Assessing the Effectiveness, Immunogenicity and Safety of Meningococcal ABCWY Vaccine Administered to Healthy Adolescents

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02285777
• Collaborator: (none)
• Enrollment: 189
• Locations: 8
• Arms: 2
• Duration (Months): 6.3
• Patients Per Site: 23.6
• Patients Per Site Per Month: 3.7

Study Details

Study Description

Brief Summary

This is extension of the V102_16 study (NCT02140762). V102_16E1 is designed to assess the effectiveness of a 3-dose vaccination series of MenABCWY, administered according to 0, 2, 6 month schedule, against the same panel of endemic US N. meningitidis serogroup B strains, as measured by enc-hSBA assay. The subjects who completed the parent V102_16 study will be invited at the time of their last study visit to participate in this extension study.

Condition or Disease	Intervention/Treatment	Phase
Meningococcal Disease	Biological: Meningococcal ABCWY; Biological: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 189 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Phase 2b, Controlled, Observer-Blind, Multi-Center Study Assessing the Effectiveness, Immunogenicity and Safety of the 3rd Dose of Novartis Meningococcal ABCWY Vaccine Administered to Healthy Adolescents in the U.S.
• Study Start Date: Dec 1, 2014
• Actual Primary Completion Date: Mar 26, 2015
• Actual Study Completion Date: Jun 11, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MenABCWY Group Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Biological: Meningococcal ABCWY; One dose administered intramuscularly in the deltoid area of a non-dominant arm at Month 6 (Visit 1)
Active Comparator: MenACWY Group Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.	Biological: Placebo; One dose of placebo administered intramuscularly in the deltoid area of a non-dominant arm at Month 6 (Visit 1)

Outcome Measures

Primary Outcome Measures

1. Percentages of Subjects Without Bactericidal Activity at 1:4 Dilution Against Each US Neisseria Meningitides (N. Meningitidis) Serogroup B Strain at 1 Month After the 3-dose Vaccination Series. [At Month 7 (1 month after the 3-dose vaccination series)]

   The effectiveness of three doses of MenABCWY vaccine when compared to one dose of MenACWY vaccine against a panel of US N. meningitidis serogroup B invasive disease strains at 1 month after the 3-dose vaccination series was evaluated in terms of: the combined percentage of subjects without bactericidal activity at 1:4 dilution using the human Serum Bactericidal Assay (hSBA) against each strain in MenABCWY group and MenACWY group. The data provided is an average of the percentage of subjects without bactericidal activity at 1:4 dilution across all 110 strains.

Secondary Outcome Measures

1. Percentages of Subjects Without Bactericidal Activity at 1:4 Dilution Against Each US N. Meningitidis Serogroup B Strain at 4 Months After the 3-dose Vaccination Series. [At Month 10 (4 months after the 3-dose vaccination series)]

   The effectiveness of three doses of MenABCWY vaccine when compared to one dose of MenACWY vaccine against a panel of US N. meningitidis serogroup B invasive disease strains at 4 months after the 3-dose vaccination series was evaluated in terms of: the combined percentage of subjects without bactericidal activity at 1:4 dilution using the hSBA against each strain in MenABCWY Group and MenACWY Group. The data provided is an average of the percentage of subjects without bactericidal activity at 1:4 dilution across all 110 strains.

2. Percentages of Subjects Without Bactericidal Activity at 1:8 Dilution Against Each US N. Meningitidis Serogroup B Strain at 1 and 4 Months After the 3-dose Vaccination Series. [At Months 7 and 10 (1 and 4 months after the 3-dose vaccination series)]

   The effectiveness of three doses of MenABCWY vaccine when compared to one dose of MenACWY vaccine against a panel of US N. meningitidis serogroup B invasive disease strains at 1 and 4 months after the 3-dose vaccination series were evaluated in terms of: the combined percentage of subjects without bactericidal activity at 1:8 dilution using the hSBA against each strain in MenABCWY Group and MenACWY Group. The data provided is an average of the percentage of subjects without bactericidal activity at 1:8 dilution across all 110 strains.

3. Percentages of US N. Meningitidis Serogroup B Strains Killed at 1:4 and 1:8 Dilutions at 1 and 4 Months After the 3-dose Vaccination Series [At Month 6 (before the 3-dose vaccination series) and at Months 7 and 10 (1 and 4 months after the 3-dose vaccination series)]

   The mean percentage of US N. meningitidis serogroup B strains killed by each subject, at 1:4 and 1:8 dilutions before the 3-dose vaccination series, at Month 6 (PRE) and at 1 and 4 months after the 3-dose vaccination series (Month 7 and Month 10).

4. Percentages of Subjects With Enc-hSBA ≥ 1:4 and Enc-hSBA ≥1:8 at 1 and 4 Months After the 3-dose Vaccination Series [At Months 7 and 10 (1 and 4 months after the 3-dose vaccination series)]

   The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY vaccine, in terms of percentages of subjects with enc-hSBA ≥ 1:4 and enc-hSBA ≥ 1:8 against four N. meningitidis serogroup B test strains (M14459, M07-0241084, 96217 and NZ98/254) at 1 and 4 months after the 3-dose vaccination series (Month 7 and Month 10).

5. HT-hSBA Geometric Mean Titers (GMTs) Against the N. Meningitidis Serogroup B Test Strains [At Months 7 and 10 (1 and 4 months after the 3-dose vaccination series)]

   The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY vaccine, in terms of HT-hSBA GMTs against four N. meningitidis serogroup B test strains (M14459, M07-0241084, 96217 and NZ98/254) after the 3-dose vaccination series.

6. Percentages of Subjects With HT-hSBA Titers Against N. Meningitidis Serogroup B Test Strains ≥ Lower Limit of Quantitation (LLQ) at 1 Month After the 3-dose Vaccination Series. [At Month 7 (1 month after the 3-dose vaccination series)]

   The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of percentages of subjects with HT-hSBA titers ≥ LLQ against serogroup N. meningitidis B test strains (M14459, M07-0241084, 96217 and NZ98/254), at 1 month after the 3-dose vaccination series.The LLQ cut off values for strains 96217, M07-0241084,M14459 and NZ98/254 were 8.6, 8.9, 8 and 8.2 respectively.

7. Percentages of Subjects With HT-hSBA Titers Against N. Meningitidis Serogroup B Test Strains ≥ LLQ at 4 Months After the 3-dose Vaccination Series [At Month 10 (4 months after the 3-dose vaccination series)]

   The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of percentages of subjects with HT-hSBA titers ≥ LLQ against serogroup N. meningitidis B test strains (M14459, M07-0241084, 96217 and NZ98/254), at 4 months after the 3-dose vaccination series. The LLQ cut off values for the strains 96217, M07-0241084,M14459 and NZ98/254 were 8.6,8.9, 8 and 8.2 respectively.

