Clinical trial NCT03089086: South Australian Meningococcal B Vaccine Herd Immunity Study
Official title: South Australian Meningococcal B Vaccine Herd Immunity Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Meningococcal Disease
Keywords: meningococcal B vaccine
herd immunity
adolescents
young adults
south australia
Lead sponsor: University of Adelaide
Sponsor class: OTHER
Collaborators: name: SA Health
First posted: 2017-03-24
Enrollment: 34489
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A cluster randomised controlled trial to assess the impact of meningococcal B vaccine 4CMenB on nasopharyngeal carriage of N. Meningitidis
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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:

1. Previous anaphylaxis following any component of Bexsero vaccine
2. Previous receipt of meningococcal B vaccine (Bexsero)
3. Known pregnancy

Primary outcomes:
measure: Prevalence of all disease causing genogroups of N. meningitidis (A, B, C, W, X, Y)
timeFrame: 12 months
Secondary outcomes:
measure: Prevalence of each N. meningitidis genogroup (A, B, C, W, X, Y)
timeFrame: 12 months
measure: Prevalence of all N. meningitidis genogroups
timeFrame: 12 months
measure: Acquisition of disease causing N. meningitidis (A, B, C, W, X, Y) genogroups (negative at baseline, positive at 12 month followup)
timeFrame: 12 months
measure: Acquisition of all N. meningitidis
timeFrame: 12 months
measure: Risk factors associated with carriage prevalence of all N. meningitidis
timeFrame: Baseline and 12 months
measure: Risk factors associated with carriage prevalence of disease causing N. meningitidis
timeFrame: Baseline and 12 months
Other outcomes:
measure: Age specific IMD attack rates
timeFrame: Prior to and following implementation of the intervention
measure: Carriage density of N. meningitidis (all genogroups)
timeFrame: Baseline and 12 months
measure: Description of whole genome sequences of carriage isolates
timeFrame: Baseline and 12 months
measure: Whole genogroup sequencing of all carriage isolates
timeFrame: Baseline and 12 months
measure: Vaccine uptake and carriage prevalence of all N. meningitidis.
timeFrame: 12 months
measure: Vaccine uptake and carriage prevalence of disease causing N. meningitidis.
timeFrame: 12 months
Locations:
city: North Adelaide
country: Australia
facility: Vaccinology & Immunology Research Trials Unit
state: South Australia
Study officials:
affiliation: University of Adelaide
name: Helen Marshall
role: PRINCIPAL_INVESTIGATOR
References:
citation: Marshall HS, McMillan M, Koehler A, Lawrence A, MacLennan JM, Maiden MCJ, Ramsay M, Ladhani SN, Trotter C, Borrow R, Finn A, Sullivan T, Richmond P, Kahler CM, Whelan J, Vadivelu K. B Part of It protocol: a cluster randomised controlled trial to assess the impact of 4CMenB vaccine on pharyngeal carriage of Neisseria meningitidis in adolescents. BMJ Open. 2018 Jul 10;8(7):e020988. doi: 10.1136/bmjopen-2017-020988.
citation: McMillan M, Wang B, Koehler AP, Sullivan TR, Marshall HS. Impact of Meningococcal B Vaccine on Invasive Meningococcal Disease in Adolescents. Clin Infect Dis. 2021 Jul 1;73(1):e233-e237. doi: 10.1093/cid/ciaa1636.
citation: Marshall HS, Koehler AP, Wang B, A'Houre M, Gold M, Quinn H, Crawford N, Pratt N, Sullivan TR, Macartney K. Safety of meningococcal B vaccine (4CMenB) in adolescents in Australia. Vaccine. 2020 Aug 18;38(37):5914-5922. doi: 10.1016/j.vaccine.2020.07.009. Epub 2020 Jul 22.
citation: McMillan M, Walters L, Sullivan T, Leong LEX, Turra M, Lawrence A, Koehler AP, Finn A, Andrews RM, Marshall HS. Impact of Meningococcal B (4CMenB) Vaccine on Pharyngeal Neisseria meningitidis Carriage Density and Persistence in Adolescents. Clin Infect Dis. 2021 Jul 1;73(1):e99-e106. doi: 10.1093/cid/ciaa610.
citation: Marshall HS, McMillan M, Koehler AP, Lawrence A, Sullivan TR, MacLennan JM, Maiden MCJ, Ladhani SN, Ramsay ME, Trotter C, Borrow R, Finn A, Kahler CM, Whelan J, Vadivelu K, Richmond P. Meningococcal B Vaccine and Meningococcal Carriage in Adolescents in Australia. N Engl J Med. 2020 Jan 23;382(4):318-327. doi: 10.1056/NEJMoa1900236.