Study to Assess the Safety and Immunogenicity of a Single Dose of GlaxoSmithKline's (GSK) Meningococcal MenACWY-CRM Vaccine (Menveo), Administered to Subjects 15 Through 55 Years of Age, Approximately 4-6 Years After Primary ACWY Vaccination

Study Overview
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Brief Summary
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The purpose/aim of this study is to assess the safety and antibody response to vaccination with a booster dose of Menveo given 4-6 years after primary MenACWY vaccination and to assess the safety and antibody response to a single dose of Menveo given to vaccine-naïve subjects

Detailed Description
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This is a phase 3b, controlled, open-label, multi-center study to evaluate safety and immunogenicity of Menveo after a single vaccination in healthy individuals who were vaccinated with Menveo or Menactra 4 to 6 years before and in vaccine-naive individuals. Vaccine-naive subjects: subjects who have not received any meningococcal vaccine prior to participation to this clinical trial. Subjects will be randomised into one of the two different blood draw schedules according to a 1:1 ratio. Blood draws at Day 1, Day 4 and Day 29 Blood draws at Day 1, Day 6 and Day 29

Official Title
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A Phase 3b, Controlled, Open-Label, Multi-Center Study to Evaluate Safety and Immunogenicity of a Single Dose of GlaxoSmithKline's Meningococcal ACWY Conjugate Vaccine (Menveo), Administered to Healthy Individuals 15 Through 55 Years of Age, Approximately 4-6 Years After Primary ACWY Vaccination

Conditions
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Infections, Meningococcal

