY vaccine was administered concomitantly with the Tdap vaccine and the HPV vaccine at study month 0 followed by two injections of the HPV vaccine at months 2 and 6.
OG001	HPV Alone	Three injections of the HPV vaccine were administered at study months 2, 4, and 8. This arm is a recombination of the two arms listed in the Participant Flow.

Units	Counts
Participants

Secondary

Geometric Mean Titers (GMTs) of Anti-HPV by Competitive Luminex Immunoassay

The analysis was performed on the per-protocol (PP) population.

Posted

Geometric Mean

95% Confidence Interval

Titers

1 month post third HPV vaccination

ID	Title	Description
OG000	MenACWY+Tdap+HPV	The MenACWY vaccine was administered concomitantly with the Tdap vaccine and the HPV vaccine at study month 0 followed by two injections of the HPV vaccine at months 2 and 6.
OG001	HPV Alone	The three injections of the HPV vaccine was administered at study months 2, 4, and 8. This arm is a recombination of the two arms listed in the Participant Flow.

Units	Counts
Participants

Secondary

Percentage of Subjects With hSBA ≥ 1:8, hSBA Titer ≥ 1:4, for A, C, W, and Y Serogroups

The immune responses to MenACWY, as measured by the percentage of subjects with hSBA titer ≥ 1:8, hSBA titer ≥ 1:4, when given: (a) alone, (b) concomitantly with Tdap and HPV vaccine; and (c) when given one month after Tdap.

The analysis was performed on the per-protocol (PP) population.

Posted

Number

95% Confidence Interval

Percentage of subjects

1 month post MenACWY vaccination

ID	Title	Description
OG000	MenACWY+Tdap+HPV	The MenACWY vaccine was administered concomitantly with the Tdap vaccine and the HPV vaccine at study month 0 followed by two injections of the HPV vaccine at months 2 and 6.
OG001	MenACWY→Tdap→HPV	The MenACWY vaccine was administered at study month 0 followed by one injection of the Tdap vaccine at month 1, followed by three injections of the HPV vaccine at months 2, 4, and 8.
OG002	Tdap → MenACWY→HPV	Tdap was administered at study month 0 followed by one injection of the MenACWY vaccine at month 1, followed by three injections of the HPV vaccine at months 2, 4, and 8.

Secondary

The Effect of Sequential Vaccination on Immunogenicity for Diphtheria and Tetanus

The immune response to the Tdap vaccine, as measured by the percentage of subjects with antidiphtheria and antitetanus toxin ≥1.0 IU/mL.

The analysis was performed on the per-protocol (PP) population.

Posted

Number

95% Confidence Interval

Percentages of subjects

1 month post Tdap vaccination

ID	Title	Description
OG000	MenACWY+Tdap+HPV	The MenACWY vaccine was administered concomitantly with the Tdap vaccine and the HPV vaccine at study month 0 followed by two injections of the HPV vaccine at months 2 and 6.
OG001	MenACWY→Tdap→HPV	The MenACWY vaccine was administered at study month 0 followed by one injection of the Tdap vaccine at month 1, followed by three injections of the HPV vaccine at months 2, 4, and 8
OG002	Tdap → MenACWY→HPV	Tdap was administered at study month 0 followed by one injection of the MenACWY vaccine at month 1, followed by three injections of the HPV vaccine at months 2, 4, and 8.

Secondary

Geometric Mean Concentrations (GMC) for Diphtheria and Tetanus

To compare the immune response of Tdap, as measured by the antidiphtheria and antitetanus GMCs, when administered one month after the MenACWY vaccine with the immune response of the Tdap vaccine when administered alone.

The analysis was performed on the per-protocol (PP) population.

Posted

Geometric Mean

95% Confidence Interval

IU/mL

1 month post Tdap vaccination

ID	Title	Description
OG000	MenACWY+Tdap+HPV	The MenACWY vaccine was administered concomitantly with the Tdap vaccine and the HPV vaccine at study month 0 followed by two injections of the HPV vaccine at months 2 and 6.
OG001	MenACWY→Tdap→HPV	The MenACWY vaccine was administered at study month 0 followed by one injection of the Tdap vaccine at month 1, followed by three injections of the HPV vaccine at months 2, 4, and 8
OG002	Tdap → MenACWY→HPV	Tdap was administered at study month 0 followed by one injection of the MenACWY vaccine at month 1, followed by three injections of the HPV vaccine at months 2, 4, and 8.

