4C-MenB Vaccine for Gonorrhea

Recruiting in Palo Alto (17 mi)

Overseen by Joseph A Duncan, MD, PhD

Age: 18 - 65

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of North Carolina, Chapel Hill

Must not be taking: Warfarin, Probenecid, Theophylline, others

Disqualifiers: Immunodeficiencies, Autoimmune disorders, Cancer, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is a double-blind randomized controlled trial to test whether the group B meningitis vaccine 4 component Neisseria meningitidis serogroup B vaccine (BEXSEROTM) (4C-MenB), trade name Bexsero™), currently approved for use by the United States Food and Drug Administration (FDA) and recommended by the Centers for Disease Control and Prevention (CDC) for protection from Neisseria meningitidis infections, also protects from Neisseria gonorrhoeae infection using controlled human experimental infection to test protection. The information the investigator learn by doing this study may also help to develop a vaccine that protects individuals from having gonorrhea infection. The study population will consist of male participants \> 18 and \< 36 years old, living in central North Carolina, in general good health without a history of 4C-MenB vaccination. Approximately 120-140 participants will be enrolled. Participants will receive 2 doses of vaccine (2 doses of 4C-MenB or 2 comparator vaccines- seasonal influenza and tetanus/diptheria booster) as intramuscular injections, and then one intraurethral challenge with Neisseria gonorrhoeae. Following the challenge, participants will cross-over and receive two doses of vaccines not received prior to challenge (2 doses of 4CMenB or the 2 comparator vaccines- seasonal influenza and tetanus/diptheria booster) All participants receive all vaccinations by the end of the study and all vaccines used in this study are licensed and FDA-approved.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop all current medications, but certain medications are not allowed with the antibiotics used in the study. You should avoid medications like warfarin, probenecid, and some others listed in the trial details.

What data supports the effectiveness of the 4C-MenB vaccine (Bexsero) for treating gonorrhea?

Research suggests that the 4C-MenB vaccine, originally designed to protect against meningitis, might also offer some protection against gonorrhea. Studies have shown that similar vaccines can reduce the risk of gonorrhea, indicating potential effectiveness for 4C-MenB in this new use. ^{1 2 3 4 5}

Is the 4C-MenB (Bexsero) vaccine safe for humans?

The 4C-MenB (Bexsero) vaccine has been used safely in people aged 10-25 years, with safety data collected from reports in the Vaccine Adverse Event Reporting System (VAERS) between 2015 and 2018. It has been used in response to outbreaks and is recommended for those at increased risk of meningococcal disease. ^{6 7 8 9 10}

How is the 4C-MenB vaccine different from other treatments for gonorrhea?

The 4C-MenB vaccine, originally developed to protect against meningococcal disease, is unique because it contains multiple components that trigger an immune response, potentially offering protection against gonorrhea, a condition with limited vaccine options. This approach is novel as it repurposes a vaccine designed for a different bacterial infection to address gonorrhea. ^{6 7 8 10 11}

Eligibility Criteria

This trial is for healthy males aged 18-35 in central North Carolina who haven't been vaccinated against Neisseria meningitidis group B. Participants must consent to avoid sexual activity during certain phases, not have a history of severe reactions to antibiotics or vaccines, and be able to attend all study visits.

Inclusion Criteria

No history of prior Neisseria meningitidis serogroup B (MenB) vaccination

Denies current drug abuse that would interfere with study activities

I do not have a history of unusual bleeding.

Exclusion Criteria

Hemoglobin level < 11.0 g/dL or above ULN and deemed clinically significant by the study physician

Have donated blood or blood products within 28 days before study vaccination, plan to donate blood at any time during the study and up to 28 days after the last blood draw

Student or employee under the direct supervision of any of the study investigators

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Vaccination

Participants receive two doses of vaccines (either BEXSERO™ or control vaccines) prior to the bacterial challenge phase

4 weeks

2 visits (in-person)

Neisseria gonorrhoeae Challenge

Participants receive a suspension containing N. gonorrhoeae and are monitored for development of urethritis

1-10 days

Daily visits (in-person)

Post-Challenge Vaccination

Participants receive two doses of vaccines not received prior to the challenge (either BEXSERO™ or control vaccines)

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• 4C-MenB (Vaccine)

Trial Overview The trial tests if the FDA-approved Bexsero™ vaccine for meningitis B also prevents gonorrhea infection. It's a double-blind study where participants receive either the meningitis vaccine or other vaccines (flu and tetanus/diptheria), followed by an experimental challenge with gonorrhea bacteria.