8. Percentages of Subjects With a Two-fold Rise in HT-hSBA Titers Against the N. Meningitidis Serogroup B Test Strains at 1 and 4 Months After the 3-dose Vaccination Series. [At Months 7 and 10 (1 and 4 months after the 3-dose vaccination series)]

   The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with a two-fold rise in HT-hSBA titers against the N. meningitidis serogroup B test strains, at 1 and 4 months after the 3-dose vaccination series. The two-fold titers rise is defined as: a) for subjects with pre-vaccination (month 6 from the parent study) HT-hSBA titers < LLQ, postvaccination HT-hSBA titers ≥ 2 LLQ; b) for subjects with pre-vaccination (month 6 from the parent study) HT-hSBA titers ≥ LLQ, an increase of at least two times the pre-vaccination HT-hSBA titers.

9. Percentages of Subjects With a Three-fold Rise in HT-hSBA Titers Against the N. Meningitidis Serogroup B Test Strains at 1 and 4 Months After the 3-dose Vaccination Series. [At months 7 and 10 (1 and 4 months after 3-dose vaccination series)]

   The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with a three-fold rise in HT-hSBA titers against the N. meningitidis serogroup B test strains, at 1 and 4 months after the 3-dose vaccination series. The three-fold titers rise is defined as: a) for subjects with pre-vaccination (Month 6 from the parent study) HT-hSBA titers < LLQ, postvaccination HT-hSBA titers ≥ 3 LLQ; b) for subjects with pre-vaccination (Month 6 from the parent study) HT-hSBA titers ≥ LLQ, an increase of at least three times the pre-vaccination HT-hSBA titers.

10. Percentages of Subjects With a Four-fold Rise in HT-hSBA Titers Against the N. Meningitidis Serogroup B Test Strains at 1 and 4 Months After the 3-dose Vaccination Series. [At Months 7 and 10 (1 and 4 months after the 3-dose vaccination series)]

    The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with a four-fold rise in HT-hSBA titers against the N. meningitidis serogroup B test strains, at 1 and 4 months after the 3-dose vaccination series. The four-fold titers rise is defined as: a) for subjects with pre-vaccination (Month 6 from the parent study) HT-hSBA titers < LLQ, postvaccination HT-hSBA titers ≥ 4 LLQ; b) for subjects with pre-vaccination (Month 6 from the parent study) HT-hSBA titers ≥ LLQ, an increase of at least four times the pre-vaccination HT-hSBA titers.

11. HT-hSBA GMTs Against N. Meningitidis Serogroups A, C, W and Y. [At Months 7 and 10 (1 and 4 months after the 3-dose vaccination series)]

    The immunogenicity of three doses of MenABCWY compared to a single dose of MenACWY vaccine, in terms of HT-hSBA GMTs to serogroups A, C, W, and Y, at 1 and 4 months after the 3-dose vaccination series.

12. Percentages of Subjects With HT-hSBA Titers Against the N. Meningitidis Serogroup A, C, W and Y ≥ LLQ at 1 Month After the 3- Dose Vaccination Series [At Month 7 (1 month after the 3-dose vaccination series)]

    The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with HT-hSBA titers ≥ LLQ against serogroups A, C, W, Y, at 1 month after the 3-dose vaccination series.The LLQ cut off values for serogroups A,C,W and Y were 22.7,5.2, 39.6 and 14.7 respectively.

13. Percentages of Subjects With HT-hSBA Titers Against the N. Meningitidis Serogroup A, C, W and Y ≥ LLQ at 4 Months After the 3-dose Vaccination Series [At Month 10 (4 months after the 3-dose vaccination series)]

    The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with HT-hSBA titers ≥ LLQ against serogroups A, C, W, Y, at 4 months after the 3-dose vaccination series. The LLQ cut off values for serogroups A, C, W and Y were 22.7,5.2,39.6 and 14.7 respectively.

14. Percentage of Subjects With Two-fold Rise in HT-hSBA Titers Against the N. Meningitidis Serogroups A, C,W and Y at 1 and 4 Months After the 3-dose Vaccination Series. [At Months 7 and 10 (1 and 4 months after the 3-dose vaccination series)]

    The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with a two-fold rise in HT-hSBA titers against the N. meningitidis serogroups A, C, W and Y at 1 and 4 months after the 3-dose vaccination series. The two-fold titers rise is defined as: a) for subjects with pre-vaccination (Month 6 from the parent study) HT-hSBA titers < LLQ, postvaccination HT-hSBA titers ≥ 2 LLQ; b) for subjects with pre-vaccination (Month 6 from the parent study) HT-hSBA titers ≥ LLQ, an increase of at least two times the pre-vaccination HT-hSBA titers.

15. Percentage of Subjects With Three-fold Rise in HT-hSBA Titers Against the N. Meningitidis Serogroups A, C, W and Y at 1 and 4 Months After the 3-dose Vaccination Series. [At Months 7 and 10 (1 and 4 months after the 3-dose vaccination series)]

    The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with a three-fold rise in HT-hSBA titers against the N. meningitidis serogroups A, C, W and Y, at 1 and 4 months after the 3-dose vaccination series. The three-fold titers rise is defined as: a) for subjects with pre-vaccination (Month 6 from the parent study) HT-hSBA titers < LLQ, postvaccination HT-hSBA titers ≥ 3 LLQ; b) for subjects with pre-vaccination (Month 6 from the parent study) HT-hSBA titers ≥ LLQ, an increase of at least three times the pre-vaccination HT-hSBA titers.

16. Percentage of Subjects With Four-fold Rise in HT-hSBA Titers Against the N. Meningitidis Serogroups A, C, W and Y at 1 and 4 Months After the 3-dose Vaccination Series. [At Months 7 and 10 (1 and 4 months after the 3-dose vaccination series)]

    The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with a four-fold rise in HT-hSBA titers against the N. meningitidis serogroups A, C, W and Y, at 1 and 4 months after the 3-dose vaccination series. The four-fold titers rise is defined as: a) for subjects with pre-vaccination (Month 6 from the parent study) HT-hSBA titers < LLQ, postvaccination HT-hSBA titers ≥ 4 LLQ; b) for subjects with pre-vaccination (Month 6 from the parent study) HT-hSBA titers ≥ LLQ, an increase of at least four times the pre-vaccination HT-hSBA titers.

17. Percentages of Subjects With HT-hSBA Titers Against N. Meningitidis Serogroup B Test Strains≥ 5, ≥ 8, ≥ 16, ≥ 32, ≥ 64, ≥ 128 at 1 Month After the 3-dose Vaccination Series [At Month 7 (1 month after the 3-dose vaccination series)]

    The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of percentages of subjects with HT-hSBA titers ≥ 5, ≥ 8, ≥ 16, ≥ 32, ≥ 64, ≥ 128 against serogroup N. meningitidis B test strains (M14459, M07-0241084, 96217 and NZ98/254), at 1 month after the 3-dose vaccination series.

18. Percentages of Subjects With HT-hSBA Titers Against N. Meningitidis Serogroup B Test Strains ≥ 5, ≥ 8, ≥ 16, ≥ 32, ≥ 64, ≥ 128 at 4 Months After the 3-dose Vaccination Series [At Month 10 (4 months after the 3-dose vaccination series)]

    The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of percentages of subjects with HT-hSBA titers ≥ 5, ≥ 8, ≥ 16, ≥ 32, ≥ 64, ≥ 128 against serogroup N. meningitidis B test strains (M14459, M07-0241084, 96217 and NZ98/254), at 4 months after the 3-dose vaccination series.