Secondary

Geometric Mean Titers (GMT) of Pertussis Antigens

To compare the immune response to Tdap administered one month after MenACWY with the immune response to Tdap administered alone.

The analysis was performed on the per-protocol (PP) population.

Posted

Geometric Mean

95% Confidence Interval

Titers

1 month post Tdap vaccination

ID	Title	Description
OG000	MenACWY+Tdap+HPV	The MenACWY vaccine was administered concomitantly with the Tdap vaccine and the HPV vaccine at study month 0 followed by two injections of the HPV vaccine at months 2 and 6.
OG001	MenACWY→Tdap→HPV	The MenACWY vaccine was administered at study month 0 followed by one injection of the Tdap vaccine at month 1, followed by three injections of the HPV vaccine at months 2, 4, and 8
OG002	Tdap → MenACWY→HPV	Tdap was administered at study month 0 followed by one injection of the MenACWY vaccine at month 1, followed by three injections of the HPV vaccine at months 2, 4, and 8.

Secondary

Percentages of Subjects With at Least a 4-fold Rise for PT, FHA, and PRN

To compare the immune response of Tdap, defined by the percentage of subjects with a 4-fold rise in antibody titer over baseline against PT, FHA, PRN, when administered one month after the MenACWY with the immune response of Tdap when administered alone.

The analysis was performed on the per-protocol (PP) population.

Posted

Number

95% Confidence Interval

Percentages of subjects

1 month post Tdap vaccination

ID	Title	Description
OG000	MenACWY+Tdap+HPV	The MenACWY vaccine was administered concomitantly with the Tdap vaccine and the HPV vaccine at study month 0 followed by two injections of the HPV vaccine at months 2 and 6.
OG001	MenACWY→Tdap→HPV	The MenACWY vaccine was administered at study month 0 followed by one injection of the Tdap vaccine at month 1, followed by three injections of the HPV vaccine at months 2, 4, and 8
OG002	Tdap → MenACWY→HPV	Tdap was administered at study month 0 followed by one injection of the MenACWY vaccine at month 1, followed by three injections of the HPV vaccine at months 2, 4, and 8.

Primary

Geometric Mean Concentrations (GMC) of Antipertussis Toxin (Anti-PT), Antifilamentous Hemagglutinin (Anti-FHA), and Antipertactin (Anti-PRN)

To compare the immune response of Tdap given concomitantly with MenACWY and HPV vaccine with the immune response of Tdap when administered alone

The analysis was performed on the per-protocol (PP) population.

Posted

Geometric Mean

95% Confidence Interval

IU/mL

1 month post Tdap vaccination

ID	Title	Description
OG000	MenACWY+Tdap+HPV	The MenACWY vaccine was administered concomitantly with the Tdap vaccine and the HPV vaccine at study month 0 followed by two injections of the HPV vaccine at months 2 and 6.
OG001	MenACWY→Tdap→HPV	The MenACWY vaccine was administered at study month 0 followed by one injection of the Tdap vaccine at month 1, followed by three injections of the HPV vaccine at months 2, 4, and 8.
OG002	Tdap →MenACWY → HPV	Tdap vaccine was administered at month 0 followed by one injection of MenACWY at month 1, followed by three injections of the HPV vaccine at months 2, 4, and 8.

Secondary

Number of Subjects With at Least One Reactogenicity Sign After MenACWY and Tdap Vaccination.

Number of subjects with specified local and systemic reactions were assessed when MenACWY was given alone, one month after Tdap, and concomitantly with Tdap and HPV vaccine.

The analysis was performed on the safety set.

Posted

Number

Subjects

Days 1 to 7

ID	Title	Description
OG000	MenACWY+Tdap+HPV	The MenACWY vaccine was administered concomitantly with the Tdap vaccine and the HPV vaccine at study month 0 followed by two injections of the HPV vaccine at months 2 and 6.
OG001	MenACWY→Tdap → HPV	The MenACWY vaccine was administered at study month 0 followed by one injection of the Tdap vaccine at month 1, followed by three injections of the HPV vaccine at months 2, 4, and 8.
OG002	Tdap → MenACWY →HPV	Tdap vaccine was administered at month 0 followed by one injection of MenACWY at month 1, followed by three injections of the HPV vaccine at months 2, 4, and 8.

