Trial to Assess Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Meningococcal ABCWY Vaccine as Compared to Meningococcal B Vaccine in Adolescents

Study Overview
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Brief Summary
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The main purposes for conducting the study are firstly to assess immunological non-inferiority of the MenABCWY vaccine, administered according to 0, 2 month schedule to healthy adolescents 10 to 18 years of age, to those of the licensed rMenB+OMV vaccine (Bexsero™) in terms of hSBA GMTs at one month after the second vaccination, secondly to give the flexibility for the national vaccination program by showing the safety and immunogenicity of MenABCWY administrated according to four different vaccination schedules and additionally to evaluate a potential benefit of the 3-dose vaccination series.

Official Title
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A Phase 2b, Randomized, Controlled, Observer-Blind, Multi-Center Study Assessing the Immunogenicity and Safety of GSK Meningococcal ABCWY Vaccine Administered at Different Schedules Compared to GSK Meningococcal Group B Vaccine, in Healthy Adolescents

Conditions
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Infections, Meningococcal

Intervention / Treatment
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* Biological: Bexsero
* Other: Saline Placebo
* Biological: Havrix
* Biological: MenABCWY


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adolecents from 10-18 yearsof age, generally in good health, and available for all study visits, and who/whose legally acceptable representative has given written informed consent at the time of enrollment. Individuals of who the investigator believes can and will comply with the requirements of the protocol (e.g. use of an eDiary, return for follow-up visits, available for phone contacts). Female subjects of childbearing potential must have a negative urine preganancy test. Exclusion Criteria: Serious, acute, or chronic illness. Previous or suspected disease caused by N. meningitidis. Previous immunization with any menincococcal or Hepatitis A vaccines. Exposure to individuals with clicically proven meningococcal disease or clinical bacterial meningitis without further microbiologic characteriszation.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rMenB_0_2 Group<br>Subjects received two injections of Bexsero vaccine at Visit Month 0 and Visit Month 2, Havrix vaccine at Visit Month 6 and Visit Month 12 and saline placebo at Visit Month 1. | Biological: Bexsero<br>* Two doses administered intramuscularly into the deltoid area at Months 0 and 2 in rMenB_0_2 Group.<br>Other: Saline Placebo<br>* One dose administered intramusculary in the deltoid muscle at Month 1 in ABCWY_ 0_2 Group and rMenB_0_2 Group, Month 2 in ABCWY_0_6 Group and ABCWY_0_11 Group and Month 6 in ABCWY_0_1 Group.<br>Biological: Havrix<br>* Two doses administered in the deltoid muscle at Month 2 and 12 in ABCWY_0_1 Group, Month 1 and 12 in Group ABCWY_0_6 Group and ABCWY_0_2_6 Group , Month 0 and 6 in ABCWY_0_11 Group and Month 6 and 12 in ABCWY_ 0_2 Group and rMenB_0_2 Group.<br>|