19. Percentages of Subjects With HT-hSBA Titers Against the N. Meningitidis Serogroup A, C, W and Y ≥ 8, ≥ 16, ≥ 32, ≥ 64, ≥128 at 1 Month After the 3- Dose Vaccination Series [At Month 7 (1 month after the 3-dose vaccination series)]

    The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with HT-hSBA titers ≥ 8, ≥ 16, ≥ 32, ≥ 64, ≥128 against serogroups A, C, W, Y, at 1 month after the 3-dose vaccination series.

20. Percentages of Subjects With HT-hSBA Titers Against the N. Meningitidis Serogroup A, C, W and Y ≥8, ≥ 16, ≥ 32, ≥ 64, ≥128 at 4 Months After the 3-dose Vaccination Series [At Month 10 (4 months after the 3-dose vaccination series)]

    The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with HT-hSBA titers≥ 8, ≥ 16, ≥ 32, ≥ 64, ≥ 128 against serogroups A, C, W, Y, at 4 months after the 3-dose vaccination series.

21. Number of Subjects Reporting Any Solicited Local or Systemic Adverse Events (AEs) [Day 1 (6 hours) to Day 7 after vaccination]

    Number of subjects reporting any solicited local or systemic AEs from Day 1 (6 hours) to Day 7 after any meningococcal vaccination is reported. Assessed solicited local symptoms were induration, erythema and pain. Assessed solicited general symptoms were fatigue, myalgia, arthralgia, headache, fever, chills and loss of appetite. Other solicited data included prevention of pain/fever and treatment of pain/fever. Any = occurrence of the symptom regardless of intensity grade.

22. Number of Subjects Reporting Any Unsolicited AEs [Day 1 to Day 30 after any vaccination]

    The number of subjects reporting unsolicited AEs after any vaccination is reported. An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

23. Number of Subjects Reporting Any Serious Adverse Events (SAEs), Medically-attended AEs and AEs Leading to Premature Withdrawal. [During the entire study period (from Day 0 up to Month 10)]

    The number of subjects reporting any SAEs, medically-attended AEs and AEs leading to premature withdrawal during the entire study period is reported. SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. MAEs were defined as events for which the subject received medical attention defined as hospitalization, an emergency room visit, or a visit to or from medical personnel (medical doctor) for any reason. Any was defined as the occurrence of any unsolicited AE regardless of intensitygrade or relation to vaccination.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 19 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adolescents who completed V102_16 study and received the study vaccines as assigned in the protocol (either two doses of the MenABCWY or one dose each of MenACWY and Placebo).

Exclusion Criteria:

• Serious, acute, or chronic illnesses. Previous or suspected disease caused by N. meningitidis.

• History of any meningococcal vaccine administration other than vaccination given in the parent V102_16 protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Huntsville	Alabama	United States	35802
2	GSK Investigational Site	Jonesboro	Arkansas	United States	72401
3	GSK Investigational Site	Melbourne	Florida	United States	32934
4	GSK Investigational Site	Newton	Kansas	United States	67114
5	GSK Investigational Site	Wichita	Kansas	United States	67207
6	GSK Investigational Site	Louisville	Kentucky	United States	40207
7	GSK Investigational Site	Omaha	Nebraska	United States	68134
8	GSK Investigational Site	Cleveland	Ohio	United States	44121

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02285777
• Other Study ID Numbers: 205232; V102_16E1
• First Posted: Nov 7, 2014
• Last Update Posted: Sep 24, 2018
• Last Verified: May 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Meningococcal Infections

Study Results

Participant Flow

Recruitment Details	189 subjects were enrolled from 1 center in United States
Pre-assignment Detail	An Interactive Response Technology (IRT) was used in the study. At Month 6 Visit of the parent study, IRT allocated the study vaccines (either MenABCWY or placebo) to the subject. Subject received either a 3rd dose of MenABCWY or one dose of a placebo, depending on their assigned vaccine group in parent study.

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Period Title: Overall Study
STARTED	95	94
COMPLETED	90	91
NOT COMPLETED	5	3

Baseline Characteristics

Arm/Group Title	MenABCWY Group	MenACWY Group	Total
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.	Total of all reporting groups
Overall Participants	95	94	189
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	12.8 (2.36)	12.4 (2.4)	12.6 (2.38)
Sex: Female, Male (Count of Participants)
Female	40 42.1%	33 35.1%	73 38.6%
Male	55 57.9%	61 64.9%	116 61.4%
Race/Ethnicity, Customized (Count of Participants)
AMERICAN INDIAN OR ALASKA NATIVE	0 0%	2 2.1%	2 1.1%
ASIAN	1 1.1%	0 0%	1 0.5%
BLACK OR AFRICAN AMERICAN	16 16.8%	21 22.3%	37 19.6%
NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER	0 0%	0 0%	0 0%
WHITE	74 77.9%	66 70.2%	140 74.1%
OTHER	4 4.2%	5 5.3%	9 4.8%

Outcome Measures

1. Primary Outcome

Title	Percentages of Subjects Without Bactericidal Activity at 1:4 Dilution Against Each US Neisseria Meningitides (N. Meningitidis) Serogroup B Strain at 1 Month After the 3-dose Vaccination Series.
Description	The effectiveness of three doses of MenABCWY vaccine when compared to one dose of MenACWY vaccine against a panel of US N. meningitidis serogroup B invasive disease strains at 1 month after the 3-dose vaccination series was evaluated in terms of: the combined percentage of subjects without bactericidal activity at 1:4 dilution using the human Serum Bactericidal Assay (hSBA) against each strain in MenABCWY group and MenACWY group. The data provided is an average of the percentage of subjects without bactericidal activity at 1:4 dilution across all 110 strains.
Time Frame	At Month 7 (1 month after the 3-dose vaccination series)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS-Effectiveness (Month 7)- included all screened subjects who provided informed consent & demographic &/or baseline screening assessments, received a subject ID & vaccination,& who provided evaluable serum sample with enc-hSBA result for at least 1 endemic N. meningitidis serogroup B invasive disease strain at Month 7.