Secondary

Number of Subjects With at Least One Reactogenicity Sign After Each HPV Vaccination

Number of subjects with specified local and systemic reactions were solicited for 7 days after the HPV vaccination.

The analysis was performed on the safety population.

Posted

Number

Subjects

Days 1 to 7

ID	Title	Description
OG000	MenACWY+Tdap+HPV	The MenACWY vaccine was administered concomitantly with the Tdap vaccine and the HPV vaccine at study month 0 followed by two vaccinations of the HPV vaccine at month 2 and 6.
OG001	MenACWY→Tdap→HPV	The MenACWY vaccine was administered at study month 0 followed by one injection of the Tdap vaccine at month 1, followed by three injections of the HPV at months 2, 4, and 8
OG002	Tdap → MenACWY → HPV	Tdap vaccine was administered at month 0 followed by one injection of MenACWY at month 1, followed by three injections of HPV at months 2, 4, and 8

Units	Counts

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	MenACWY+Tdap+HPV	The MenACWY vaccine was administered concomitantly with the Tdap vaccine and the HPV vaccine at study month 0 followed by two vaccinations of the HPV vaccine at month 2 and 6.	1	540	495	540
EG001	MenACWY→Tdap→HPV	The MenACWY vaccine was administered at study month 0 followed by one injection of the Tdpa vaccine at month 1, followed by three injections of the HPV at months 2,4 and 8.	7	541	489	541
EG002	Tdap → MenACWY → HPV	Tdpa was administered at month 0 followed by one injection of MenACWY at month 1, followed by three injections of HPV at months 2,4 and 8.	3	539	482	539

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
CUSHING'S SYNDROME	Endocrine disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected540 at risk EG0010 events0 affected541 at risk EG0020 events0 affected539 at risk
BEZOAR	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected540 at risk EG0011 events1 affected541 at risk EG0020 events0 affected539 at risk
APPENDICITIS	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected540 at risk EG0012 events2 affected541 at risk EG0020 events0 affected539 at risk
ROAD TRAFFIC ACCIDENT	Injury, poisoning and procedural complications	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected540 at risk EG0010 events0 affected541 at risk EG0021 events1 affected539 at risk
PITUITARY TUMOUR BENIGN	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected540 at risk EG0010 events0 affected541 at risk EG0020 events0 affected539 at risk
ABORTION SPONTANEOUS	Pregnancy, puerperium and perinatal conditions	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected540 at risk EG0011 events1 affected541 at risk EG0021 events1 affected539 at risk
HYDRONEPHROSIS	Renal and urinary disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected540 at risk EG0010 events0 affected541 at risk EG0021 events1 affected539 at risk
HAEMORRHAGIC OVARIAN CYST	Reproductive system and breast disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected540 at risk EG0011 events1 affected541 at risk EG0020 events0 affected539 at risk
TESTICULAR TORSION	Reproductive system and breast disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected540 at risk EG0011 events1 affected541 at risk EG0020 events0 affected539 at risk
BEHCET'S SYNDROME	Vascular disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected540 at risk EG0011 events1 affected541 at risk EG0020 events0 affected539 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
NAUSEA	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG000191 events124 affected540 at risk EG001255 events133 affected541 at risk EG002289 events142 affected539 at risk
CHILLS	General disorders	MedDRA (17.1)	Systematic Assessment	EG000131 events100 affected540 at risk EG001201 events117 affected541 at risk EG002238 events130 affected539 at risk
INJECTION SITE ERYTHEMA HPV	General disorders	MedDRA (17.1)	Systematic Assessment	EG000212 events134 affected540 at risk EG001147 events105 affected541 at risk EG002166 events101 affected539 at risk
INJECTION SITE INDURATION HPV	General disorders	MedDRA (17.1)	Systematic Assessment	EG000179 events119 affected540 at risk EG001116 events81 affected541 at risk EG002134 events85 affected539 at risk
INJECTION SITE PAIN HPV	General disorders	MedDRA (17.1)	Systematic Assessment	EG000778 events387 affected540 at risk EG001666 events320 affected541 at risk EG002648 events313 affected539 at risk
MALAISE	General disorders	MedDRA (17.1)	Systematic Assessment	EG000284 events171 affected540 at risk EG001402 events209 affected541 at risk EG002428 events194 affected539 at risk
PYREXIA	General disorders	MedDRA (17.1)	Systematic Assessment	EG00077 events62 affected540 at risk EG001129 events88 affected541 at risk EG002123 events84 affected539 at risk
ARTHRALGIA	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG000188 events119 affected540 at risk EG001225 events132 affected541 at risk EG002248 events131 affected539 at risk
MYALGIA	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG000276 events178 affected540 at risk EG001339 events187 affected541 at risk EG002440 events200 affected539 at risk
HEADACHE	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG000519 events260 affected540 at risk EG001749 events284 affected541 at risk EG002802 events278 affected539 at risk
RASH	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Systematic Assessment	EG00036 events31 affected540 at risk EG00164 events47 affected541 at risk EG00266 events42 affected539 at risk
INJECTION SITE ERYTHEMA MENVEO	General disorders	MedDRA (17.1)	Systematic Assessment	EG00080 events69 affected540 at risk EG00168 events66 affected541 at risk EG00271 events65 affected539 at risk
INJECTION SITE ERYTHEMA Tdap	General disorders	MedDRA (17.1)	Systematic Assessment	EG00093 events78 affected540 at risk EG00140 events38 affected541 at risk EG00282 events72 affected539 at risk
INJECTION SITE INDURATION MENVEO	General disorders	MedDRA (17.1)	Systematic Assessment	EG00076 events68 affected540 at risk EG00172 events70 affected541 at risk EG00268 events65 affected539 at risk
INJECTION SITE INDURATION Tdap	General disorders	MedDRA (17.1)	Systematic Assessment	EG000101 events90 affected540 at risk EG00167 events64 affected541 at risk EG002125 events110 affected539 at risk
INJECTION SITE PAIN MENVEO	General disorders	MedDRA (17.1)	Systematic Assessment	EG000307 events264 affected540 at risk EG001289 events246 affected541 at risk EG002266 events239 affected539 at risk
INJECTION SITE PAIN Tdap	General disorders	MedDRA (17.1)	Systematic Assessment	EG000407 events368 affected540 at risk EG001343 events310 affected541 at risk EG002427 events383 affected539 at risk