Participant Groups

Group I: Experimental arm Experimental Treatment 7 Interventions

All participants receive two immunizations prior to the bacterial challenge phase and two immunizations after the challenge phase. Individuals assigned to the experimental arm receive the recommended two doses of BEXSERO™ prior to bacterial challenge and control vaccines (FLULAVAL™ and TDVAX™) in the post-challenge vaccination phase. For bacterial challenge, all participants receive a suspension containing 10\^6 colony-forming units of N. gonorrhoeae strain FA1090 delivered to the anterior urethra. Participants receive 100% effective antibiotic treatment for N. gonorrhoeae strain FA1090 infection when (1) requested by the participant regardless of signs, symptoms or positive cultures, (2) urethral discharge is observed by the examining clinician or reported by the participant, or (3) 10 days afterurethral inoculation with bacterial product, regardless of infection status.

Group II: Control arm Experimental Treatment 7 Interventions

All participants receive two immunizations prior to the bacterial challenge phase and two immunizations after the challenge phase. Individuals assigned to the control arm receive control vaccines that have no relevance to N. gonorrhoeae infection (FLULAVAL™ and TDVAX™) prior to bacterial challenge and then receive two doses of BEXSERO™ in the post-challenge vaccination phase. For bacterial challenge, all participants receive a suspension containing 10\^6 colony-forming units of N. gonorrhoeae strain FA1090 delivered to the anterior urethra. Participants receive 100% effective antibiotic treatment for N. gonorrhoeae strain FA1090 infection when (1) requested by the participant regardless of signs, symptoms or positive cultures, (2) urethral discharge is observed by the examining clinician or reported by the participant, or (3) 10 days afterurethral inoculation with bacterial product, regardless of infection status.

4C-MenB is already approved in European Union, United States for the following indications:

🇪🇺 Approved in European Union as Bexsero for:

• Invasive meningococcal disease caused by serogroup B

🇺🇸 Approved in United States as Bexsero for:

• Invasive meningococcal disease caused by serogroup B in adolescents and young adults aged 10 through 25 years

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Clinical and Translational Research Center (CTRC) at University of North Carolina (UNC) Hospitals and/or at UNC Global Clinical Research North Chapel Hill, NC

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill Lead Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) Collaborator

References

1. United States pubmed.ncbi.nlm.nih.gov

Effectiveness of a serogroup B outer membrane vesicle meningococcal vaccine against gonorrhoea: a retrospective observational study. [2023] Declining antimicrobial susceptibility to current gonorrhoea antibiotic treatment and inadequate treatment options have raised the possibility of untreatable gonorrhoea. New prevention approaches, such as vaccination, are needed. Outer membrane vesicle meningococcal serogroup B vaccines might be protective against gonorrhoea. We evaluated the effectiveness of a serogroup B meningococcal outer membrane vesicle vaccine (MenB-4C) against gonorrhoea in individuals aged 16-23 years in two US cities.

2. England pubmed.ncbi.nlm.nih.gov

Preventing secondary cases of invasive meningococcal capsular group B (MenB) disease using a recently-licensed, multi-component, protein-based vaccine (Bexsero(®)). [2022] To assess the potential use of a protein-based meningococcal group B (MenB) vaccine (Bexsero(®)) in addition to antibiotic chemoprophylaxis for preventing secondary cases.

3. United States pubmed.ncbi.nlm.nih.gov

Public health impact and cost-effectiveness of gonorrhoea vaccination: an integrated transmission-dynamic health-economic modelling analysis. [2022] Gonorrhoea is a rapidly growing public health threat, with rising incidence and increasing drug resistance. Evidence that the MeNZB and four-component serogroup B meningococcal (4CMenB) vaccines, designed against Neisseria meningitidis, can also offer protection against gonorrhoea has created interest in using 4CMenB for this purpose and for developing gonorrhoea-specific vaccines. However, cost-effectiveness, and how the efficacy and duration of protection affect a gonorrhoea vaccine's value, have not been assessed.

4. United States pubmed.ncbi.nlm.nih.gov

Meningococcus B Vaccination Effectiveness Against Neisseria gonorrhoeae Infection in People Living With HIV: A Case-Control Study. [2023] We assessed the vaccination effectiveness (VE) of multicomponent meningococcal serogroup B (4CMenB) vaccine against gonorrhea among people living with HIV (PLWH) with a previous diagnosis of sexually transmitted infection.

5. Switzerland pubmed.ncbi.nlm.nih.gov

Insight into Prevention of Neisseria Gonorrhoeae: A Short Review. [2022] Neisseria gonorrhoeae (gonococcus) and Neisseria meningitidis (meningococcus) are important global pathogens which cause the sexually transmitted diseases gonorrhea and meningitis, respectively, as well as sepsis. We prepared a review according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA), with the aims of (a) evaluating the data on the MenB vaccination as protection against sexually transmitted infections by N. gonorrhoeae and (b) to briefly comment on the data of ongoing studies of new vaccines. We evaluated existing evidence on the effect of 4CMenB, a multi-component vaccine, on invasive diseases caused by different meningococcal serogroups and on gonorrhea. Non-B meningococcal serogroups showed that the 4CMenB vaccine could potentially offer some level of protection against non-B meningococcal serogroups and N. gonorrhoeae. The assessment of the potential protection conferred by 4CMenB is further challenged by the fact that further studies are still needed to fully understand natural immune responses against gonococcal infections. A further limitation could be the potential differences between the protection mechanisms against N. gonorrhoeae, which causes local infections, and the protection mechanisms against N. meningitidis, which causes systemic infections.