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	93	93
Number [Percentages of subjects]	21.1	73.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, MenACWY Group
	Comments	The Vaccine Effectiveness (VE) at 1 month after the 3-dose vaccination series for each strain is defined as [1 - (percentage of subjects without bactericidal activity at 1:4 dilution in MenABCWY group/percentage of subjects without bactericidal activity at 1:4 dilution in MenACWY group)] x 100.The combined VE across all strains was computed by mean of a generalized linear model.
	Type of Statistical Test	Other
	Comments	Pre-specified.
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Generalized Linear Model
	Comments	To obtain the VE measure which is a measure based on RR, BINOMIAL DISTRIBUTION & LOG LINK options were used to compute log10 RR & corresponding CI.
Method of Estimation	Estimation Parameter	Vaccine Effectiveness
	Estimated Value	71
	Confidence Interval	(2-Sided) 95%; 69 to 73
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentages of Subjects Without Bactericidal Activity at 1:4 Dilution Against Each US N. Meningitidis Serogroup B Strain at 4 Months After the 3-dose Vaccination Series.
Description	The effectiveness of three doses of MenABCWY vaccine when compared to one dose of MenACWY vaccine against a panel of US N. meningitidis serogroup B invasive disease strains at 4 months after the 3-dose vaccination series was evaluated in terms of: the combined percentage of subjects without bactericidal activity at 1:4 dilution using the hSBA against each strain in MenABCWY Group and MenACWY Group. The data provided is an average of the percentage of subjects without bactericidal activity at 1:4 dilution across all 110 strains.
Time Frame	At Month 10 (4 months after the 3-dose vaccination series)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS-Effectiveness (Month 10)- included all screened subjects who provided informed consent & demographic &/or baseline screening assessments, received a subject ID & vaccination, & provided evaluable serum sample with the enc-hSBA result for at least 1 endemic N. meningitidis serogroup B invasive disease strain at Month 10

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	90	90
Number [Percentages of subjects]	33.9	69.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, MenACWY Group
	Comments	The Vaccine Effectiveness (VE) at 4 months after the 3-dose vaccination series for each strain is defined as [1 - (percentage of subjects without bactericidal activity at 1:4 dilution in MenABCWY group/percentage of subjects without bactericidal activity at 1:4 dilution in MenACWY group)] x 100. The combined VE across all strains was computed by mean of a generalized linear model.
	Type of Statistical Test	Other
	Comments	Pre-specified.
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Generalized Linear Model
	Comments	To obtain the VE measure which is a measure based on RR, BINOMIAL DISTRIBUTION & LOG LINK options were used to compute log10 RR & corresponding CI.
Method of Estimation	Estimation Parameter	Vaccine Effectiveness
	Estimated Value	51
	Confidence Interval	(2-Sided) 95%; 48 to 55
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentages of Subjects Without Bactericidal Activity at 1:8 Dilution Against Each US N. Meningitidis Serogroup B Strain at 1 and 4 Months After the 3-dose Vaccination Series.
Description	The effectiveness of three doses of MenABCWY vaccine when compared to one dose of MenACWY vaccine against a panel of US N. meningitidis serogroup B invasive disease strains at 1 and 4 months after the 3-dose vaccination series were evaluated in terms of: the combined percentage of subjects without bactericidal activity at 1:8 dilution using the hSBA against each strain in MenABCWY Group and MenACWY Group. The data provided is an average of the percentage of subjects without bactericidal activity at 1:8 dilution across all 110 strains.
Time Frame	At Months 7 and 10 (1 and 4 months after the 3-dose vaccination series)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS-Effectiveness (Months 7 & 10)- included all screened subjects who provided consent & demographic &/or baseline screening assessments, received subject ID & vaccination, & provided evaluable serum sample with the enc-hSBA result for at least 1 endemic N. meningitidis serogroup B invasive disease strain at Months 7 & 10.

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	93	93
Combined Serogroup B Strains (Month 7)	36.9	75.8
Combined Serogroup B Strains (Month 10)	60.3	79.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, MenACWY Group
	Comments	The Vaccine Effectiveness (VE) at 1 month after the 3-dose vaccination series for each strain is defined as [1 - (percentage of subjects without bactericidal activity at 1:8 dilution in MenABCWY group/percentage of subjects without bactericidal activity at 1:8 dilution in MenACWY group)] x 100. The combined VE across all strains was computed by mean of a generalized linear model.
	Type of Statistical Test	Other
	Comments	Pre-specified.
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Generalized Linear Model
	Comments	To obtain the VE measure which is a measure based on RR, BINOMIAL DISTRIBUTION & LOG LINK options were used to compute log10 RR & corresponding CI.
Method of Estimation	Estimation Parameter	Vaccine Effectiveness
	Estimated Value	51
	Confidence Interval	(2-Sided) 95%; 48 to 54
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MenABCWY Group, MenACWY Group
	Comments	The Vaccine Effectiveness (VE) at 4 months after the 3-dose vaccination series for each strain is defined as [1 - (percentage of subjects without bactericidal activity at 1:8 dilution in MenABCWY group/percentage of subjects without bactericidal activity at 1:8 dilution in MenACWY group)] x 100. The combined VE across all strains was computed by mean of a generalized linear model.
	Type of Statistical Test	Other
	Comments	Pre-specified.
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Generalized Linear Model
	Comments	To obtain the VE measure which is a measure based on RR, BINOMIAL DISTRIBUTION & LOG LINK options were used to compute log10 RR & corresponding CI.
Method of Estimation	Estimation Parameter	Vaccine Effectiveness
	Estimated Value	24
	Confidence Interval	() 95%; 20 to 28
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentages of US N. Meningitidis Serogroup B Strains Killed at 1:4 and 1:8 Dilutions at 1 and 4 Months After the 3-dose Vaccination Series
Description	The mean percentage of US N. meningitidis serogroup B strains killed by each subject, at 1:4 and 1:8 dilutions before the 3-dose vaccination series, at Month 6 (PRE) and at 1 and 4 months after the 3-dose vaccination series (Month 7 and Month 10).
Time Frame	At Month 6 (before the 3-dose vaccination series) and at Months 7 and 10 (1 and 4 months after the 3-dose vaccination series)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS-Effectiveness (Months 6, 7 & 10)- included all screened subjects who provided consent & demographic &/or baseline screening assessments, got subject ID & vaccination, & provided serum sample with enc-hSBA result for at least 1 endemic N. meningitidis serogroup B invasive disease strain before Month 6 & at Months 7 & 10

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	93	93
1:4, PRE	56.97 (18.134)	22.94 (17.764)
1:4, Month 7	77.78 (10.041)	21.91 (16.885)
1:4, Month 10	62.37 (15.976)	22.49 (17.094)
1:8, PRE	28.81 (17.086)	11.53 (11.705)
1:8, Month 7	56.95 (14.389)	11.4 (11.266)
1:8, Month 10	31.46 (19.434)	11.15 (10.774)

5. Secondary Outcome

Title	Percentages of Subjects With Enc-hSBA ≥ 1:4 and Enc-hSBA ≥1:8 at 1 and 4 Months After the 3-dose Vaccination Series
Description	The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY vaccine, in terms of percentages of subjects with enc-hSBA ≥ 1:4 and enc-hSBA ≥ 1:8 against four N. meningitidis serogroup B test strains (M14459, M07-0241084, 96217 and NZ98/254) at 1 and 4 months after the 3-dose vaccination series (Month 7 and Month 10).
Time Frame	At Months 7 and 10 (1 and 4 months after the 3-dose vaccination series)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS-Immunogenicity (Months 7 &10)- included all screened subjects who provided consent & demographic &/or baseline screening assessments, received a subject ID & vaccination, & provided evaluable serum samples at Months 7 & 10 & whose immunogenicity assay result was available for at least one serogroup B test strain.

