A Study to Evaluate 4-year Antibody Persistence and Booster Response Following MenABCWY Vaccination in Healthy Adolescents and Young Adults Who Previously Participated in Studies V102_02 (NCT01210885) and V102_02E1 (NCT01367158)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate persistence of bactericidal antibodies for N. meningitidis serogroups A, C, W, and Y and serogroup B test strains approximately 4 years after primary vaccination in subjects who previously received a 2-dose series of MenABCWY+Outer membrane Vesicles (OMV) or a single dose of MenACWY, to evaluate immune response against N. meningitidis serogroups A, C, W and Y and serogroup B test strains 30 days after a dose of MenABCWY+OMV in previously vaccinated subjects, and 30 days after a 2-dose series in vaccine-naive subjects of similar age, to evaluate kinetics of immune response at 3, 7, and 30 days after a booster dose of MenABCWY+OMV in previously vaccinated subjects and to explore differences in the kinetics of immune response 3, 7 and 30 days after an accelerated 2 dose series of MenABCWY+OMV separated by 30 days given to vaccine-naive subjects, and to assess immunogenicity of 2 doses of MenABCWY+OMV at Day 61 in vaccine-naive subjects and subjects who previously received one dose of MenACWY

Detailed Description
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Subjects will be randomised into two different blood draw schedules according to a 1:1 ratio

Official Title
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A Phase 2, Open-label, Controlled, Multi-center Extension Study to Evaluate 4-year Antibody Persistence and Booster Response Following MenABCWY Vaccination in Healthy Adolescents and Young Adults Who Previously Participated in Studies V102_02 (NCT01210885) and V102_02E1 (NCT01367158)

Conditions
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Meningococcal Disease, Infections, Meningococcal

Intervention / Treatment
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* Biological: MenABCWY+OMV vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals who received either 2 doses of MenABCWY+OMV or a single dose of MenACWY followed by a dose of placebo, with the last study vaccine given approximately 48 to 56 months before study V102_02E2 (NCT01367158), who received Tdap only in V102_02E1 (NCT01367158) study and who received no other meningococcal vaccines; Or A proportional number of subjects in each site aged 15 through 23 years on the day of informed consent/assent who did not participate in the V102_02 (NCT01210885) study and have not previously received any meningococcal vaccine. Individuals who / whose parent(s)/legal guardian(s) have voluntarily given written informed consent/assent after the nature of the study has been explained according to local regulatory requirements, prior to study entry. Individuals who can comply with study procedures including blood draws and follow-up. Males Or Females of non-childbearing potential Or Females of childbearing potential who are not pregnant or breastfeeding and who are using an effective birth control method which they have used for at least 30 days prior to study entry, and which they intend to use for at least 30 days after the last study vaccination Exclusion Criteria: History of any meningococcal vaccine administration (study group C) or History of any meningococcal vaccine administration other than vaccination given in the parent V102_02 (NCT01210885) study (study groups A and B). Progressive, unstable or uncontrolled clinical conditions. Hypersensitivity, including allergy, to any component of vac-cines (including diphtheria toxoid (CRM197) and latex) whose use is foreseen in this study. Clinical conditions representing a contraindication to intra-muscular vaccination and blood draws. Abnormal function of the immune system resulting from: a.Clinical conditions. Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days within 90 days prior to enrollment. Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to informed consent. Received immunoglobulins or any blood products within 90 days prior to enrollment. Received an investigational or non-registered medicinal product within 30 days prior to enrollment. Received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrolment in this study or who are planning to receive any vaccine within 14 days from the study vaccines. Study personnel as an immediate family or household member. Who have experienced a moderate or severe acute infection and/or fever (defined as temperature 38°C) within 3 days prior to enrollment. Who have received systemic antibiotic treatment within 3 days prior to enrollment. Any other clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study.

