South Australian Meningococcal B Vaccine Herd Immunity Study

Study Overview
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Brief Summary
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To estimate the effect on carriage, all year 10, 11, and 12 students will be offered 4CMenB vaccination in South Australia through schools over the study period with 50% of the students enrolled receiving the vaccine in 2017 and 50% in 2018. In year 10 and 11 students, posterior pharyngeal swabs will be obtained at baseline and 12 months post baseline to estimate the difference in carriage prevalence of all genogroups of N. meningitidis between vaccinated and unvaccinated participants.

Detailed Description
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This cluster randomised controlled study will be conducted in the context of funded 4CMenB vaccine offered to all students in years 10, 11, and 12. Year 10 and 11 students will undergo baseline and 12 months posterior pharyngeal swabs. Year 12 students will undergo baseline posterior pharyngeal swabs only. Randomisation will take place at the school level and will be stratified by school size ((<60, 60 to 119, and ≥120 students per year level) and school socio-economic status (SES), as measured by the Index of Community Socio-Educational Advantage (ICSEA); (ICSEA <970, 970 to 1020, >1020) For the purposes of the study a school is defined as an educational institution at which students in years 10, 11, 12 physically attend school during the week. All 260 schools in metropolitan and rural SA will be approached to participate in the study. All schools agreeing to participate will be randomised to 4CMenB vaccine in 2017 or 2018. Students at schools randomised to receive the vaccine at baseline will receive the 4CMenB vaccine in 2017. Students at schools randomised to receive the vaccine at the 12 month posterior pharyngeal swab will receive the 4CMenB vaccine in 2018. Primary Objectives • Estimate the difference in carriage prevalence of disease causing genogroup of N. meningitidis (A, B, C, W, X, Y) following the 12 month pharyngeal swab in year 10 and 11 students who received two doses of Bexsero®, compared to unvaccinated students. Secondary objectives Estimate the difference in carriage prevalence of each disease causing genogroup of N. meningitidis (A, B, C, W, X, Y) following the 12 month pharyngeal swab in year 10 and 11 students who received two doses of Bexsero®, compared to unvaccinated students. Estimate the difference in carriage prevalence of all genogroups of N. meningitidis following the 12 month pharyngeal swab in year 10 and 11 students who received two doses of Bexsero ®, compared to unvaccinated students. Estimate the difference in acquisition (negative at baseline, positive at 12 month followup) of carriage of disease causing genogroups of N. meningitidis (A, B, C, W, X, Y) over a 12 month period in students who received two doses of Bexsero ®, compared to unvaccinated students. Estimate the difference in acquisition (negative at baseline, positive at 12 month followup) of carriage of all genogroups of N. meningitidis over a 12 month period in students who received two doses of Bexsero ®, compared to unvaccinated students Identify characteristics associated with carriage prevalence of all genogroups N. meningitidis in South Australian school students at baseline and 12 months. Identify characteristics associated with carriage prevalence of disease causing genogroups of N. meningitidis (A, B, C, W, X, Y) in South Australian school students at baseline and 12 months. Exploratory objectives Describe changes in invasive meningococcal rates (attack rates) across all age groups pre and post 4CMenB vaccine intervention in South Australia. Describe N. meningitidis carriage density in year 10, 11, and 12 students using qPCR at baseline and 12 months in both vaccinated and unvaccinated students. Describe genome sequencing of N. meningitidis disease causing (A, B, C, W, X, Y) sequence types in year 10, 11, and 12 students at baseline and at 12 months. In schools randomized to Group A, describe the association of carriage prevalence of disease causing genogroups and vaccine uptake at school level following implementation. In schools randomized to Group A, describe the association of carriage prevalence of all N. meningitidis and vaccine uptake at school level following implementation.

Official Title
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South Australian Meningococcal B Vaccine Herd Immunity Study

Conditions
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Meningococcal Disease

Intervention / Treatment
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* Biological: Licensed 4CMenB vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: South Australian secondary school students in years 10, 11, and 12 in 2017 Written parental consent for those under the age of 18 Written student consent assent for those under the age of 18 (or if 18 years old and older consent for themselves) Available at school for at least the first pharyngeal swab and willing to comply with study procedures Exclusion Criteria: Previous anaphylaxis following any component of Bexsero vaccine Previous receipt of meningococcal B vaccine (Bexsero) Known pregnancy

Ages Eligible for Study
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Minimum Age: 14 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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A cluster randomised controlled trial to assess the impact of meningococcal B vaccine 4CMenB on nasopharyngeal carriage of N. Meningitidis
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A<br>Students within schools randomised to group A will receive two doses of licensed 4CMenB vaccine after baseline oropharyngeal swab with an interval of 1 to 2 months between doses, with the first dose given at the baseline visit in 2017. | Biological: Licensed 4CMenB vaccine<br>* Two doses (0.5 mL each) of Bexsero ® vaccine at least 1 month to <3 months apart in adolescents.<br>* Other names: Bexsero®;|
| No Intervention: Group B<br>Students within schools randomised to group B will receive the licensed 4CMenB vaccine following completion of baseline and 12 month oropharyngeal swab in 2018. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of all disease causing genogroups of N. meningitidis (A, B, C, W, X, Y) | As measured by PCR at 12 months in vaccinated and unvaccinated year 10 and 11 school students | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of each N. meningitidis genogroup (A, B, C, W, X, Y) | As measured by PCR at the 12 month pharyngeal swab in vaccinated and unvaccinated year 10 and 11 school students | 12 months | 
| Prevalence of all N. meningitidis genogroups | As measured by PCR at the 12 month pharyngeal swab in vaccinated and unvaccinated year 10 and 11 school students | 12 months | 
| Acquisition of disease causing N. meningitidis (A, B, C, W, X, Y) genogroups (negative at baseline, positive at 12 month followup) | As measured by PCR in vaccinated and unvaccinated year 10 and 11 school students | 12 months | 
| Acquisition of all N. meningitidis | As measured by PCR in vaccinated and unvaccinated year 10 and 11 school students | 12 months | 
| Risk factors associated with carriage prevalence of all N. meningitidis | As measured by PCR at baseline and 12 months | Baseline and 12 months | 
| Risk factors associated with carriage prevalence of disease causing N. meningitidis | As measured by PCR at baseline and 12 months | Baseline and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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meningococcal B vaccine, herd immunity, adolescents, young adults, south australia