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	92	91
M14459 (≥ 1:4, Month 7)	98	12
M14459 (≥ 1:4, Month 10)	72	12
M14459 (≥ 1:8, Month 7)	67	2
M14459 (≥ 1:8, Month 10)	21	1
M07-0241084 (≥ 1:4, Month 7)	81	21
M07-0241084 (≥ 1:4, Month 10)	46	22
M07-0241084 (≥ 1:8, Month 7)	38	5
M07-0241084 (≥ 1:8, Month 10)	11	6
96217 (≥ 1:4, Month 7)	99	48
96217 (≥ 1:4, Month 10)	100	41
96217 (≥ 1:8, Month 7)	99	17
96217 (≥ 1:8, Month 10)	99	16
NZ98/254 (≥ 1:4, Month 7)	76	1
NZ98/254 (≥ 1:4, Month 10)	34	1
NZ98/254 (≥ 1:8, Month 7)	39	1
NZ98/254 (≥ 1:8, Month 10)	4	0

6. Secondary Outcome

Title	HT-hSBA Geometric Mean Titers (GMTs) Against the N. Meningitidis Serogroup B Test Strains
Description	The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY vaccine, in terms of HT-hSBA GMTs against four N. meningitidis serogroup B test strains (M14459, M07-0241084, 96217 and NZ98/254) after the 3-dose vaccination series.
Time Frame	At Months 7 and 10 (1 and 4 months after the 3-dose vaccination series)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS-Immunogenicity (Months 7 &10)- included all screened subjects who provided consent & demographic &/or baseline screening assessments, received a subject ID & vaccination, & provided evaluable serum samples at Months 7 & 10 & whose immunogenicity assay result was available for at least one serogroup B test strain.

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	91	91
M14459, Month 7	23.12	1.1
M14459, Month 10	3.93	1.18
M07-0241084, Month 7	12.26	1.74
M07-0241084, Month 10	3.04	1.68
96217, Month 7	367.29	4.02
96217, Month 10	142.06	3.32
NZ98/254, Month 7	19.69	1.02
NZ98/254, Month 10	3.75	1.04

7. Secondary Outcome

Title	Percentages of Subjects With HT-hSBA Titers Against N. Meningitidis Serogroup B Test Strains ≥ Lower Limit of Quantitation (LLQ) at 1 Month After the 3-dose Vaccination Series.
Description	The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of percentages of subjects with HT-hSBA titers ≥ LLQ against serogroup N. meningitidis B test strains (M14459, M07-0241084, 96217 and NZ98/254), at 1 month after the 3-dose vaccination series.The LLQ cut off values for strains 96217, M07-0241084,M14459 and NZ98/254 were 8.6, 8.9, 8 and 8.2 respectively.
Time Frame	At Month 7 (1 month after the 3-dose vaccination series)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS-Immunogenicity (Month 7)- included all screened subjects who provided consent & demographic &/or baseline screening assessments, received a subject ID & vaccination, & provided evaluable serum samples at Month 7 & whose immunogenicity assay result was available for at least one serogroup B test strain.

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	91	90
M07-0241084, Month 7	63	12
M14459, Month 7	90	1
NZ98/254, Month 7	79	1
96217, Month 7	100	37

8. Secondary Outcome

Title	Percentages of Subjects With HT-hSBA Titers Against N. Meningitidis Serogroup B Test Strains ≥ LLQ at 4 Months After the 3-dose Vaccination Series
Description	The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of percentages of subjects with HT-hSBA titers ≥ LLQ against serogroup N. meningitidis B test strains (M14459, M07-0241084, 96217 and NZ98/254), at 4 months after the 3-dose vaccination series. The LLQ cut off values for the strains 96217, M07-0241084,M14459 and NZ98/254 were 8.6,8.9, 8 and 8.2 respectively.
Time Frame	At Month 10 (4 months after the 3-dose vaccination series)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS-Immunogenicity (Month 10)- included all screened subjects who provided informed consent & demographic &/or baseline screening assessments, received a subject ID & vaccination, & provided evaluable serum samples at Month 10 and whose immunogenicity assay result was available for at least one serogroup strain.

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	88	91
96217	99	32
M07-0241084	23	12
M14459	36	3
NZ98/254	33	1

9. Secondary Outcome

Title	Percentages of Subjects With a Two-fold Rise in HT-hSBA Titers Against the N. Meningitidis Serogroup B Test Strains at 1 and 4 Months After the 3-dose Vaccination Series.
Description	The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with a two-fold rise in HT-hSBA titers against the N. meningitidis serogroup B test strains, at 1 and 4 months after the 3-dose vaccination series. The two-fold titers rise is defined as: a) for subjects with pre-vaccination (month 6 from the parent study) HT-hSBA titers < LLQ, postvaccination HT-hSBA titers ≥ 2 LLQ; b) for subjects with pre-vaccination (month 6 from the parent study) HT-hSBA titers ≥ LLQ, an increase of at least two times the pre-vaccination HT-hSBA titers.
Time Frame	At Months 7 and 10 (1 and 4 months after the 3-dose vaccination series)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the FAS-Immunogenicity (months 7 and 10)- included all screened subjects who provided consent & demographic &/baseline screening assessments, received a subjects D & vaccination, & provided evaluable serum samples at months 7 & 10 & whose immunogenicity assay result was available for at least one serogroup B strain.

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	90	90
96217 (Month 7)	87	12
M07-0241084 (Month 7)	38	1
M14459 (Month 7)	67	0
NZ98/254 (Month 7)	56	0
96217 (Month 10)	54	7
M07-0241084 (Month 10)	0	4
M14459 (Month 10)	7	0
NZ98/254 (Month 10)	13	0

10. Secondary Outcome

Title	Percentages of Subjects With a Three-fold Rise in HT-hSBA Titers Against the N. Meningitidis Serogroup B Test Strains at 1 and 4 Months After the 3-dose Vaccination Series.
Description	The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with a three-fold rise in HT-hSBA titers against the N. meningitidis serogroup B test strains, at 1 and 4 months after the 3-dose vaccination series. The three-fold titers rise is defined as: a) for subjects with pre-vaccination (Month 6 from the parent study) HT-hSBA titers < LLQ, postvaccination HT-hSBA titers ≥ 3 LLQ; b) for subjects with pre-vaccination (Month 6 from the parent study) HT-hSBA titers ≥ LLQ, an increase of at least three times the pre-vaccination HT-hSBA titers.
Time Frame	At months 7 and 10 (1 and 4 months after 3-dose vaccination series)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the FAS-Immunogenicity (months 7 and 10)- included all screened subjects who provided consent & demographic &/baseline screening assessments, received a subject ID & vaccination, & provided evaluable serum samples at months 7 & 10 & whose immunogenicity assay result was available for at least one serogroup B strain.