| Experimental: ABCWY_ 0_2 Group<br>Subjects received MenABCWY vaccine at Visit Month 0 and Visit Month 2, Havrix vaccine at Visit Month 6 and Visit Month 12 and saline placebo at Visit Month 1. | Other: Saline Placebo<br>* One dose administered intramusculary in the deltoid muscle at Month 1 in ABCWY_ 0_2 Group and rMenB_0_2 Group, Month 2 in ABCWY_0_6 Group and ABCWY_0_11 Group and Month 6 in ABCWY_0_1 Group.<br>Biological: Havrix<br>* Two doses administered in the deltoid muscle at Month 2 and 12 in ABCWY_0_1 Group, Month 1 and 12 in Group ABCWY_0_6 Group and ABCWY_0_2_6 Group , Month 0 and 6 in ABCWY_0_11 Group and Month 6 and 12 in ABCWY_ 0_2 Group and rMenB_0_2 Group.<br>Biological: MenABCWY<br>* Two to three doses administered in the deltoid muscle at Month 0 and 1 in ABCWY_0_1 Group, Month 0 and 6 in ABCWY_0_6 Group, Month 1 and 12 in ABCWY_0_11 Group, Month 0, 2 and 6 in ABCWY_0_2_6 Group, Month 0 and 2 in ABCWY_ 0_2 Group and rMenB_0_2 Group.<br>|
| Experimental: ABCWY_0_1 Group<br>Subjects received MenABCWY vaccine at Visit Month 0 and Visit Month 1, Havrix vaccine at Visit Month 2 and Visit Month 12 and saline placebo at Visit Month 6. | Other: Saline Placebo<br>* One dose administered intramusculary in the deltoid muscle at Month 1 in ABCWY_ 0_2 Group and rMenB_0_2 Group, Month 2 in ABCWY_0_6 Group and ABCWY_0_11 Group and Month 6 in ABCWY_0_1 Group.<br>Biological: Havrix<br>* Two doses administered in the deltoid muscle at Month 2 and 12 in ABCWY_0_1 Group, Month 1 and 12 in Group ABCWY_0_6 Group and ABCWY_0_2_6 Group , Month 0 and 6 in ABCWY_0_11 Group and Month 6 and 12 in ABCWY_ 0_2 Group and rMenB_0_2 Group.<br>Biological: MenABCWY<br>* Two to three doses administered in the deltoid muscle at Month 0 and 1 in ABCWY_0_1 Group, Month 0 and 6 in ABCWY_0_6 Group, Month 1 and 12 in ABCWY_0_11 Group, Month 0, 2 and 6 in ABCWY_0_2_6 Group, Month 0 and 2 in ABCWY_ 0_2 Group and rMenB_0_2 Group.<br>|
| Experimental: ABCWY_0_6 Group<br>Subjects received MenABCWY vaccine at Visit Month 0 and Visit Month 6, Havrix vaccine at Visit Month 1 and Visit Month 12 and saline placebo at Visit Month 2. | Other: Saline Placebo<br>* One dose administered intramusculary in the deltoid muscle at Month 1 in ABCWY_ 0_2 Group and rMenB_0_2 Group, Month 2 in ABCWY_0_6 Group and ABCWY_0_11 Group and Month 6 in ABCWY_0_1 Group.<br>Biological: Havrix<br>* Two doses administered in the deltoid muscle at Month 2 and 12 in ABCWY_0_1 Group, Month 1 and 12 in Group ABCWY_0_6 Group and ABCWY_0_2_6 Group , Month 0 and 6 in ABCWY_0_11 Group and Month 6 and 12 in ABCWY_ 0_2 Group and rMenB_0_2 Group.<br>Biological: MenABCWY<br>* Two to three doses administered in the deltoid muscle at Month 0 and 1 in ABCWY_0_1 Group, Month 0 and 6 in ABCWY_0_6 Group, Month 1 and 12 in ABCWY_0_11 Group, Month 0, 2 and 6 in ABCWY_0_2_6 Group, Month 0 and 2 in ABCWY_ 0_2 Group and rMenB_0_2 Group.<br>|
| Experimental: ABCWY_0_11 Group<br>Subjects received MenABCWY vaccine at Visit Month 1 and Visit Month 12, Havrix vaccine at Visit Month 0 and Visit Month 6 and saline placebo at Visit Month 2. | Other: Saline Placebo<br>* One dose administered intramusculary in the deltoid muscle at Month 1 in ABCWY_ 0_2 Group and rMenB_0_2 Group, Month 2 in ABCWY_0_6 Group and ABCWY_0_11 Group and Month 6 in ABCWY_0_1 Group.<br>Biological: Havrix<br>* Two doses administered in the deltoid muscle at Month 2 and 12 in ABCWY_0_1 Group, Month 1 and 12 in Group ABCWY_0_6 Group and ABCWY_0_2_6 Group , Month 0 and 6 in ABCWY_0_11 Group and Month 6 and 12 in ABCWY_ 0_2 Group and rMenB_0_2 Group.<br>Biological: MenABCWY<br>* Two to three doses administered in the deltoid muscle at Month 0 and 1 in ABCWY_0_1 Group, Month 0 and 6 in ABCWY_0_6 Group, Month 1 and 12 in ABCWY_0_11 Group, Month 0, 2 and 6 in ABCWY_0_2_6 Group, Month 0 and 2 in ABCWY_ 0_2 Group and rMenB_0_2 Group.<br>|