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 23 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: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MenABCWY+OMV Group<br>Subjects who received 2 doses of MenABCWY+OMV vaccine in the parent study V102_02 (NCT01210885) and received no subsequent meningococcal vaccines, received a booster dose of MenABCWY+OMV vaccine in the current study at Day 1. | Biological: MenABCWY+OMV vaccine<br>* Intramuscular injection of a single dose at Day 1 to subjects in the MenABCWY+OMV Group or as a 2 doses at Day 1 and Day 31, one month apart, to subjects in the MenACWY and Naive Groups.<br>|
| Experimental: MenACWY Group<br>Subjects who received MenACWY vaccine in the parent study V102_02 (NCT01210885) and received no subsequent meningococcal vaccines, received 2 doses of MenABCWY+OMV vaccine, one month apart (Day 1 and Day 31), in the current study. | Biological: MenABCWY+OMV vaccine<br>* Intramuscular injection of a single dose at Day 1 to subjects in the MenABCWY+OMV Group or as a 2 doses at Day 1 and Day 31, one month apart, to subjects in the MenACWY and Naive Groups.<br>|
| Experimental: Naive Group<br>Subjects similar in age to subjects in the MenABCWY+OMV and MenACWY groups, who had not previously received any meningococcal vaccine and who received 2 doses of MenABCWY+OMV vaccine, 1 month apart (Day 1 and Day 31), in the current study. | Biological: MenABCWY+OMV vaccine<br>* Intramuscular injection of a single dose at Day 1 to subjects in the MenABCWY+OMV Group or as a 2 doses at Day 1 and Day 31, one month apart, to subjects in the MenACWY and Naive Groups.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects With hSBA ≥ Lower Limit Quantitation (LLQ) Against N. Meningitidis Serogroups A, C, W and Y and Serogroup B Test Strains. | The HT-hSBA assay format was changed in 2015 in response to CBER comments and no new LLQ values were defined as the validation of this format was not relevant. The LLQ cut off values for the old assay format correspond to 8 for serogroups A,C,W and Y and 5 for serogroup B strains and these results are presented in outcome measures 2 and 3 and are considered final in Company's judgement. | At Day 1 (4 years persistence) | 
| Percentages of Subjects With hSBA ≥ 8 Against N. Meningitidis Serogroups A, C, W and Y. | Antibody levels against N. meningitidis serogroups A, C, W and Y in subjects who previously received MenABCWY+OMV or MenACWY approximately 4 years earlier, and in Naïve subjects as measured by the percentages of subjects with hSBA ≥ 8. | At Day 1 (4 years persistence) | 
| Percentages of Subjects With hSBA ≥ 5 Against N. Meningitidis Serogroup B Test Strains. | Antibody levels against N. meningitidis serogroup B test strains in subjects who previously received MenABCWY+OMV or MenACWY approximately 4 years earlier, and in Naïve subjects as measured by the percentages of Subjects with hSBA ≥ 5. The Meningococcal B Strains were M14459, M01-0240364, NZ98/254, M10713, H44/76 and 5/99. | At Day 1 (4 years persistence) | 
| Geometric Mean hSBA Titers (GMTs) Against N. Meningitidis Serogroups A, C, W and Y and Serogroup B Test Strains. | GMTs against N. meningitidis serogroups A, C, W and Y and serogroup B test strains in subjects who previously received MenABCWY+OMV or MenACWY approximately 4 years earlier, and in Naïve subjects. The Meningococcal B Strains were M14459, M01-0240364, NZ98/254, M10713, H44/76 and 5/99. | At Day 1 | 
| Percentages of Subjects With hSBA ≥ LLQ Against N. Meningitidis Serogroups A, C, W and Y and B Test Strains. | The HT-hSBA assay format was changed in 2015 in response to CBER comments and no new LLQ values were defined as the validation of this format was not relevant. The LLQ cut off values for the old assay format correspond to 8 for serogroups A,C,W and Y and 5 for serogroup B strains and these results are presented in outcome measures 6 and 7 and are considered final in Company's judgement. | At Day 31 | 
| Percentages of Subjects With hSBA ≥ 8 Against N. Meningitidis Serogroups A, C, W and Y. | Immune response against N. meningitidis serogroups A, C, W and Y 30 days after a single dose of MenABCWY+OMV in subjects who previously vaccinated subjects, and in Naïve subjects of similar age, as measured by the percentages of subjects with hSBA ≥ 8. | At Day 31 | 
| Percentages of Subjects With hSBA ≥ 5 Against N. Meningitidis Serogroup B Test Strains. | Immune response against N. meningitidis serogroup B test strains 30 days after a single dose of MenABCWY+OMV in previously vaccinated subjects, and in Naïve subjects of similar age, as measured by the percentages of Subjects with hSBA ≥ 5. The Meningococcal B Strains were M14459, M01-0240364, NZ98/254, M10713, H44/76 and 5/99. | At Day 31 | 