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	90	90
96217 (Month 7)	79	5
M07-0241084 (Month 7)	23	1
M14459 (Month 7)	41	0
NZ98/254 (Month 7)	41	0
96217 (Month 10)	27	5
M07-0241084 (Month 10)	0	2
M14459 (Month 10)	3	0
NZ98/254 (Month 10)	5	0

11. Secondary Outcome

Title	Percentages of Subjects With a Four-fold Rise in HT-hSBA Titers Against the N. Meningitidis Serogroup B Test Strains at 1 and 4 Months After the 3-dose Vaccination Series.
Description	The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with a four-fold rise in HT-hSBA titers against the N. meningitidis serogroup B test strains, at 1 and 4 months after the 3-dose vaccination series. The four-fold titers rise is defined as: a) for subjects with pre-vaccination (Month 6 from the parent study) HT-hSBA titers < LLQ, postvaccination HT-hSBA titers ≥ 4 LLQ; b) for subjects with pre-vaccination (Month 6 from the parent study) HT-hSBA titers ≥ LLQ, an increase of at least four times the pre-vaccination HT-hSBA titers.
Time Frame	At Months 7 and 10 (1 and 4 months after the 3-dose vaccination series)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS-Immunogenicity (Months 7 &10)- included all screened subjects who provided consent & demographic &/or baseline screening assessments, received a subject ID & vaccination, & provided evaluable serum samples at Months 7 & 10 & whose immunogenicity assay result was available for at least one serogroup B test strain.

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	90	90
96217 (Month 7)	63	3
M07-0241084 (Month 7)	12	0
M14459 (Month 7)	23	0
NZ98/254 (Month 7)	33	0
96217 (Month 10)	15	5
M07-0241084 (Month 10)	0	1
M14459 (Month 10)	3	0
NZ98/254 (Month 10)	2	0

12. Secondary Outcome

Title	HT-hSBA GMTs Against N. Meningitidis Serogroups A, C, W and Y.
Description	The immunogenicity of three doses of MenABCWY compared to a single dose of MenACWY vaccine, in terms of HT-hSBA GMTs to serogroups A, C, W, and Y, at 1 and 4 months after the 3-dose vaccination series.
Time Frame	At Months 7 and 10 (1 and 4 months after the 3-dose vaccination series)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS-Immunogenicity (Months 7 &10)- included all screened subjects who provided consent & demographic &/or baseline screening assessments, received a subject ID & vaccination, & provided evaluable serum samples at Months 7 & 10 & whose immunogenicity assay result was available for at least one serogroup B test strain.

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	91	91
Men A, Month 7	127.92	3.37
Men A, Month 10	36.5	2.73
Men C, Month 7	521.64	18.34
Men C, Month 10	291.19	15.4
Men W, Month 7	424.8	40.22
Men W, Month 10	147.4	23.01
Men Y, Month 7	204.84	13.27
Men Y, Month 10	83.42	11.85

13. Secondary Outcome

Title	Percentages of Subjects With HT-hSBA Titers Against the N. Meningitidis Serogroup A, C, W and Y ≥ LLQ at 1 Month After the 3- Dose Vaccination Series
Description	The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with HT-hSBA titers ≥ LLQ against serogroups A, C, W, Y, at 1 month after the 3-dose vaccination series.The LLQ cut off values for serogroups A,C,W and Y were 22.7,5.2, 39.6 and 14.7 respectively.
Time Frame	At Month 7 (1 month after the 3-dose vaccination series)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS-Immunogenicity (Month 7)- included all screened subjects who provided consent & demographic &/or baseline screening assessments, received a subject ID & vaccination, & provided evaluable serum samples at Month 7 & whose immunogenicity assay result was available for at least one serogroup A, C, W and Y test strain.

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	91	88
Men A	98	24
Men C	100	73
Men W	99	60
Men Y	100	57

14. Secondary Outcome

Title	Percentages of Subjects With HT-hSBA Titers Against the N. Meningitidis Serogroup A, C, W and Y ≥ LLQ at 4 Months After the 3-dose Vaccination Series
Description	The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with HT-hSBA titers ≥ LLQ against serogroups A, C, W, Y, at 4 months after the 3-dose vaccination series. The LLQ cut off values for serogroups A, C, W and Y were 22.7,5.2,39.6 and 14.7 respectively.
Time Frame	At Month 10 (4 months after the 3-dose vaccination series)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS-Immunogenicity (Month 10)- included all screened subjects who provided informed consent & demographic &/or baseline screening assessments, received a subject ID & vaccination, & provided evaluable serum samples at Month 10 and whose immunogenicity assay result was available for at least one serogroup B strain

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	86	91
Men A	81	18
Men C	100	69
Men W	89	51
Men Y	86	53

15. Secondary Outcome

Title	Percentage of Subjects With Two-fold Rise in HT-hSBA Titers Against the N. Meningitidis Serogroups A, C,W and Y at 1 and 4 Months After the 3-dose Vaccination Series.
Description	The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with a two-fold rise in HT-hSBA titers against the N. meningitidis serogroups A, C, W and Y at 1 and 4 months after the 3-dose vaccination series. The two-fold titers rise is defined as: a) for subjects with pre-vaccination (Month 6 from the parent study) HT-hSBA titers < LLQ, postvaccination HT-hSBA titers ≥ 2 LLQ; b) for subjects with pre-vaccination (Month 6 from the parent study) HT-hSBA titers ≥ LLQ, an increase of at least two times the pre-vaccination HT-hSBA titers.
Time Frame	At Months 7 and 10 (1 and 4 months after the 3-dose vaccination series)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the FAS-Immunogenicity (months 7 and 10)- included all screened subjects who provided consent & demographic &/baseline screening assessments, received a subject ID & vaccination, & provided evaluable serum samples at months 7 & 10 & whose immunogenicity assay result was available for at least one serogroup B strain.

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	89	88
Men A, Month 7	88	2
Men C, Month 7	87	2
Men W, Month 7	83	5
Men Y, Month 7	57	2
Men A, Month 10	32	1
Men C, Month 10	56	8
Men W, Month 10	24	1
Men Y, Month 10	26	3

16. Secondary Outcome

Title	Percentage of Subjects With Three-fold Rise in HT-hSBA Titers Against the N. Meningitidis Serogroups A, C, W and Y at 1 and 4 Months After the 3-dose Vaccination Series.
Description	The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with a three-fold rise in HT-hSBA titers against the N. meningitidis serogroups A, C, W and Y, at 1 and 4 months after the 3-dose vaccination series. The three-fold titers rise is defined as: a) for subjects with pre-vaccination (Month 6 from the parent study) HT-hSBA titers < LLQ, postvaccination HT-hSBA titers ≥ 3 LLQ; b) for subjects with pre-vaccination (Month 6 from the parent study) HT-hSBA titers ≥ LLQ, an increase of at least three times the pre-vaccination HT-hSBA titers.
Time Frame	At Months 7 and 10 (1 and 4 months after the 3-dose vaccination series)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS-Immunogenicity (Months 7 &10)- included all screened subjects who provided consent & demographic &/or baseline screening assessments, received a subject ID & vaccination, & provided evaluable serum samples at Months 7 & 10 & whose immunogenicity assay result was available for at least one serogroup B test strain.