| Experimental: ABCWY_0_2_6 Group<br>Subjects received MenABCWY vaccine at Visit Month 0, Visit Month 2 and Visit Month 6 and Havrix vaccine at Visit Month 1 and Visit Month 12. | Biological: Havrix<br>* Two doses administered in the deltoid muscle at Month 2 and 12 in ABCWY_0_1 Group, Month 1 and 12 in Group ABCWY_0_6 Group and ABCWY_0_2_6 Group , Month 0 and 6 in ABCWY_0_11 Group and Month 6 and 12 in ABCWY_ 0_2 Group and rMenB_0_2 Group.<br>Biological: MenABCWY<br>* Two to three doses administered in the deltoid muscle at Month 0 and 1 in ABCWY_0_1 Group, Month 0 and 6 in ABCWY_0_6 Group, Month 1 and 12 in ABCWY_0_11 Group, Month 0, 2 and 6 in ABCWY_0_2_6 Group, Month 0 and 2 in ABCWY_ 0_2 Group and rMenB_0_2 Group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Human Serum Bactericidal Assay (hSBA) Geometric Mean Titers (GMTs) Against N. Meningitidis Serogroup B Test Strains When Administered According to 0_2 Month Schedule. | The non-inferiority of the Meningococcal (groups A, C, W and Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant (MenABCWY) vaccine to Meningococcal (group B) multicomponent recombinant adsorbed (Bexsero) vaccine, administered according to 0, 2 month schedule, as measured by hSBA GMTs against N.meningitidis serogroup B test strains at 1 month after the last meningococcal vaccination, is reported. The test strains assessed were Meningitis B NZ98/254 Ab, Meningitis B M14459 Ab, Meningitis B M07-0241084 Ab and Meningitis B 96217 Ab. This outcome measure was evaluated in the rMenB_0_2 and ABCWY_ 0_2 Groups. | At baseline (Month 0) and 1 month after the last meningococcal vaccination (Month 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hSBA GMTs Against N. Meningitidis Serogroups A, C, W and Y and Serogroup B Test Strains When Administered According to 0_2_6 Month and 0_2 Month Schedule. | The immunogenicity of MenABCWY vaccine, administered according to 0, 2, 6 months schedule was compared with those administered according to 0, 2 months schedule, as measured by hSBA GMTs against N. meningitidis serogroup B test strains and serogroups A,C, W and Y at 1 month after the last meningococcal vaccination. The B test strains assessed were Meningitis B NZ98/254 Ab, Meningitis B M14459 Ab, Meningitis B M07-0241084 Ab and Meningitis B 96217 Ab. This outcome measure was evaluated in the ABCWY_ 0_2 and ABCWY_0_2_6 Groups. 1 month post last meningococcal vaccination corresponds to Month 3 for ABCWY_0_2 Group and Month 7 for ABCWY_0_2_6 Group. | At baseline (Month 0) and 1 month after the last meningococcal vaccination (Month 3 for ABCWY_ 0_2 Group and Month 7 for ABCWY_0_2_6 Group) | 
| Percentages of Subjects With hSBA Titers ≥LLQ Against N. Meningitidis Serogroups A, C, W and y and Serogroup B Test Strains When Administered According to 0_2_6 Month and 0_2 Month Schedule. | The immunogenicity of MenABCWY vaccine, administered according to 0, 2, 6 month schedule, was compared with those, administered according to 0, 2 month schedule, as measured by the percentages of subjects with hSBA titers ≥ LLQ against N. meningitidis serogroup B test strains at 1 month after the last meningococcal vaccination. | At baseline (Month 0) and 1 month after the last meningococcal vaccination (Month 3 for ABCWY_ 0_2 Group and Month 7 for ABCWY_0_2_6 Group) | 
