South Australian Meningococcal B Vaccine Herd Immunity Study (B Part of It)

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.

Study Overview

• Status: Completed
• Conditions: Meningococcal Disease
• Intervention / Treatment: Biological: Licensed 4CMenB vaccine

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.

• Study Type: Interventional
• Enrollment (Actual): 34489
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • North Adelaide, South Australia, Australia, 5006
      • Vaccinology & Immunology Research Trials Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A; 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; Two doses (0.5 mL each) of Bexsero ® vaccine at least 1 month to <3 months apart in adolescents.; Other Names: Bexsero®
No Intervention: Group B; 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?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age specific IMD attack rates	Age specific IMD attack rates (per 100,000 population) in all age groups in South Australia	Prior to and following implementation of the intervention
Carriage density of N. meningitidis (all genogroups)	as measured by qPCR in year 10, 11 and 12 school students at baseline and 12 months	Baseline and 12 months
Description of whole genome sequences of carriage isolates	Description of whole genome sequences of isolates known to cause disease (serogroup B, W, Y, C)	Baseline and 12 months
Whole genogroup sequencing of all carriage isolates	Description of whole genome sequences of isolates	Baseline and 12 months
Vaccine uptake and carriage prevalence of all N. meningitidis.	Carriage prevalence as measured by PCR	12 months
Vaccine uptake and carriage prevalence of disease causing N. meningitidis.	Carriage prevalence as measured by PCR	12 months

Collaborators and Investigators

• Sponsor: University of Adelaide
• Collaborators: SA Health

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2017
• Primary Completion (Actual): July 13, 2018
• Study Completion (Actual): December 31, 2018

Study Registration Dates

• First Submitted: March 17, 2017
• First Submitted That Met QC Criteria: March 17, 2017
• First Posted (Actual): March 24, 2017

Study Record Updates

• Last Update Posted (Actual): July 2, 2019
• Last Update Submitted That Met QC Criteria: June 28, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: adolescents; young adults; herd immunity; meningococcal B vaccine; south australia
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Neisseriaceae Infections; Meningococcal Infections
• Other Study ID Numbers: HREC/16/WCHN/140; ACTRN12617000079347 (Registry Identifier: Australian New Zealand Clinical Trials Registry)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified, individual participant data underlying published results will be available.
• IPD Sharing Time Frame: We estimate the data will be available from the start of 2021 for approximately 12 months.
• IPD Sharing Access Criteria: IPD will be made available on a case-by-case basis at the discretion of the International Scientific Advisory Committee and WCHN HREC. IPD data will only be available to achieve the aims in the approved proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes