Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001452785p
Ethics application status
Not yet submitted
Date submitted
21/10/2022
Date registered
14/11/2022
Date last updated
14/11/2022
Date data sharing statement initially provided
14/11/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Unravelling the protective effects of the MeNZB™ vaccine against gonorrhoea.
Scientific title
Unravelling the protective effects of the MeNZB™ vaccine against gonorrhoea in both immunologically primed and immunologically naïve adults.
Secondary ID [1] 302976 0
Nil known
Universal Trial Number (UTN)
U1111-1262-0320
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Meningococcal Disease 320021 0
Gonorrhoea 320022 0
Condition category
Condition code
Infection 317942 317942 0 0
Other infectious diseases
Infection 317943 317943 0 0
Sexually transmitted infections

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention group in this study are immunologically primed individuals (those who meet the inclusion criteria and have received two doses of MeNZB in the past). Both intervention and control groups will receive the same intervention.

The intervention administered is a primary course of Bexsero® (Multicomponent Meningococcal group B Vaccine), administered as two doses.

The dose administered is 0.5 mL of vaccine.
The duration of administration is a minimum of 30 days and maximum of 37 days between doses.

The mode of administration is via intramuscular injection, performed by a licensed vaccinator. Intervention adherence will be monitored through REDCap, research data capture software utilised in this study for participant enrolment and scheduling.

The intervention will be administered within the clinical trial space at the University of Auckland.
Intervention code [1] 319263 0
Prevention
Comparator / control treatment
The control group in this study are immunologically naive individuals (those who meet the inclusion criteria and have not received any doses of Meningoccal B vaccine in the past). Both intervention and control groups will receive the same intervention.

The intervention administered is a primary course of Bexsero® (Multicomponent Meningococcal group B Vaccine), administered as two doses.

The dose administered is 0.5 mL of vaccine.
The duration of administration is a minimum of 30 days and maximum of 37 days between doses.

The mode of administration is via intramuscular injection, performed by a licensed vaccinator. Intervention adherence will be monitored through REDCap, research data capture software utilised in this study for participant enrolment and scheduling.

The intervention will be administered within the clinical trial space at the University of Auckland.
Control group
Active

Outcomes
Primary outcome [1] 333083 0
Cellular response to gonococci assays by intracellular cytokine staining and flow cytometery.

Human peripheral blood mononuclear cells (PBMCs) from all collection times (0, 3, 7, 42 and 120 days) will be thawed and stimulated with gonococcal outer membrane vesicles (OMVs), selected highly cross-reactive gonococcal antigens, an irrelevant antigen (for example heat-killed Staphylococcus aureus) or controls for 5h and CD4+ T cells tested for production of Interleukin 2 and 17 (IL-2, IL-17), interferon gamma (IFN-g) and tumor necrosis factor (TNF) by intracellular cytokine staining.

T-cell proliferation in response to these stimuli will be quantified after 6 days using a standard tritiated-thymidine assay. Culture supernatants collected from the proliferation assay plates prior to addition of the radioactive isotope will be tested for production of cytokines by cytometric bead array. In parallel the composition and activation status of major T- and B-cell populations will be determined by multi-parameter flow cytometry using the standardised panels outlined for the Human Immunology Project.

Timepoint [1] 333083 0
Baseline, 3, 7, 30 (primary timepoint) and 120 days post-intervention.
Primary outcome [2] 333084 0
Detection of functional anti-gonococcal antibodies by bioluminescent assay, inhibition of adherence and complement component 3 b (C3b) deposition using flow cytometry.

Sera collected from naïve and immune individuals from baseline, day 30 and day 120 post-intervention will be examined for the development of functional antibody responses. The primary focus will be on development of (serum bactericidal antibody) SBA to gonorrhoea. We have developed a bioluminescent assay which can be used to rapidly measure SBA activity in immune and naïve individuals and intend to apply this assay to at least three different gonococcal isolates.

The development of other functional cross-reactive antibody responses will be assessed by testing for serum-mediated C3b deposition on gonococci using a flow cytometry-based assay and inhibition of adherence to reproductive cell lines.
Timepoint [2] 333084 0
Baseline, 30 (primary timepoint) and 120 day post-intervention.
Primary outcome [3] 333085 0
Cross-reactive antibody responses to gonococcal targets, using sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) and enzyme-linked immunosorbent assay (ELISA) assays.

Baseline and day 30 sera from naïve and immune individuals will be used to probe outer membrane vesicles (OMVs) from multiple gonococcal isolates by SDS-PAGE and western blotting. Conserved cross-reactive bands will be selected based on:
i) cross-reactivity in vaccinated but not baseline serum;
ii) presence across multiple gonococcal isolates.
Timepoint [3] 333085 0
Baseline and day 30 (primary timepoint) post intervention.
Secondary outcome [1] 415727 0
[Fourth Primary outcome]

The development of cross-reactive serum or salivary immunoglobin G (IgG) or immunoglobin A (IgA) in response to vaccination will be quantified by ELISA at days 0, 30 and 120 using gonococcal OMVs as the coating antigen.
Timepoint [1] 415727 0
Baseline, 30 (primary timepoint) and 120 day post intervention
Secondary outcome [2] 415728 0
Cellular response to meningococcal assays by intracellular cytokine staining and flow cytometery.

Human peripheral blood mononuclear cells (PBMCs) from all collection times (0, 3, 7, 42 and 120 days) will be thawed and stimulated with meningococcal outer membrane vesicles (OMVs), selected highly cross-reactive gonococcal antigens, an irrelevant antigen (for example heat-killed Staphylococcus aureus) or controls for 5h and CD4+ T cells tested for production of Interleukin 2 and 17 (IL-2, IL-17), interferon gamma (IFN-g) and tumor necrosis factor (TNF) by intracellular cytokine staining.