| hSBA GMTs Against Each of N. Meningitidis Serogroups A, C, W and Y and Serogroup B Test Strains When Administered According to 0_1 Month, 0_2 Month, 0_6 Month and 0, 11 Month Schedule. | The immunogenicity of MenABCWY vaccine, administered according to 0, 2 months schedule, was compared with those, administered according to 0, 1 month, 0, 6 month and 0, 11 month schedules as measured by hSBA GMTs against N. meningitidis serogroups A, C, W and Y and serogroup B test strains at 1 month after the second meningococcal vaccination. | At 1 Month after the last vaccination (Month 2 for ABCWY_0_1 Group, Month 3 for ABCWY_0_2 Group, Month 7 for ABCWY_0_6 Group and Month 13 for ABCWY_0_11 Group) | 
| Percentages of Subjects With hSBA Titers ≥ Lower Limit of Quantitation (LLQ) Against N. Meningitidis Serogroup B Test Strains When Administered According to 0_2 Month Schedule. | A sufficient immune response following Bexsero vaccine, administered according to 0, 2 month schedule, as measured by the percentage of subjects with hSBA titers ≥ Lower Limit of Quantitation (LLQ) against N. meningitidis serogroup B test strains at 1 month after the last meningococcal vaccination, was to be demonstrated. Criterion: the immune response was to be considered sufficient if the lower limit of the two-sided 95% CI for the percentage of subjects with hSBA titers ≥ LLQ was greater than 75% for each of the four serogroup B test strains. The test strains assessed were Meningitis B NZ98/254 Ab, Meningitis B M14459 Ab, Meningitis B M07-0241084 Ab and Meningitis B 96217 Ab. | At baseline (Month 0) and 1 month after the last meningococcal vaccination (Month 3) | 
| hSBA GMTs Against N. Meningitidis Serogroups A, C, W and Y and Serogroup B Test Strains When Administered According to 0_2_6 Month and 0_6 Month Schedule. | The immunogenicity of MenABCWY vaccine, administered according to 0, 2, 6 months schedule was compared with those administered according to 0, 6 months schedule, as measured by hSBA GMTs against N. meningitidis serogroups A, C, W and Y and serogroup B test strains at 1 month after the last meningococcal vaccination. | At 1 month after last vaccination (Month 7) | 
| Percentages of Subjects With hSBA Titers ≥ Lower Limit of Quantitation (LLQ) Against Serogroups A, C, W and Y and Serogroup B Test Strains When Administered According to 0_2_6 Month and 0_6 Month Schedule. | The immunogenicity of MenABCWY vaccine, administered according to 0, 2, 6 month schedule, was compared with those, administered according to 0, 6 month schedule, as measured by the percentages of subjects with hSBA titers ≥ LLQ against serogroups A, C, W and Y and serogroup B test strains at 1 month after the last meningococcal vaccination. | At baseline (Month 0) and 1 month after the last meningococcal vaccination (Month 7) | 
| Percentages of Subjects With hSBA Titers ≥ LLQ Against N. Meningitidis Serogroups A, C, W and Y and Serogroup B Test Strains When Administered According to 0_1 Month, 0_2 Month, 0_6 Month and 0_11 Month Schedule. | The immunogenicity of MenABCWY vaccine, administered according to 0, 2 month schedule, was compared with those, administered according to 0, 1 month, 0, 6 month and 0, 11 month schedules, as measured by the percentages of subjects with hSBA titers ≥ LLQ against N. meningitidis serogroups A, C, W and Y and serogroup B test strains at 1 month after the second meningococcal vaccination. | At 1 month after second vaccination (Month 2 for ABCWY_0_1 Group, Month 3 for ABCWY_0_2 Group , Month 7 for ABCWY_0_6 Group and Month 13 for ABCWY_0_11 Group) | 
| hSBA GMTs Against Serogroups A, C, W and Y and Serogroup B Test Strains at All the Relevant Time Points for All Schedules. | The kinetic of immune response (at Months 0, 2, 3, 7 and 13) following different vaccination schedules as measured by the adjusted hSBA GMTs against serogroups A,C, W and Y and serogroup B test strains was assessed. | At Month 0, Month 2, Month 3, Month 7 and Month 13 | 