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	89	88
Men A, Month 7	69	0
Men C, Month 7	60	1
Men W, Month 7	67	0
Men Y, Month 7	39	0
Men A, Month 10	16	1
Men C, Month 10	29	5
Men W, Month 10	13	0
Men Y, Month 10	15	2

17. Secondary Outcome

Title	Percentage of Subjects With Four-fold Rise in HT-hSBA Titers Against the N. Meningitidis Serogroups A, C, W and Y at 1 and 4 Months After the 3-dose Vaccination Series.
Description	The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with a four-fold rise in HT-hSBA titers against the N. meningitidis serogroups A, C, W and Y, at 1 and 4 months after the 3-dose vaccination series. The four-fold titers rise is defined as: a) for subjects with pre-vaccination (Month 6 from the parent study) HT-hSBA titers < LLQ, postvaccination HT-hSBA titers ≥ 4 LLQ; b) for subjects with pre-vaccination (Month 6 from the parent study) HT-hSBA titers ≥ LLQ, an increase of at least four times the pre-vaccination HT-hSBA titers.
Time Frame	At Months 7 and 10 (1 and 4 months after the 3-dose vaccination series)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS-Immunogenicity (Months 7 &10)- included all screened subjects who provided consent & demographic &/or baseline screening assessments, received a subject ID & vaccination, & provided evaluable serum samples at Months 7 & 10 & whose immunogenicity assay result was available for at least one serogroup B test strain.

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	89	88
Men A, Month 7	53	0
Men C, Month 7	49	1
Men W, Month 7	49	0
Men Y, Month 7	28	0
Men A, Month 10	6	1
Men C, Month 10	21	2
Men W, Month 10	8	0
Men Y, Month 10	6	1

18. Secondary Outcome

Title	Percentages of Subjects With HT-hSBA Titers Against N. Meningitidis Serogroup B Test Strains≥ 5, ≥ 8, ≥ 16, ≥ 32, ≥ 64, ≥ 128 at 1 Month After the 3-dose Vaccination Series
Description	The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of percentages of subjects with HT-hSBA titers ≥ 5, ≥ 8, ≥ 16, ≥ 32, ≥ 64, ≥ 128 against serogroup N. meningitidis B test strains (M14459, M07-0241084, 96217 and NZ98/254), at 1 month after the 3-dose vaccination series.
Time Frame	At Month 7 (1 month after the 3-dose vaccination series)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS-Immunogenicity (Month 7)- included all screened subjects who provided consent & demographic &/or baseline screening assessments, received a subject ID & vaccination, & provided evaluable serum samples at Month 7 & whose immunogenicity assay result was available for at least one serogroup B test strain.

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	91	90
96217, ≥ 5	100	38
96217, ≥ 8	100	37
96217, ≥ 16	100	25
96217, ≥ 32	100	15
96217, ≥ 64	99	8
96217, ≥ 128	93	3
M07-0241084, ≥ 5	82	16
M07-0241084, ≥ 8	67	12
M07-0241084, ≥ 16	46	8
M07-0241084, ≥ 32	20	3
M07-0241084, ≥ 64	6	2
M07-0241084, ≥ 128	0	0
M14459, ≥ 5	95	1
M14459, ≥ 8	90	1
M14459, ≥ 16	71	1
M14459, ≥ 32	34	1
M14459, ≥ 64	11	0
M14459, ≥ 128	3	0
NZ98/254, ≥ 5	89	1
NZ98/254, ≥ 8	79	1
NZ98/254, ≥ 16	61	0
NZ98/254, ≥ 32	37	0
NZ98/254, ≥ 64	10	0
NZ98/254, ≥ 128	4	0

19. Secondary Outcome

Title	Percentages of Subjects With HT-hSBA Titers Against N. Meningitidis Serogroup B Test Strains ≥ 5, ≥ 8, ≥ 16, ≥ 32, ≥ 64, ≥ 128 at 4 Months After the 3-dose Vaccination Series
Description	The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of percentages of subjects with HT-hSBA titers ≥ 5, ≥ 8, ≥ 16, ≥ 32, ≥ 64, ≥ 128 against serogroup N. meningitidis B test strains (M14459, M07-0241084, 96217 and NZ98/254), at 4 months after the 3-dose vaccination series.
Time Frame	At Month 10 (4 months after the 3-dose vaccination series)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS-Immunogenicity (Month 10)- included all screened subjects who provided consent & demographic &/or baseline screening assessments, received a subject ID & vaccination, & provided evaluable serum samples at Month 10 & whose immunogenicity assay result was available for at least one serogroup B test strain.

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	88	91
96217, ≥ 5	99	35
96217, ≥ 8	99	33
96217, ≥ 16	98	21
96217, ≥ 32	94	16
96217, ≥ 64	85	6
96217, ≥ 128	56	2
M07-0241084, ≥ 5	38	17
M07-0241084, ≥ 8	24	12
M07-0241084, ≥ 16	9	9
M07-0241084, ≥ 32	1	3
M07-0241084, ≥ 64	1	2
M07-0241084, ≥ 128	0	1
M14459, ≥ 5	49	4
M14459, ≥ 8	36	3
M14459, ≥ 16	17	1
M14459, ≥ 32	6	0
M14459, ≥ 64	1	0
M14459, ≥ 128	0	0
NZ98/254, ≥ 5	44	1
NZ98/254, ≥ 8	34	1
NZ98/254, ≥ 16	16	0
NZ98/254, ≥ 32	5	0
NZ98/254, ≥ 64	2	0
NZ98/254, ≥ 128	2	0

20. Secondary Outcome

Title	Percentages of Subjects With HT-hSBA Titers Against the N. Meningitidis Serogroup A, C, W and Y ≥ 8, ≥ 16, ≥ 32, ≥ 64, ≥128 at 1 Month After the 3- Dose Vaccination Series
Description	The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with HT-hSBA titers ≥ 8, ≥ 16, ≥ 32, ≥ 64, ≥128 against serogroups A, C, W, Y, at 1 month after the 3-dose vaccination series.
Time Frame	At Month 7 (1 month after the 3-dose vaccination series)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS-Immunogenicity (Month 7)- included all screened subjects who provided consent & demographic &/or baseline screening assessments, received a subject ID & vaccination, & provided evaluable serum samples at Month 7 & whose immunogenicity assay result was available for at least one serogroup A, C, W and Y test strain.