T-cell proliferation in response to these stimuli will be quantified after 6 days using a standard tritiated-thymidine assay. Culture supernatants collected from the proliferation assay plates prior to addition of the radioactive isotope will be tested for production of cytokines by cytometric bead array. In parallel the composition and activation status of major T- and B-cell populations will be determined by multi-parameter flow cytometry using the standardised panels outlined for the Human Immunology Project.

Timepoint [2] 415728 0
Baseline, 3, 7, 30 (primary timepoint) and 120 days post intervention
Secondary outcome [3] 415729 0
Detection of functional anti-meningococcal antibodies by bioluminescent assay, inhibition of adherence and complement component 3 b (C3b) deposition using flow cytometry.

Sera collected from naïve and immune individuals from baseline, day 30 and day 120 post-intervention will be examined for the development of functional antibody responses. The primary focus will be on development of (serum bactericidal antibody) SBA to meningococcal antigens and bacteria.
Timepoint [3] 415729 0
Baseline, 30 (primary timepoint) and 120 days post intervention

Eligibility
Key inclusion criteria
• Persons born between 01 January 1984 and 01 January 2004.
• Persons over the age of 18 years, deemed competent and capable to consent and willing and able to participate throughout the whole study
• For females of reproductive potential: use of highly effective contraception during study participation
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Have a NHI number and be willing to provide access to their NIR records
• If born or has received a vaccine overseas, be willing to give us access to their vaccination records from the country of vaccination.
Minimum age
18 Years
Maximum age
38 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Have a previous history of vaccination for meningococcal B with 4CMenB.
• Those who have already received an NMB OMV vaccine, other than the MeNZB™ vaccine.
• Those who have received a dose of any NM OMV vaccine after the end of the MeNZB period (2008).
• Have contraindications to receiving the meningococcal B vaccine which include:
o Previous anaphylactic reaction following a previous dose of any meningococcal vaccine.
o Previous anaphylactic reaction following any vaccine component.
o Immunological condition preventing participant receiving vaccination.
o Other medical condition preventing participant receiving vaccination.
• Are participating in biomedical prevention strategies for bacterial STIs.
• Are taking complement inhibitors such as eculizumab or ravulizumab.
• Have an immunological disorder; such as those with severe autoimmune disorders, AIDS patients or those undergoing immunotherapy, including chemotherapy for blood or white blood cell cancers and organ transplant recipients.
• Have any major unstable medical condition or therapy that may cause immune compromise (e.g. chemotherapy, radiation, corticosteroids [prednisone >5mg/day] within 14 days prior to screening).
• Females who are pregnant or are planning to become pregnant during the course of the investigation.
• Persons unable or unwilling to comply with study requirements for participants.

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
All participants in this study will receive the same intervention. Within this single group, participants will be divided into two arms, those who have received the MeNZB vaccine in the past (immunologically primed) and those who have not received a meningococcal B vaccine in the past (immunologically naïve).
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/01/2023
Actual
Date of last participant enrolment
Anticipated
31/07/2023
Actual
Date of last data collection
Anticipated
31/12/2023
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment outside Australia
Country [1] 23282 0
New Zealand
State/province [1] 23282 0
Auckland

Funding & Sponsors
Funding source category [1] 307387 0
University
Name [1] 307387 0
The University of Auckland
Country [1] 307387 0
New Zealand
Primary sponsor type
University
Name
The University of Auckland
Address
The University of Auckland
Faculty of Medicine and Health Science
M&HS BUILDING 507 - Bldg 507
Level 3, 3.C025
28 PARK AVE
GRAFTON
AUCKLAND 1023
New Zealand
Country
New Zealand
Secondary sponsor category [1] 314076 0
None
Name [1] 314076 0
Address [1] 314076 0
Country [1] 314076 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 307473 0
Health and Disability Ethics Committee (region TBA)
Ethics committee address [1] 307473 0
Ethics committee country [1] 307473 0
New Zealand
Date submitted for ethics approval [1] 307473 0
30/11/2022
Approval date [1] 307473 0
Ethics approval number [1] 307473 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 107354 0
A/Prof Helen Petousis-Harris
Address 107354 0
The University of Auckland,
Faculty of Medicine and Health Science,

M&HS BUILDING 507 - Bldg 507
Level 3, Room 3106
28 PARK AVE
GRAFTON
AUCKLAND 1023
New Zealand
Country 107354 0
New Zealand
Phone 107354 0
+64 9 923 2078
Fax 107354 0
Email 107354 0
[email protected]
Contact person for public queries
Name 107355 0
Jonathan Watts-Henwood
Address 107355 0
The University of Auckland,
Faculty of Medicine and Health Science,

M&HS BUILDING 507 - Bldg 507
Level 3, Room 3.C025
28 PARK AVE
GRAFTON
AUCKLAND 1023
New Zealand
Country 107355 0
New Zealand
Phone 107355 0
+64 9 923 6746
Fax 107355 0
Email 107355 0
[email protected]
Contact person for scientific queries
Name 107356 0
Jonathan Watts-Henwood
Address 107356 0
The University of Auckland,
Faculty of Medicine and Health Science,

M&HS BUILDING 507 - Bldg 507
Level 3, Room 3.C025
28 PARK AVE
GRAFTON
AUCKLAND 1023
New Zealand
Country 107356 0
New Zealand
Phone 107356 0
+64 9 923 6746
Fax 107356 0
Email 107356 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Participant data collected from this trial will be released in an aggregated form.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.