| Percentages of Subjects With hSBA Titers ≥LLQ, ≥5, ≥8, ≥16, ≥32, ≥64, ≥128 Against NZ98/254 B Strain for All Schedules. | The kinetic of immune response (at Months 0, 2, 3, 7 and 13) following different vaccination schedules as measured by the percentages of subjects with hSBA titers ≥LLQ, ≥5, ≥8, ≥16, ≥32, ≥64, ≥128 against NZ98/254 B strain was assessed. | At Month 0, Month 2, Month 3, Month 7 and Month 13. | 
| Percentages of Subjects With hSBA Titers ≥LLQ, ≥5, ≥8, ≥16, ≥32, ≥64, ≥128 Against M14459 B Strain for All Schedules. | The kinetic of immune response (at Months 0, 2, 3, 7 and 13) following different vaccination schedules as measured by the percentages of subjects with hSBA titers ≥LLQ, ≥5, ≥8, ≥16, ≥32, ≥64, ≥128 against M14459 B strain was assessed. | At Month 0, Month 2, Month 3, Month 7 and Month 13. | 
| Percentages of Subjects With hSBA Titers ≥LLQ, ≥5, ≥8, ≥16, ≥32, ≥64, ≥128 Against M07-0241084 B Strain for All Schedules. | The kinetic of immune response (at Months 0, 2, 3, 7 and 13) following different vaccination schedules as measured by the percentages of subjects with hSBA titers ≥LLQ, ≥5, ≥8, ≥16, ≥32, ≥64, ≥128 against M07-0241084 B strain was assessed. | At Month 0, Month 2, Month 3, Month 7 and Month 13. | 
| Percentages of Subjects With hSBA Titers ≥LLQ, ≥5, ≥8, ≥16, ≥32, ≥64, ≥128 Against 96217 B Strain for All Schedules. | The kinetic of immune response (at Months 0, 2, 3, 7 and 13) following different vaccination schedules as measured by the percentages of subjects with hSBA titers ≥LLQ, ≥5, ≥8, ≥16, ≥32, ≥64, ≥128 against 96217 B strain was assessed. | At Month 0, Month 2, Month 3, Month 7 and Month 13. | 
| Percentages of Subjects With hSBA Titers ≥LLQ, ≥5, ≥8, ≥16, ≥32, ≥64, ≥128 Against A Human Serogroup for All Schedules. | The kinetic of immune response (at Months 0, 2, 3, 7 and 13) following different vaccination schedules as measured by the percentages of subjects with hSBA titers ≥LLQ, ≥5, ≥8, ≥16, ≥32, ≥64, ≥128 against A human serogroup was assessed. | At Month 0, Month 2, Month 3, Month 7 and Month 13. | 
| Percentages of Subjects With hSBA Titers ≥LLQ, ≥5, ≥8, ≥16, ≥32, ≥64, ≥128 Against C Human Serogroup for All Schedules. | The kinetic of immune response (at Months 0, 2, 3, 7 and 13) following different vaccination schedules as measured by the percentages of subjects with hSBA titers ≥LLQ, ≥5, ≥8, ≥16, ≥32, ≥64, ≥128 against C human serogroup was assessed. | At Month 0, Month 2, Month 3, Month 7 and Month 13. | 
| Percentages of Subjects With hSBA Titers ≥LLQ, ≥5, ≥8, ≥16, ≥32, ≥64, ≥128 Against W Human Serogroup for All Schedules. | The kinetic of immune response (at Months 0, 2, 3, 7 and 13) following different vaccination schedules as measured by the percentages of subjects with hSBA titers ≥LLQ, ≥5, ≥8, ≥16, ≥32, ≥64, ≥128 against W human serogroup was assessed. | At Month 0, Month 2, Month 3, Month 7 and Month 13. | 
| Percentages of Subjects With hSBA Titers ≥LLQ, ≥5, ≥8, ≥16, ≥32, ≥64, ≥128 Against Y Human Serogroup for All Schedules. | The kinetic of immune response (at Months 0, 2, 3, 7 and 13) following different vaccination schedules as measured by the percentages of subjects with hSBA titers ≥LLQ, ≥5, ≥8, ≥16, ≥32, ≥64, ≥128 against Y human serogroup was assessed. | At Month 0, Month 2, Month 3, Month 7 and Month 13. | 
| Percentages of Subjects With Two-, Three- and Four-fold Titer Rise Against Serogroups A, C, W and Y and Serogroup B Test Strains for All Schedules. | The kinetic of immune response (at Months 2, 3, 7 and 13) following different vaccination schedules as measured by the percentages of subjects with two-, three- and four-fold titer rise against serogroups A, C, W and Y and serogroup B test strains was assessed. The two/three/four fold titer rise is defined as: a) for subjects with prevaccination hSBA titers ≤ LLQ, a postvaccination hSBA ≥ 2/3/4 LLQ; b) for subjects with a prevaccination hSBA titers ≥ LLQ, an increase of at least 2/3/4 times of the prevaccination hSBA titer. | At Month 2, Month 3, Month 7 and Month 13 | 
| The Area Under the Curve (AUC) for Percentage of Subjects With hSBA Titers ≥LLQ for All Serogroups and Strains. | The area under the curve for percentage of subjects with hSBA titers ≥ LLQ for all serogroups (A, C, W and Y) and for all serogroup B test strains (M14459, 96217, NZ98/254 and M07-0241084) was summarized overall (from Month 0 to Month 13) and by period (from Month 0 to Month 2, Month 2 to Month 3, Month 3 to Month 7 and Month 7 to Month 13) by vaccine groups. It was computed as the sum of the trapezoidal areas and the time unit used was the month. AUC 0_13 = (r0+r2)(2-0)/2 + (r2+r3)(3-2)/2 + (r3+r7)(7-3)/2 + (r7+r13)(13-7)/2 with ri = percentages of subjects with both hSBA titers >= LLQ against N. meningitis for all serogroups A, C, W and Y and for all serogroup B test strains at Month 1. | From Month 0 to Month 13 | 
| Number of Participants Reporting Any Solicited Local or Systemic AEs and Other Indicators of Reactogenicity Within 30 Minutes After Vaccination. | Number of participants reporting any solicited local or systemic AEs and other indicators of reactogenicity within 30 minutes after each vaccination. Assessed solicited symptoms were Pain, erythema and induration. Assessed solicited systemic symptoms were Fatigue, headache, myalgia, arthralgia, loss of appetite, nausea, chills, and fever (body temperature ≥38.0°C). | Within 30 minutes after vaccination | 
| Number of Participants Reporting Any Unsolicited AEs Within 30 Minutes After Vaccination. | An unsolicited adverse event is an adverse event that was not solicited and that was spontaneously communicated by a participant and/or parent/legal guardian who has signed the informed consent. Number of participants reporting any unsolicited AE within 30 minutes after each vaccination. | Within 30 minutes after vaccination | 
| Number of Participants Reporting Unsolicited AEs From Day 1 to Day 30 After Any Vaccination. | The number of participants reporting unsolicited AEs and possibly or probably related unsolicited AEs were assessed. | Day 1 through Day 30 after any vaccination | 
| Number of Participants Reporting Any Solicited Local or Systemic Adverse Events (AEs) and Other Indicators of Reactogenicity From Day 1 to Day 7. | Number of participants reporting any solicited local or systemic AEs and other indicators of reactogenicity from Day 1 (6 hours) to Day 7 after any meningococcal vaccination is reported. | At Day 1 (6 hours) to Day 7 after vaccination | 
| Number of Participants Reporting Any Serious AE (SAE), Medically Attended AEs (MAAEs), AEs Leading to Premature Withdrawal | The number of participants reporting any SAE, possibly or probably related SAE(s), medically-attended AEs, AEs leading to premature withdrawal, AEs leading to death, AEs leading to hospitalization and AEs leading to dose reduction, interruption and delay in study vaccination during the entire study period is reported. | During the entire study period (Month 0 to Month 13) |