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	91	88
Men A, ≥ 8	98	30
Men A, ≥ 16	98	26
Men A, ≥ 32	98	22
Men A, ≥ 64	86	13
Men A, ≥ 128	56	8
Men C, ≥ 8	100	71
Men C, ≥ 16	99	51
Men C, ≥ 32	99	33
Men C, ≥ 64	99	26
Men C, ≥ 128	91	19
Men W, ≥ 8	100	86
Men W, ≥ 16	100	77
Men W, ≥ 32	99	61
Men W, ≥ 64	99	45
Men W, ≥ 128	89	24
Men Y, ≥ 8	100	61
Men Y, ≥ 16	100	56
Men Y, ≥ 32	95	44
Men Y, ≥ 64	81	27
Men Y, ≥ 128	65	14

21. Secondary Outcome

Title	Percentages of Subjects With HT-hSBA Titers Against the N. Meningitidis Serogroup A, C, W and Y ≥8, ≥ 16, ≥ 32, ≥ 64, ≥128 at 4 Months After the 3-dose Vaccination Series
Description	The immunogenicity of three doses of MenABCWY vaccine compared to a single dose of MenACWY, in terms of the percentages of subjects with HT-hSBA titers≥ 8, ≥ 16, ≥ 32, ≥ 64, ≥ 128 against serogroups A, C, W, Y, at 4 months after the 3-dose vaccination series.
Time Frame	At Month 10 (4 months after the 3-dose vaccination series)

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS-Immunogenicity (Month 10)- included all screened subjects who provided consent & demographic &/or baseline screening assessments, received a subject ID & vaccination, & provided evaluable serum samples at Month 10 & whose immunogenicity assay result was available for at least one serogroup A, C, W and Y test strain.

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	86	91
Men A, ≥ 8	86	25
Men A, ≥ 16	84	23
Men A, ≥ 32	72	18
Men A, ≥ 64	46	8
Men A, ≥128	14	7
Men C, ≥ 8	100	65
Men C, ≥ 16	98	48
Men C, ≥ 32	97	34
Men C, ≥ 64	86	26
Men C, ≥ 128	74	16
Men W, ≥ 8	99	75
Men W, ≥ 16	98	66
Men W, ≥ 32	94	58
Men W, ≥ 64	75	36
Men W, ≥ 128	52	18
Men Y, ≥ 8	91	58
Men Y, ≥ 16	86	51
Men Y, ≥ 32	77	38
Men Y, ≥ 64	62	20
Men Y, ≥ 128	40	9

22. Secondary Outcome

Title	Number of Subjects Reporting Any Solicited Local or Systemic Adverse Events (AEs)
Description	Number of subjects reporting any solicited local or systemic AEs from Day 1 (6 hours) to Day 7 after any meningococcal vaccination is reported. Assessed solicited local symptoms were induration, erythema and pain. Assessed solicited general symptoms were fatigue, myalgia, arthralgia, headache, fever, chills and loss of appetite. Other solicited data included prevention of pain/fever and treatment of pain/fever. Any = occurrence of the symptom regardless of intensity grade.
Time Frame	Day 1 (6 hours) to Day 7 after vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety Set (solicited AEs & other solicited reactions)-included all screened subjects who provided consent & demographic &/or baseline screening assessments, received a subject ID & a study vaccination, & provided post-vaccination reactogenicity data.

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	90	87
Any	62 65.3%	25 26.6%
Any Local Reactions	60 63.2%	15 16%
Any Systemic Reactions	27 28.4%	15 16%
Induration (mm)	6 6.3%	0 0%
Erythema (mm)	6 6.3%	0 0%
Pain	59 62.1%	15 16%
Nausea	5 5.3%	5 5.3%
Fatigue	14 14.7%	11 11.7%
Myalgia	13 13.7%	3 3.2%
Arthralgia	9 9.5%	0 0%
Headache	13 13.7%	9 9.6%
Fever	0 0%	1 1.1%
Chills	2 2.1%	3 3.2%
Loss of appetite	3 3.2%	3 3.2%
Prevention of pain/fever	0 0%	0 0%
Treatment of pain/fever	12 12.6%	3 3.2%

23. Secondary Outcome

Title	Number of Subjects Reporting Any Unsolicited AEs
Description	The number of subjects reporting unsolicited AEs after any vaccination is reported. An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Time Frame	Day 1 to Day 30 after any vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety set (unsolicited AEs)- included all screened subjects who provided informed consent & demographic and/or baseline screening assessments, received a subject ID and a study vaccination, and had post-vaccination unsolicited adverse event records.

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	93	93
Count of Participants [Participants]	14 14.7%	11 11.7%

24. Secondary Outcome

Title	Number of Subjects Reporting Any Serious Adverse Events (SAEs), Medically-attended AEs and AEs Leading to Premature Withdrawal.
Description	The number of subjects reporting any SAEs, medically-attended AEs and AEs leading to premature withdrawal during the entire study period is reported. SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. MAEs were defined as events for which the subject received medical attention defined as hospitalization, an emergency room visit, or a visit to or from medical personnel (medical doctor) for any reason. Any was defined as the occurrence of any unsolicited AE regardless of intensitygrade or relation to vaccination.
Time Frame	During the entire study period (from Day 0 up to Month 10)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety Set (overall)- included all screened subjects who provide informed consent and demographic and/or baseline screening assessments, received a subject ID and a study vaccination, and have either post-vaccination reactogenicity data or post-vaccination unsolicited adverse event records.

Arm/Group Title	MenABCWY Group	MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.	Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
Measure Participants	95	94
Any SAEs	0 0%	0 0%
Any Medically Attended AEs	14 14.7%	20 21.3%
Any AEs leading to premature withdrawal	0 0%	0 0%

Adverse Events

Time Frame	Solicited local and general AEs were collected from Day 1 to Day 7. Unsolicited AEs were collected from Day 1 to Day 30. SAEs, medically-attended AEs and AEs leading to withdrawal are collected for the entire duration of the study (from Day 0 to Month 10).
Adverse Event Reporting Description	Data are presented in terms of number of subjects reporting AEs. The total number of subjects at risk for the frequent adverse events were analysed from the exposed set and the number of subjects at risk for each of the adverse event were analysed from the overall safety set. Therefore, the number of subjects at risk for each adverse event is lesser than the total number of subjects at risk.
Arm/Group Title	MenABCWY Group		MenACWY Group
Arm/Group Description	Subjects who received 2 doses of MenABCWY vaccine in the parent study and a 3rd dose of MenABCWY vaccine in the current study.		Subjects who received 1 dose of placebo and 1 dose of MenACWY vaccine in the parent study and 1 dose of placebo in the current study.
All Cause Mortality
	MenABCWY Group		MenACWY Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/95 (0%)		0/94 (0%)
Serious Adverse Events
	MenABCWY Group		MenACWY Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/95 (0%)		0/94 (0%)
Other (Not Including Serious) Adverse Events
	MenABCWY Group		MenACWY Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	63/95 (66.3%)		27/94 (28.7%)
Gastrointestinal disorders
Nausea	5/93 (5.4%)	9	5/93 (5.4%)	7
General disorders
Fatigue	14/93 (15.1%)	32	11/93 (11.8%)	24
Injection site erythema	16/93 (17.2%)	44	4/93 (4.3%)	12
Injection site induration	16/93 (17.2%)	57	3/93 (3.2%)	10
Injection site pain	60/93 (64.5%)	155	15/93 (16.1%)	23
Infections and infestations
Upper respiratory tract infection	6/93 (6.5%)	6	1/93 (1.1%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	9/93 (9.7%)	21	1/93 (1.1%)	1
Myalgia	13/93 (14%)	33	3/93 (3.2%)	10
Nervous system disorders
Headache	14/93 (15.1%)	25	9/93 (9.7%)	27

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.