Efficacy Study of 4CMenB (Bexsero®) to Prevent Gonorrhoea Infection in Gay and Bisexual Men

NCT ID: NCT04415424

Last Updated: 2025-03-24

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 650 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-08
• Study Completion Date: 2025-10-30

Brief Summary

This is a Phase 3, double-blinded, randomised placebo-controlled, multi-centred trial evaluating the efficacy of the four-component meningococcal B vaccine, 4CMenB (Bexsero®), in the prevention of Neisseria gonorrhoeae infection.The targeted population is 18-50 years-old men (cis and trans), trans women and non-binary people who have sex with men (hereafter referred to as Gay Bisexual Men+ [GBM+], either HIV-negative and taking pre-exposure prophylaxis [PrEP], or HIV-positive with undetectable viral load <200copies/ml and a cluster of differentiation 4 [CD4] count >350 cells/cmm) who have high N. gonorrhoeae incidence and are recommended by Australian guidelines to have regular, comprehensive sexual health screening. 730 participants will be enrolled and randomised 1:1 and stratified by clinical sites to receive two doses of 4CMenB vaccine or a matching placebo at 0 and 3 months by intramuscular injection. Recruitment is for 12 months and all participants will be follow-up 3-monthly for a period of 2 years. The trial aims to evaluate the efficacy of 4CMenB in the prevention of N. gonorrhoeae infection.

Detailed Description

This is a Phase 3, double-blinded, randomised placebo-controlled, multi-centred trial evaluating the efficacy of the four-component meningococcal B vaccine, 4CMenB (Bexsero®), in the prevention of Neisseria gonorrhoeae infection.The target population for this trial is GBM+, either HIV-negative and on PrEP or HIV-positive, who had a diagnosis of gonorrhoea or infectious syphilis in the last 18 months (a key characteristic associated with greater gonorrhoea risk). This population has the highest known gonococcal incidence and are recommended under Australian guidelines to attend clinics 3-monthly for comprehensive sexual health screening, including Nuclei acid amplification test (NAAT)-based screening of urine, and pharyngeal and anal specimens for N. gonorrhoeae infection. 730 participants will be enrolled and randomised 1:1 and stratified by clinical sites to receive two doses of 4CMenB vaccine or a matching placebo at 0 and 3 months by intramuscular injection. Recruitment will occur over a 12-month period and all participants will be followed up 3-monthly over a period of 2 years. Participants, their study clinicians and study researchers assessing the outcomes will be blinded to the treatment arm (vaccine or placebo). Participants will be required to attend approximately 10 study visits. Participants may attend additional visits if they have been diagnosed with gonorrhoea infection (symptomatic or asymptomatic) or have a postitive gonorrhoea NAAT test when they return for test of cure. Potentially eligible individuals will be screened within 14 days of baseline (the visit when the first dose of study treatment is administered). Randomisation can be conducted any time between screening and baseline. Screening, randomisation and baseline can occur on the same day if the required HIV result(s) and drug kit (containing 4CMenB or placebo) are available for a participant in the clinic. At screening, study clinicians will conduct the informed consent process with a participant and the informed consent will be signed by both the study clinician and the participant. Eligibility criteria will be checked and a review of medical history (including vaccination history for 4CMenB, prior known meningococcal disease, recent history of sexually transmitted infections [STIs], history of taking PrEP [for HIV negative individuals] as well as antibiotic use in the last 3 months) will be conducted. Routine blood, urine and swabs will be collected, and urine pregnancy test will be performed in participants with child-bearing potential. Symptoms of urethritis, proctitis, epididymitis, and cervicitis/vaginitis will be documented. At randomisation (which can occur anytime within screening an baseline), participants will be randomised to receive either the 4CMenB vaccine or the placebo. At the baseline visit, research blood specimen and an oral mucosal exudate swab for immune responses testing will be collected before the administration of the first dose of the study treatment. A 10-minute study questionnaire will be completed by the participants. Participants will return to their study site 3 months after the first dose of study treatment to receive the second dose. Prior to the treatment administration, urine pregnancy test (in participants with child-bearing potential) will be conducted. Symptoms of urethritis, proctitis, epididymitis, and cervicitis/vaginitis will be documented. History of antibiotic use in the last 3 months will also be collected. If a participant has tested positive for gonorrhoea infection, routinely collected culture isolates and NAAT samples will be stored in a study research laboratory for phenotypic antimicrobial resistance (AMR) testing and genotyping. Routine blood, urine and swabs will also be collected. Adverse events and serious adverse events (SAEs) will be recorded but only SAEs will be entered into the study electronic data capture system, and reported to the Sponsor in real time. Three-monthly visits will be conducted over a period of 2 years. The study aims to evaluate the efficacy of 4CMenB in the prevention of N. gonorrhoeae infection.