Intervention / Treatment
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* Biological: Meningococcal (groups A, C, W and Y) oligosaccharide diphtheria CRM-197 conjugate Vaccine (Menveo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals of 15 through 55 years of age on the day of informed consent or assent. Individuals who received Menveo 4 to 6 years prior to enrolment at an age of 11 years or older OR Individuals who received Menactra 4 to 6 years prior to enrolment at an age of 11 years or older OR Individuals who have not received any previous meningococcal vaccine. Individuals who have voluntarily given written informed consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry. If the subject is under age 18 at the time of enrolment, the parent(s)/legal guardian(s) of the subject should have voluntarily given written informed consent. Individuals who can comply with study procedures including follow-up. Males Or Females of non-childbearing potential Or Females of childbearing potential who are using an effective birth control method which they intend to use for at least 30 days after the study vaccination. Exclusion Criteria: Each subject must not have: History of any meningococcal vaccine administration other than the single vaccination given 4 to 6 years before OR History of any meningococcal vaccine administration. Current or previous, confirmed or suspected disease caused by N. meningitidis. Household contact with and/or intimate exposure to an individual with any laboratory confirmed N. meningitidis infection within 60 days prior to study vaccination. Progressive, unstable or uncontrolled clinical conditions. Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study. Clinical conditions representing a contraindication to intramuscular vaccination (IM) and blood draws. Abnormal function of the immune system resulting from: Clinical conditions. Systemic administration of corticosteroids for more than 14 consecutive days within 90 days prior to study vaccination. Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to study vaccination. Received immunoglobulins or any blood products within 180 days prior to informed consent. Received systemic antibiotic treatment within 3 days prior to study vaccination or blood draw. Received an investigational or non-registered medicinal product within 30 days prior to study vaccination. Study personnel as an immediate family or household member. Individuals who have received any other vaccines within 7 days or 14 days prior to vaccination in this study or who are planning to receive any vaccine within 28 days from the study vaccination. Individuals who have experienced a moderate or severe acute infection and/or fever defined as a temperature ≥38°C (100.4°F) within 3 days prior to study vaccination. Any other clinical condition that, in the opinion of the investigator, might 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: 55 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: Menveo-Menveo Group<br>Approximately 300 subjects, who were vaccinated with a single dose of Menveo 4 to 6 years before, will receive one dose of MenACWY-CRM at Day 1. | Biological: Meningococcal (groups A, C, W and Y) oligosaccharide diphtheria CRM-197 conjugate Vaccine (Menveo)<br>* One intramuscular injection of MenACWY at Day 1.<br>|
| Experimental: Menactra-Menveo Group<br>Approximately 300 subjects, who were vaccinated with a single dose of Menactra 4 to 6 years before, will receive one dose of MenACWY-CRM at Day 1. | Biological: Meningococcal (groups A, C, W and Y) oligosaccharide diphtheria CRM-197 conjugate Vaccine (Menveo)<br>* One intramuscular injection of MenACWY at Day 1.<br>|
| Active Comparator: Naive Group<br>Aproximately 100 subjects, of similar age to subjects enrolled in other primed groups, who have not received any meningococcal vaccination, will receive one dose of MenACWY-CRM at Day 1. | Biological: Meningococcal (groups A, C, W and Y) oligosaccharide diphtheria CRM-197 conjugate Vaccine (Menveo)<br>* One intramuscular injection of MenACWY at Day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects With Human Serum Bactericidal Antibody (hSBA) Seroresponse Against Neisseria Meningitidis Serogroups A, C, W and Y. | Seroresponse was defined as follows:for subjects with pre-vaccination hSBA titers< 4,postvaccination hSBA titers≥16;for subjects with pre-vaccination hSBA titers≥4,post vaccination hSBA titers of atleast 4 times the pre-vaccination titers.Criteria to demonstrate primary objectives:Immune response sufficiency was tested sequentially;first in the group of subjects who received primary vaccination with Menveo &,if met,also in group of subjects who received primary vaccination with Menactra.Immune response is considered sufficient if lower limit of the 1-sided 97.5% CI for percentage of subjects with hSBA seroresponse against serogroups A, C, W & Y is greater than 75%.Study is considered successful if immune response sufficiency is demonstrated atleast in group of subjects who received primary vaccination with Menveo.This outcome measure was assessed only on subjects from Menveo-Menveo & Menactra-Menveo groups.Data from pooled and Naive groups are presented as part of secondary objectives | At Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Any Unsolicited Adverse Events (AEs) | An AE can be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom , or disease temporally associated with the use of an investigational product, whether or not considered related to the investigational product. An unsolicited adverse event is an adverse event that was not solicited using a subject diary and that was spontaneously communicated by a subject and/or parent(s)/legal guardian(s) who has signed the informed consent. | Within 30 minutes after vaccination | 