| Geometric Mean hSBA Titers (GMTs) Against N. Meningitidis Serogroups A, C, W and Y and Serogroup B Test Strains. | GMTs against N. meningitidis serogroups A, C, W and Y and serogroup B test strains 30 days after a single dose of MenABCWY+OMV in previously vaccinated subjects, and in Naïve subjects of similar age. The Meningococcal B Strains were M14459, M01-0240364, NZ98/254, M10713, H44/76 and 5/99. | At Day 31 | 
| Geometric Mean hSBA Ratio (GMRs) Against N. Meningitidis Serogroups A, C, W and Y and Serogroup B Test Strains. | GMRs as measure of the immune response against N. meningitidis serogroups A, C, W and Y and serogroup B test strains in previously vaccinated subjects, and in Naïve subjects of similar age. The Meningococcal B Strains were M14459, M01-0240364, NZ98/254, M10713, H44/76 and 5/99. | Day 31 versus Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects With hSBA ≥ LLQ Against N. Meningitidis Serogroups A, C, W and Y and Serogroup B Test Strains. | The HT-hSBA assay format was changed in 2015 in response to CBER comments and no new LLQ values were defined as the validation of this format was not relevant. The LLQ cut off values for the old assay format correspond to 8 for serogroups A,C,W and Y and 5 for serogroup B strains and these results are presented in outcome measures 12 and 13 and are considered final in Company's judgement. | At Days 1, 4, 8 and 31 | 
| Percentages of Subjects With hSBA ≥ LLQ Against N. Meningitidis Serogroups A, C, W and Y and Serogroup B Test Strains. | The HT-hSBA assay format was changed in 2015 in response to CBER comments and no new LLQ values were defined as the validation of this format was not relevant. The LLQ cut off values for the old assay format correspond to 8 for serogroups A,C,W and Y and 5 for serogroup B strains and these results are presented in outcome measures 12 and 13 and are considered final in Company's judgement. | At Days 1, 31, 34, 38 and 61 | 
| Percentages of Subjects With hSBA ≥ 8 Against N. Meningitidis Serogroups A, C, W and Y. | Kinetics of immune response following 1 dose of MenABCWY+OMV in subjects who previously received 2 doses of MenABCWY+OMV or 1 dose of MenACWY, at Days 1, 4, 8, 31, 34, 38 and 61, as measured by the percentages of subjects with hSBA ≥ 8. | At Days 1, 4, 8, 31, 34, 38 and 61 | 
| Percentages of Subjects With hSBA ≥ 5 Against N. Meningitidis Serogroup B Test Strains. | Kinetics of immune response against N. meningitidis serogroup B test strains in previously vaccinated subjects, at Days 1, 4, 8, 31, 34, 38 and 61, as measured by the percentages of Subjects with hSBA ≥ 5. The Meningococcal B Strains were M14459, M01-0240364, NZ98/254, M10713, H44/76 and 5/99. | At Days 1, 4, 8, 31, 34, 38 and 61 | 
| Geometric Mean hSBA Titers (GMTs) Against N. Meningitidis Serogroups A, C, W and Y and Serogroup B Test Strains. | GMTs at Day 1, 4, 8, 31 as measure of the kinetics of the immune response following a dose of MenABCWY+OMV, in subjects who previously received 2 doses of MenABCWY+OMV or 1 dose of MenACWY. This outcome measure reports data only for the MenABCWY+OMV and MenACWY Groups as per protocol. The Meningococcal B Strains were M14459, M01-0240364, NZ98/254, M10713, H44/76 and 5/99. | At Days 1, 4, 8 and 31. | 
| Geometric Mean hSBA Titers (GMTs) Against N. Meningitidis Serogroups A, C, W and Y and Serogroup B Test Strains. | GMTs at Day 1, 31, 34, 38, 61 as measure of the kinetics of the immune response following a dose of MenABCWY+OMV, in subjects who were not primed with any meningococcal vaccine (i.e., Naïve Group). This outcome measure reports data for only the Naïve Group as per protocol. The Meningococcal B Strains were M14459, M01-0240364, NZ98/254, M10713, H44/76 and 5/99. | At Days 1, 31, 34, 38 and 61 | 
| GMR Against N. Meningitidis Serogroups A, C, W and Y and Serogroup B Test Strains. | GMRs as measure of the kinetics of the immune response following a dose of MenABCWY+OMV, in subjects who previously received 2 doses of MenABCWY+OMV or 1 dose of MenACWY. The Meningococcal B Strains were M14459, M01-0240364, NZ98/254, M10713, H44/76 and 5/99. | At Days 4, 8 and 31 versus Day 1. | 
| GMR Against N. Meningitidis Serogroups A, C, W and Y and Serogroup B Test Strains. | GMRs as measure of the kinetics of the immune response following a dose of MenABCWY+OMV, in Naïve subjects. The Meningococcal B Strains were M14459, M01-0240364, NZ98/254, M10713, H44/76 and 5/99. | At Days 31, 34, 38 and 61 versus Day 1. | 
| Percentages of Subjects With hSBA ≥ LLQ Against N. Meningitidis Serogroups A, C, W and Y and Serogroup B Test Strains. | The HT-hSBA assay format was changed in 2015 in response to CBER comments and no new LLQ values were defined as the validation of this format was not relevant. The LLQ cut off values for the old assay format correspond to 8 for serogroups A,C,W and Y and 5 for serogroup B strains and these results are presented in outcome measures 19 and 20 and are considered final in Company's judgement. | At Day 61 | 