Conditions

Neisseria Gonorrheae Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Treatment arm A - 4CMenB vaccine

4CMenB vaccine will be administered as an intramuscular injection in 0.5 ml single-dose pre-filled syringe in two doses with 3-month apart (at Baseline and Month 3 visit).

Group Type: EXPERIMENTAL

4CMenB vaccine

Intervention Type: BIOLOGICAL

A four-component meningococcal B vaccine

Treatment arm B - placebo

Placebo will be administered as an intramuscular injection in 0.5 ml single dose pre-filled syringe in two doses with 3-month apart (at Baseline and Month 3 visit).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

0.5 ml of 150 mmol sodium chloride (0.9% saline solution)

Interventions

4CMenB vaccine

A four-component meningococcal B vaccine

Intervention Type: BIOLOGICAL

Placebo

0.5 ml of 150 mmol sodium chloride (0.9% saline solution)

Intervention Type: OTHER

Other Intervention Names

Bexsero®

Eligibility Criteria

Inclusion Criteria

1. Between 18 to ≤ 50 years of age

2. Men (cis and trans), trans women and non-binary people who have had sex with at least one man in the last 6 months

3. Diagnosis of gonorrhoea or infectious syphilis in the last 18 months

4. Committed not to take doxycycline as prophylaxis for the duration of the trial

5. Able to understand spoken and written English

6. Willing and likely to comply with the trial procedures for 2 years

7. Agree to be contacted via short message service (SMS)/phone/ email by the study team

AND EITHER

1. HIV-negative (with an HIV negative antibody test within 4 months of screening) and taking HIV PrEP (daily PrEP or on-demand PrEP) within the last 4 months at the time of enrolment or

2. HIV-positive and on an antiviral regimen, with an undetectable virus level of <200 copies/ml and a CD4 count >350 cells/cmm (to optimise the immune response to vaccine) within 12 months of screening

Exclusion Criteria

1. Have a previous history of vaccination for meningococcal B with 4CMenB

2. Have contraindications to receiving the meningococcal B vaccine which include:

• Anaphylaxis following a previous dose of any meningococcal vaccine
• Anaphylaxis following any vaccine component

3. Are participating in biomedical prevention strategies for bacterial STIs (participation in diagnostic or treatment studies is not an exclusion)

4. Are taking long-term (> 4 weeks) antibiotic for prophylaxis or treatment for acne, malaria, syphilis or other bacterial condition(s)

5. Have defects in, or deficiency of, complement components, including factor H, factor D or properdin deficiency

6. Are taking or will receive complement inhibitors such as eculizumab (a monoclonal antibody directed against complement component C5) or ravulizumab

7. Have functional or anatomical asplenia, including sickle cell disease or other haemoglobinopathies, and congenital or acquired asplenia

8. Have had a haematopoietic stem cell transplant

9. 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)

10. Documented allergy to latex and/or kanamycin

11. Have prior known meningococcal disease

12. Positive pregnancy test at screening

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Griffith University

OTHER

Sponsor Role: collaborator

Kirby Institute

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Professor Kate Seib, BSc(Hon),PhD

Role: STUDY_CHAIR

Institute for Glycomics, Griffith University, Queensland, Australia

Professor Basil Donovan, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

The Kirby Institute, University of New South Wales Sydney, Australia

Professor Andrew Grulich, MBBS, PhD

Role: PRINCIPAL_INVESTIGATOR

The Kirby Institute, University of New South Wales Sydney, Australia

Locations

Western Sydney Sexual Health Centre

Parramatta, New South Wales, Australia

Sydney Sexual Health Centre

Sydney, New South Wales, Australia

Taylor Square Private Clinic

Sydney, New South Wales, Australia

RPA Sexual Health

Sydney, New South Wales, Australia

Gold Coast Sexual Health Service

Southport, Queensland, Australia

Melbourne Sexual Health Centre

Carlton, Victoria, Australia

Prahran Market Clinic

Melbourne, Victoria, Australia

Countries

Australia

References

Seib KL, Donovan B, Thng C, Lewis DA, McNulty A, Fairley CK, Yeung B, Jin F, Fraser D, Bavinton BR, Law M, Chen MY, Chow EPF, Whiley DM, Mackie B, Jennings MP, Jennison AV, Lahra MM, Grulich AE. Multicentre double-blind randomised placebo-controlled trial evaluating the efficacy of the meningococcal B vaccine, 4CMenB (Bexsero), against Neisseria gonorrhoeae infection in men who have sex with men: the GoGoVax study protocol. BMJ Open. 2024 Apr 16;14(4):e081675. doi: 10.1136/bmjopen-2023-081675.

Reference Type: DERIVED

PMID: 38626958 (View on PubMed)

Other Identifiers

APP1182443

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

HEPP2001

Identifier Type: -

Identifier Source: org_study_id