Ancestor Terms

ID	Term
D016920	Meningitis, Bacterial
D020806	Central Nervous System Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses
D007239	Infections
D008589	Meningococcal Infections
D016870	Neisseriaceae Infections
D016905	Gram-Negative Bacterial Infections
D002494	Central Nervous System Infections
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D000090862	Neuroinflammatory Diseases
D015229	Sexually Transmitted Diseases, Viral
D012749	Sexually Transmitted Diseases
D003141	Communicable Diseases
D004266	DNA Virus Infections
D014777	Virus Diseases
D014412	Tumor Virus Infections
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D001885	Bordetella Infections
D012141	Respiratory Tract Infections
D012140	Respiratory Tract Diseases
D003015	Clostridium Infections
D016908	Gram-Positive Bacterial Infections

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 OG002	Non inferiority of the immune response to diphteria antigen, when Tdap is administered concomitantly with MenACWY and HPV, compared with the immune response to Tdap when administered alone. Method: ANCOVA. Parameter estimate: Vaccine Group Differences.					Vaccine Group differences (%)	2			2-Sided	95	1	4				Yes	Non-Inferiority or Equivalence	Non inferiority of the immune response to Tdap when administered concomitantly with MenACWY and HPV, compared with the immune response to Tdap when administered alone, was demonstrated for the diphteria and tetanus antigens if the lower limits of the two-sided 95% CIs around the difference in the percentages of subjects with ELISA anti-D toxin ≥ 1.0 IU/mL [Group I minus Group III] were greater than -10%.
OG000 OG002	Non inferiority of the immune response to tetanus antigen, when Tdap is administered concomitantly with MenACWY and HPV, compared with the immune response to Tdap when administered alone. Method: ANCOVA. Parameter estimate: Vaccine Group Differences.					Vaccine Group differences (%)	0			2-Sided	95	-1	1				Yes	Non-Inferiority or Equivalence	Non inferiority of the immune response to Tdap when administered concomitantly with MenACWY and HPV, compared with the immune response to Tdap when administered alone, was demonstrated for the diphteria and tetanus antigens if the lower limits of the two-sided 95% CIs around the difference in the percentages of subjects with ELISA anti-D toxin ≥ 1.0 IU/mL [Group I minus Group III] were greater than -10%.