| Percentages of Subjects With hSBA ≥ 8 Against N. Meningitidis Serogroups A, C, W and Y. | Immunogenicity against N. meningitidis serogroup A, C, W and Y following 2 doses of MenABCWY+OMV in subjects who previously received 1 dose of MenACWY and Naïve subjects, at Day 61, as measured by percentages of subjects with hSBA ≥ 8. | At Day 61 | 
| Percentages of Subjects With hSBA ≥ 5 Against N. Meningitidis Serogroup B Test Strains. | Immunogenicity against N. meningitidis serogroup B test strains following 2 doses of MenABCWY+OMV in subjects who previously received 1 dose of MenACWY and Naïve subjects, at Day 61, as measured by percentages of subjects with hSBA ≥ 5. The Meningococcal B Strains were M14459, M01-0240364, NZ98/254, M10713, H44/76 and 5/99. | At Day 61 | 
| GMTs Against N. Meningitidis Serogroups A, C, W and Y and Serogroup B Test Strains. | GMTs as measure of the immunogenicity of 2 doses of MenABCWY+OMV in subjects who previously received 1 dose of MenACWY and Naïve subjects, at Day 61. The Meningococcal B Strains were M14459, M01-0240364, NZ98/254, M10713, H44/76 and 5/99. | At Day 61 | 
| GMRs Against N. Meningitidis Serogroups A, C, W and Y and Serogroup B Test Strains. | GMRs as measure of the immunogenicity of 2 doses of MenABCWY+OMV in subjects who previously received 1 dose of MenACWY and Naïve subjects. The Meningococcal B Strains were M14459, M01-0240364, NZ98/254, M10713, H44/76 and 5/99. | Day 61 versus Day 1 (baseline) | 
| Number of Subjects Reporting Any Unsolicited and Solicited Adverse Events (AEs) Within 30 Min After Each Vaccination | Any solicited and unsolicited AEs reported within 30 minutes after each vaccination. Assessed solicited local symptoms were: Erythema and Induration. Any = occurrence of the symptom spreading beyond 25 millimeters (mm) of injection site. Assessed solicited general symptoms were: Arthralgia, Chills, Fatigue, Headache, Loss of Appetite, Myalgia, Nausea and Fever (body temperature ≥ 38°C). Other solicited data included: Prevention of Pain and/or Fever and Treatment of Pain and/or Fever. Any = occurrence of the symptom regardless of intensity grade. Note: There were no unsolicited AEs reported within 30 minutes after vaccination. | Within 30 min after each vaccination | 
| Number of Subjects With Any Solicited Local Symptoms | Assessed solicited local symptoms were Erythema, Induration and Pain. Any = occurrence of the symptom spreading beyond 25 millimeters (mm) of injection site. | From Day 1 (6 hours) to Day 7 after each vaccination | 
| Number of Subjects With Solicited Systemic Symptoms and Other Solicited Data | Assessed solicited systemic symptoms were Arthralgia, Chills, Fatigue, Headache, Loss of Appetite, Myalgia, Nausea and Fever (body temperature ≥ 38°C). Other solicited data included: Prevention of pain and/or fever and Treatment of pain and/or fever. Any = occurrence of the symptom regardless of intensity grade. | From Day 1 (6 hours) to Day 7 after each vaccination | 
| Number of Subjects With Unsolicited Adverse Events (AEs). | 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. Possibly or Probably related = AE assessed by the investigator as related to the vaccination. | From Day 1 to Day 31 after each vaccination (Day 1 to Day 31 for MenABCWY+OMV Group and Day 1 to Day 61 for MenACWY and Naive Groups) | 
| Number of Subjects With Medically Attended AEs Reported During the Entire Study Period. | Medically attended AEs = 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 medically attended AE(s) = Occurrence of any medically attended AE(s) regardless of intensity grade or relation to vaccination. | During the entire study period (Day 1 to Day 31 for MenABCWY+OMV Group and Day 1 to Day 61 for MenACWY and Naive Groups) | 
| Number of Subjects With Unsolicited AEs Leading to Premature Withdrawal From Study Reported During the Entire Study Period. | The number of subjects who reported unsolicited AEs leading to premature withdrawal from study after any vaccination. | From Day 1 to Day 31 (MenABCWY+OMV Group) and from Day 1 to Day 61 (MenACWY and Naive Groups) | 
| Number of Subjects With Serious Adverse Events (SAEs) Reported During the Entire Study Period. | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Any SAE(s) = Occurrence of any SAE(s) regardless of intensity grade or relation to vaccination. Possibly or probably related SAE(s) = SAE(s) assessed by the investigator as related to the vaccination. | During the entire study period (Day 1 to Day 31 for MenABCWY+OMV Group and Day 1 to Day 61 for MenACWY and Naive Groups) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibody persistence, Young Adults, Healthy Adolescents, MenABCWY vaccine, Booster response, MenABCWY+OMV