| Number of Subjects Reporting Solicited Local and Systemic AEs | Assessed solicited local symptoms were injection site pain, erythema, induration. Assessed solicited systemic symptoms were fatigue, headache, myalgia, arthralgia, loss of appetite, nausea, chills and fever [defined and measured by a body temperature ≥37.5 degrees Celsius (ºC)]. Threshold for Erythema and Induration: Grade 0 (<25 mm), Any (>= 25 mm) | From Day 1 (6 hours) through Day 7 after vaccination | 
| Number of Subjects Reporting Other Indicators of Reactogenicity | Assessed indicators of reactogenicity were use of analgesics/antipyretics for prophylaxis, use of analgesics/antipyretics for treatment, body temperature (described as 0.5 °C increments from ≥ 36.0ºC) | From Day 1 (6 hours) through Day 7 after vaccination | 
| Number of Subjects Reporting All Unsolicited AEs | An AE can be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom , or disease temporally associated with the use of an investigational product, whether or not considered related to the investigational product. An unsolicited adverse event was an adverse event that was not solicited using a subject diary and that was spontaneously communicated by a subject and/or parent(s)/legal guardian(s) who has signed the informed consent. | From Day 1 through Day 29 after vaccination | 
| Number of Subjects Reporting Medically-attended AEs (MAAEs), AEs Leading to Withdrawal and Serious AEs (SAEs) | Medically attended AEs were defined as symptoms or illnesses requiring hospitalization, or emergency room visit, or visit to/by a health care provider. SAE was defined as any untoward medical occurrence that at any dose resulted in: death, was life-threatening, required or prolonged hospitalization, persistent or significant disability/incapacity, congenital anomaly/or birth defect, an important and significant medical event that might not have been immediately life threatening or resulting in death or hospitalization but, based upon appropriate medical judgment, might jeopardized the subject or might required intervention to prevent one of the other outcomes listed. | From Day 1 through Day 181 (entire study period) | 
| Percentages of Subjects With hSBA Titer ≥8 Against N. Meningitidis Serogroup A | For each study group and in the pooled group, percentages of subjects with hSBA titer ≥8 and associated two-sided 95%CIs were calculated. | At Day 1 (pre-vaccination), Day 4, Day 6 and Day 29 | 
| Percentages of Subjects With hSBA Titer ≥8 Against N. Meningitidis Serogroup C | For each study group and in the pooled group, percentages of subjects with hSBA titer ≥8 and associated two-sided 95%CIs were calculated. | At day 1(pre-vaccination) , day 4, day 6 and day 29 | 
| Percentage of Subjects With hSBA Titer ≥8 Against N. Meningitidis Serogroup W | For each study group and in the pooled group, percentages of subjects with hSBA titer ≥8 and associated two-sided 95%CIs were calculated. | At day 1(pre-vaccination), day 4, day 6 and day 29 | 
| Percentages of Subjects With hSBA Titer ≥8 Against N. Meningitidis Serogroup Y | For each study group and in the pooled group, percentages of subjects with hSBA titer ≥8 and associated two-sided 95%CIs were calculated. | At day 1(pre-vaccination), day 4, day 6 and day 29 | 
| Percentages of Subjects With hSBA Titer ≥16 Against N. Meningitidis Serogroup A | For each study group and in the pooled group, percentages of subjects with hSBA titer ≥16 and associated two-sided 95%CIs were calculated. | At day 1(pre-vaccination), day 4, day 6 and day 29 | 
| Percentages of Subjects With hSBA Titer ≥16 Against N. Meningitidis Serogroup C | Analysis was performed on per protocol set for immunogenicity, which included all randomized subjects who had no protocol deviations and were not excluded due to other reasons defined prior to unblinding/analysis, who received study vaccination and provided evaluable serum samples at each time point, with result available for at least 1 serogroup | At day 1(pre-vaccination) , day 4, day 6 and day 29 | 
| Percentages of Subjects With hSBA Titer ≥16 Against N. Meningitidis Serogroup W | For each study group and in the pooled group, percentages of subjects with hSBA titer ≥16 and associated two-sided 95%CIs were calculated. | At day 1(pre-vaccination), day 4, day 6 and day 29 | 
| Percentages of Subjects With hSBA Titer ≥16 Against N. Meningitidis Serogroup Y | For each study group and in the pooled group, percentages of subjects with hSBA titer ≥16 and associated two-sided 95%CIs were calculated. | At day 1(pre-vaccination) , day 4, day 6 and day 29 | 
| Percentages of Subjects With hSBA Seroresponse Against N. Meningitidis Serogroups A, C, W and Y | Seroresponse is defined for this study as follows: For subjects with pre-vaccination titers <4, postvaccination titers ≥ 16; for subjects with pre-vaccination titers ≥4, post vaccination titers at least 4 times the pre-vaccination titers. | At Day 4 and Day 6 | 
| hSBA Geometric Mean Titers (GMTs) Against N. Meningitidis Serogroup A, C, W and Y. | For each N. meningitidis serogroup A, C, W and Y, unadjusted GMTs were calculated, with their associated two-sided 95% Confidence Interval. | At Day 1 (pre-vaccination), Day 4, Day 6 and Day 29 | 
| Within Group hSBA Geometric Mean Ratios (GMRs) | Within each study group and for each serogroup, GMRs were calculated,at: Visit Day 4 versus at Visit Day 1; Visit Day 6 versus at Visit Day 1; and Visit Day 29 versus at Visit Day 1. The unadjusted GMRs and 95% CIs are constructed by exponentiating the mean within-group differences in log-transformed titers and the corresponding 95% CIs. | At Day 4, Day 6, Day 29 compared to Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Booster vaccination, Meningitis, Antibody persistence, Meningococcal disease