Title

Denominators

Categories

Serogroup A (N=494, 486, 458)

Title	Measurements
	OG00062(52 to 74) OG00167(56 to 80) OG00295(79 to 113)

Serogroup C (N=476, 472, 457)

Title	Measurements
	OG00066(56 to 77) OG00170(60 to 83) OG00268(58 to 79)

Serogroup W (N=487, 474, 458)

Title	Measurements
	OG000146(129 to 165) OG001159(140 to 181) OG002104(91 to 119)

Serogroup Y (N=493, 487, 460)

Title	Measurements
	OG00072(62 to 84) OG00181(70 to 95) OG00257(49 to 67)

Title

Denominators

Categories

HPV 6 (N=361, 737)

Title	Measurements
	OG00099(98 to 100) OG001100(99 to 100)

HPV 11 (N=362, 744)

Title	Measurements
	OG000100(99 to 100) OG001100(99 to 100)

HPV 16 (N=360, 744)

Title	Measurements
	OG000100(99 to 100) OG001100(99 to 100)

HPV 18 (N=364, 743)

Title	Measurements
	OG000100(98 to 100) OG00199(99 to 100)

Title

Denominators

Categories

HPV 6 (N=361, 737)

Title	Measurements
	OG0001059(926 to 1212) OG0011461(1327 to 1608)

HPV 11 (N=362, 744)

Title	Measurements
	OG0001264(1134 to 1408) OG0011701(1575 to 1837)

HPV 16 (N=360, 744)

Title	Measurements
	OG0005286(4705 to 5939) OG0016590(6068 to 7158)

HPV 18 (N=364, 743)

Title	Measurements
	OG000908(798 to 1032) OG0011117(1019 to 1224)

Title

Denominators

Categories

Serogroup A hSBA ≥ 1:8 (N=494, 486, 458)

Title	Measurements
	OG00081(78 to 85) OG00182(79 to 86) OG00289(85 to 91)

Serogroup C hSBA ≥ 1:8 (N=476, 472, 457)

Title	Measurements
	OG00092(89 to 94) OG00190(87 to 93) OG00293(90 to 95)

Serogroup W hSBA ≥ 1:8 (N=487, 474, 458)

Title	Measurements
	OG00098(96 to 99) OG00199(98 to 100) OG00295(93 to 97)

Serogroup Y hSBA ≥ 1:8 (N=493, 487, 460)

Title	Measurements
	OG00093(90 to 95) OG00193(90 to 95) OG00292(90 to 95)

Serogroup A hSBA ≥ 1:4 (N=408, 404, 412)

Title	Measurements
	OG00083(79 to 86) OG00183(79 to 86) OG00290(87 to 93)

Serogroup C hSBA ≥ 1:4 (N=456, 447, 430)

Title	Measurements
	OG00092(90 to 94) OG00192(89 to 94) OG00294(92 to 96)

Serogroup W hSBA ≥ 1:4 (N=478, 471, 443)

Title	Measurements
	OG00098(97 to 99) OG00199(98 to 100) OG00297(95 to 98)

Serogroup Y hSBA ≥ 1:4 (N=465, 456, 438)

Title	Measurements
	OG00094(92 to 96) OG00194(91 to 96) OG00295(93 to 97)

Title

Denominators

Categories

Diphtheria (% ≥1.0 IU/mL)

Title	Measurements
	OG000100(99 to 100) OG001100(99 to 100) OG00298(96 to 99)

Tetanus (% ≥1.0 IU/mL)

Title	Measurements
	OG000100(99 to 100) OG001100(99 to 100) OG002100(99 to 100)

Title

Denominators

Categories

Anti-PT (N=479, 451, 477)

Title	Measurements
	OG00051(47 to 55) OG00179(72 to 87) OG00263(58 to 69)

Anti-FHA (N=489, 457, 485)

Title	Measurements
	OG000342(310 to 376) OG0011106(989 to 1238) OG002511(464 to 563)

Anti-PRN (N=492, 458, 487)

Title	Measurements
	OG000819(727 to 923) OG0011563(1390 to 1758) OG0021197(1061 to 1350)

Title

Denominators

Categories

Anti-PT (N=479, 451, 477)