6. Netherlands pubmed.ncbi.nlm.nih.gov

Bactericidal antibody against a representative epidemiological meningococcal serogroup B panel confirms that MATS underestimates 4CMenB vaccine strain coverage. [2019] 4CMenB (Bexsero), a vaccine developed against invasive meningococcal disease caused by capsular group B strains (MenB), was recently licensed for use by the European Medicines Agency. Assessment of 4CMenB strain coverage in specific epidemiologic settings is of primary importance to predict vaccination impact on the burden of disease. The Meningococcal Antigen Typing System (MATS) was developed to predict 4CMenB strain coverage, using serum bactericidal antibody assay with human complement (hSBA) data from a diverse panel of strains not representative of any specific epidemiology.

7. Netherlands pubmed.ncbi.nlm.nih.gov

Safety surveillance of meningococcal group B vaccine (Bexsero®), Vaccine Adverse Event Reporting System, 2015-2018. [2023] Bexsero® (GlaxoSmithKline) is a four-component Neisseria meningitidis serogroup B vaccine (MenB-4C). It was licensed in the United States in 2015 for use among individuals ages 10-25 years. We aimed to assess the post-licensure safety profile of MenB-4C by examining reports received in the Vaccine Adverse Event Reporting System (VAERS).

8. Netherlands pubmed.ncbi.nlm.nih.gov

The role of anti-NHba antibody in bactericidal activity elicited by the meningococcal serogroup B vaccine, MenB-4C. [2018] MenB-4C (Bexsero®) is a multicomponent serogroup B meningococcal vaccine. For vaccine licensure, efficacy was inferred from serum bactericidal antibody (SBA) against three antigen-specific indicator strains. The bactericidal role of antibody to the fourth vaccine antigen, Neisserial Heparin binding antigen (NHba), is incompletely understood.

9. United States pubmed.ncbi.nlm.nih.gov

Safety of a meningococcal group B vaccine used in response to two university outbreaks. [2022] To assess the safety of meningococcal group B (MenB)-4C vaccine.

10. Spain pubmed.ncbi.nlm.nih.gov

[Economic evaluation of the introduction of 4CMenB (Bexsero®) in the national vaccine schedule in Spain]. [2021] Bexsero® (4CMenB), meningococcal B vaccine, was licensed in Europe in 2013. In Spain, despite MenB being the most frequent cause of invasive meningococcal disease (IMD), Bexsero® is recommended and financed for patients at increased risk of IMD but is not financed by the NHS in the routine vaccination schedule.

11. New Zealand pubmed.ncbi.nlm.nih.gov

Multicomponent meningococcal serogroup B vaccine (4CMenB; Bexsero(®)): a review of its use in primary and booster vaccination. [2016] Multicomponent meningococcal serogroup B vaccine (4CMenB; Bexsero(®)) is a unique vaccine containing four main immunogenic components: three recombinant proteins combined with outer membrane vesicles derived from meningococcal NZ98/254 strain. After three doses of 4CMenB (administered at 2, 3, and 4 months or 2, 4, and 6 months of age) in vaccine-naive infants, the majority of infants had seroprotective human complement serum bactericidal assay (hSBA) antibody titers against the meningococcal serogroup B test strains selected to be specific for the vaccine antigens in randomized, open-label or observer-blind, multicenter, phase IIb or III trials. In extensions to the phase III trial, two doses of 4CMenB administered between 12 and 15 months of age in vaccine-naive infants, and a single booster dose of 4CMenB administered at 12 months of age in vaccine-experienced infants, also elicited robust immunogenic responses. In a phase IIb/III trial, the majority of adolescents (aged 11-17 years) achieved seroprotective hSBA antibody titers against meningococcal serogroup B test strains after two doses of 4CMenB, and a third dose did not appear to add any extra protection. In adults who were potentially at an increased risk of occupational exposure to meningococcal isolates, seroprotection rates were high after one dose of 4CMenB and increased further after two or three doses in a small noncomparative, two-center, phase II trial. The reactogenicity of 4CMenB was generally acceptable in clinical trials. However, the vaccine was associated with more solicited systemic adverse events (particularly fever) in infants when coadministered with routine infant vaccines than when these vaccines were administered alone. In conclusion, 4CMenB effectively elicited immune responses against meningococcal serogroup B test strains selected to be specific for the vaccine antigens in infants, adolescents, and adults.