Title	Measurements
	OG00083(79 to 86) OG00189(86 to 92) OG00286(83 to 89)

Anti-FHA (N=489, 457, 485)

Title	Measurements
	OG00067(63 to 71) OG00190(87 to 93) OG00278(74 to 82)

Anti-PRN (N=492, 458, 487)

Title	Measurements
	OG00086(83 to 89) OG00195(92 to 97) OG00289(85 to 91)

Title

Denominators

Categories

Anti-PT (N=479, 451, 477)

Title	Measurements
	OG00051(47 to 55) OG00179(72 to 87) OG00263(58 to 69)

Anti-FHA (N=489, 457, 485)

Title	Measurements
	OG000342(310 to 376) OG0011106(989 to 1238) OG002511(464 to 563)

Anti-PRN (N=492, 458, 487)

Title	Measurements
	OG000819(727 to 923) OG0011563(1390 to 1758) OG0021197(1061 to 1350)

Group IDs	Group Description	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 OG002	Non inferiority of the immune response to Tdap is administered concomitantly with MenACWY and HPV, compared with the immune response to Tdap when administered alone, for PT antigen. Method: ANCOVA. Parameter estimate: Vaccine Group Ratio.	Vaccine Group Ratio	0.8	2-Sided	95	0.72	0.9	Yes	Non-Inferiority or Equivalence	Tdap concomitant with MenACWY a was considered non inferior to Tdap alone if, for PT, FHA and pertactin, the lower limit of the two-sided 95% CI for the ratio of the GMCs (GMC Group I / GMC Group III) at 1 month after vaccination was > 0.67.
OG000 OG002	Non inferiority of the immune response to Tdap when administered concomitantly with MenACWY and HPV, compared with the immune response to Tdap when administered alone, for PRN antigen. Method: ANCOVA. Parameter estimate: Vaccine Group Ratio.	Vaccine Group Ratio	0.68	2-Sided	95	0.58	0.81	Yes	Non-Inferiority or Equivalence	Tdap concomitant with MenACWY a was considered non inferior to Tdap alone if, for PT, FHA and pertactin, the lower limit of the two-sided 95% CI for the ratio of the GMCs (GMC Group I / GMC Group III) at 1 month after vaccination was > 0.67.
OG000 OG002	Non inferiority of the immune response to Tdap when administered concomitantly with MenACWY and HPV, compared with the immune response to Tdap when administered alon, for FHA antigen. Method: ANCOVA. Parameter estimate: Vaccine Group Ratio.	Vaccine Group Ratio	0.67	2-Sided	95	0.58	0.76	Yes	Non-Inferiority or Equivalence	Tdap concomitant with MenACWY a was considered non inferior to Tdap alone if, for PT, FHA and pertactin, the lower limit of the two-sided 95% CI for the ratio of the GMCs (GMC Group I / GMC Group III) at 1 month after vaccination was > 0.67.

Title

Denominators

Categories

Injection site pain MenACWY

Title	Measurements
	OG000263 OG001246 OG002239

Injection site pain Tdap

Title	Measurements
	OG000367 OG001310 OG002383

Injection site erythema MenACWY

Title	Measurements
	OG00068 OG00166 OG00264

Injection site erythema Tdap

Title	Measurements
	OG00078 OG00138 OG00270

Injection site induration MenACWY

Title	Measurements
	OG00068 OG00170 OG00263

Injection site induration Tdap

Title	Measurements
	OG00090 OG00164 OG002110

Chills post-vaccination 1

Title	Measurements
	OG00077 OG00166 OG00270

Chills post-vaccination 2

Title	Measurements
	OG0000 OG00142 OG00245

Nausea post-vaccination 1

Title	Measurements
	OG00088 OG00172 OG00282

Nausea post-vaccination 2

Title	Measurements
	OG0000 OG00142 OG00264

Malaise post-vaccination 1

Title	Measurements
	OG000133 OG001110 OG002115

Malaise post-vaccination 2

Title	Measurements
	OG0000 OG00191 OG00288

Myalgia post-vaccination 1

Title	Measurements
	OG000146 OG001104 OG002142

Myalgia post-vaccination 2

Title	Measurements
	OG0000 OG00181 OG00282

Arthralgia post-vaccination 1

Title	Measurements
	OG00094 OG00162 OG00276

Arthralgia post-vaccination 2

Title	Measurements
	OG0000 OG00152 OG00252

Headache post-vaccination 1

Title	Measurements
	OG000217 OG001194 OG002200

Headache post-vaccination 2

Title	Measurements
	OG0000 OG001125 OG002138

Rash post-vaccination 1

Title	Measurements
	OG00021 OG00117 OG00220

Rash post-vaccination 2

Title	Measurements
	OG0000 OG00115 OG00213

Fever ≥ 38°Celsius post-vaccination 1

Title	Measurements
	OG00027 OG00119 OG00217

Fever ≥ 38°Celsius post-vaccination 2

Title	Measurements
	OG0000 OG00125 OG00230

Analgesic/Antipyretic Med. Used post-vaccination 1

Title	Measurements
	OG000110 OG00183 OG00296

Analgesic/Antipyretic Med. Used post-vaccination 2

Title	Measurements
	OG0000 OG00158 OG00249

Title

Denominators

Categories

Injection site pain postvaccination 1

Title	Measurements
	OG000265 OG001180 OG002204

Injection site erythema postvaccination 1

Title	Measurements
	OG00074 OG00136 OG00242

Injection site induration postvaccination 1

Title	Measurements
	OG00054 OG00127 OG00226

Injection site pain (N=498, 483, 468) postvac 2

Title	Measurements
	OG000208 OG001208 OG002189

Injection site erythema postvaccination 2

Title	Measurements
	OG00062 OG00148 OG00257

Injection site induration postvaccination 2

Title	Measurements
	OG00046 OG00137 OG00250

Injection site pain postvaccination 3

Title	Measurements
	OG000229 OG001227 OG002208

Injection site erythema postvaccination 3

Title	Measurements
	OG00060 OG00156 OG00255

Injection site induration postvaccination 3

Title	Measurements
	OG00060 OG00147 OG00248

Chills postvaccination 1

Title	Measurements
	OG00077 OG00127 OG00230

Nausea postvaccination 1

Title	Measurements
	OG00088 OG00139 OG00232

Malaise postvaccination 1

Title	Measurements
	OG000133 OG00149 OG00255

Myalgia postvaccination 1

Title	Measurements
	OG000146 OG00132 OG00256

Arthralgia postvaccination 1

Title	Measurements
	OG00094 OG00133 OG00228

Headache postvaccination 1

Title	Measurements
	OG000217 OG00193 OG00297

Rash postvaccination 1

Title	Measurements
	OG00021 OG0017 OG0026

Fever (≥ 38°C) postvaccination 1

Title	Measurements
	OG00027 OG00121 OG00223

Stayed home postvaccination 1

Title	Measurements
	OG000110 OG00126 OG00234

Chills postvaccination 2

Title	Measurements
	OG00023 OG00122 OG00226

Nausea postvaccination 2

Title	Measurements
	OG00038 OG00130 OG00229

Malaise postvaccination 2

Title	Measurements
	OG00053 OG00145 OG00234

Myalgia postvaccination 2

Title	Measurements
	OG00042 OG00138 OG00251

Arthralgia postvaccination 2

Title	Measurements
	OG00030 OG00128 OG00221

Headache postvaccination 2

Title	Measurements
	OG00088 OG00178 OG00271

Rash postvaccination 2

Title	Measurements
	OG0004 OG00111 OG0029

Fever (≥ 38°C) postvaccination 2

Title	Measurements
	OG00017 OG00122 OG00222

Chills postvaccination 3

Title	Measurements
	OG00022 OG00124 OG00225

Nausea postvaccination 3

Title	Measurements
	OG00032 OG00135 OG00234

Malaise postvaccination 3

Title	Measurements
	OG00049 OG00150 OG00241

Myalgia postvaccination 3

Title	Measurements
	OG00053 OG00149 OG00237

Arthralgia postvaccination 3

Title	Measurements
	OG00037 OG00126 OG00230

Headache postvaccination 3

Title	Measurements
	OG00079 OG00185 OG00279

Rash postvaccination 3

Title	Measurements
	OG0009 OG0017 OG00210

Fever (≥ 38°C) postvaccination 3

Title	Measurements
	OG00020 OG00116 OG00225

ID	Term
D008585	Meningitis, Meningococcal
D030361	Papillomavirus Infections
D014917	Whooping Cough
D013742	Tetanus
D008581	Meningitis