Testing a vaccine to prevent gonorrhea infection in men

Division of Microbiology and Infectious Diseases, (DMID) 21-0018: Efficacy of Immunization With 4C-MenB in Preventing Experimental Urethral Infection With Neisseria Gonorrhoeae

This study is testing if the 4C-MenB vaccine can help prevent gonorrhea infections in men aged 18 to 36.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 140 (estimated)
• Ages: 18 Years to 35 Years
• Sex: Male
• Sponsor: University of North Carolina, Chapel Hill (other)
• Drugs / interventions: Methotrexate
• Locations: 1 site (Chapel Hill, North Carolina)
• Trial ID: NCT05294588 on ClinicalTrials.gov

What this trial studies

This is a double-blind randomized controlled trial aimed at evaluating the efficacy of the 4C-MenB vaccine, BEXSERO™, in preventing urethral infections caused by Neisseria gonorrhoeae. The study will involve male participants aged 18 to 36 who will receive two doses of the vaccine or control vaccines before and after being exposed to the bacteria in a controlled setting. The trial will assess the vaccine's protective effects through a structured challenge phase and follow-up evaluations. The findings could contribute to the development of effective vaccines against gonorrhea.

Who should consider this trial

Good fit: Ideal candidates are healthy males aged 18 to 36 with no prior vaccination against Neisseria meningitidis serogroup B.

Not a fit: Patients with a history of MenB vaccination or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to a vaccine that effectively prevents gonorrhea infections in men.

How similar studies have performed: While this approach is innovative, similar studies have not been widely conducted, making this a novel investigation.

Eligibility criteria

Inclusion Criteria:

Participants must meet all the inclusion criteria to participate in the study.

* Assigned male at birth and now ≥ 18 and \< 36 years old
* No history of prior Neisseria meningitidis serogroup B (MenB) vaccination
* Able and willing to be located easily by providing street address and telephone number (land line and/or cell phone number)
* Willingness to provide written informed consent
* Informed consent obtained and signed
* Able and willing to attend all study visits
* Able and willing to abstain from all sexual activity involving contact with the participant's penis, urine, or semen and a person other than the participant during experimental gonococcal infection phase until the follow-up test for gonorrhea is negative
* Able and willing to abstain from scheduled immunizations other than those provided through the study, between enrollment and completion of Ng challenge.
* No clinically significant abnormalities on physical exam
* Urinalysis: leukocyte esterase and WBC values within normal limits
* 50% complement hemolytic activity (CH50) within normal limits (WNL)
* Negative HIV and syphilis test results at the screening visit
* Denies history of bleeding diathesis
* Denies history of seizures (due to reports of seizures with ciprofloxacin), history of childhood febrile seizure acceptable
* Denies history of cancer, except basal cell carcinoma of the skin \>5 years ago
* Denies current drug abuse that would interfere with study activities
* Denies history of penile, urethral, prostate, testis and associated structures surgery (varicocele repair, vasectomy, and vasectomy repair are acceptable if greater than 1 year prior to enrollment)

Exclusion Criteria:

Participants meeting any of the exclusion criteria at initial screening and screening prior to Ng challenge will be excluded from study participation. If the results of Complete blood count (CBC), serum alanine transaminase (ALT), serum creatinine, or urinalysis obtained at initial screening are outside acceptable limits, and the clinician judges the deviation unlikely to be clinically relevant, one-time repeat screening is permitted. Acceptable laboratory values are presented in Appendix B.15

* Student or employee under the direct supervision of any of the study investigators
* Any known immunodeficiencies, including complement deficiency, antibody deficiency, chronic granulomatous disease or HIV infection
* A history of prior confirmed N. meningitidis infection
* Hemophilia or other bleeding diatheses.
* Autoimmune disorders; mild autoimmune disorders, such as eczema, are not exclusionary and will be determined by the study physician.
* Unstable psychiatric condition (defined as receiving either \<3 months of the same medication (and dose) or a decompensating event during the previous 3 months) or psychiatric condition that, in the opinion of the investigator, will compromise the participant's ability to comply with protocol requirements
* Known anatomic abnormality of the urethra or urethral meatus (granular hypospadias is not exclusionary if the study physician believes that the urethral location will not interfere with inoculation catheter insertion)
* Any immunization in 28 days prior to enrollment
* Self-reported treatment for cancer within the past year
* Receipt of anticoagulants (aspirin or nonsteroidal anti-inflammatory drugs (NSAIDS) are acceptable) within 14 days prior to study entry.
* Use of any systemic immunomodulatory treatment, systemic corticosteroids, (inhaled and topical corticosteroids acceptable), investigational products, interleukins, interferons, growth factors, or intravenous immunoglobulin (IVIG) within 45 days prior to study entry.
* 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.
* Allergy to penicillin, cephalosporins or ciprofloxacin or to lidocaine or any component of 4C-MenB vaccine or control vaccines (flu, Influenza vaccine (FLULAVALTM) and Td, TDVAXTM), including latex (confirmed delayed contact hypersensitivity to latex is not exclusionary)
* Treatment with medications that are contraindicated with cefixime, ceftriaxone or ciprofloxacin and that cannot be withheld for the single doses given in this study
* Serum creatinine level \> 1.1X upper limit of normal (ULN) and deemed clinically significant by the study physician
* Serum ALT level \> 1.25X ULN and deemed clinically significant by the study physician
* WBC count \< 2.5 or \> 15.0 x109/L and deemed clinically significant by the study physician
* Absolute neutrophil count (ANC) \< 1.0 x 109/L and deemed clinically significant by the study physician
* Hemoglobin level \< 11.0 g/dL or above ULN and deemed clinically significant by the study physician
* Urinalysis: Qualitative protein level ≥ 1+ or Red blood cell (RBC) count≥ 6/hpf
* Any condition in the opinion of the investigator that would interfere with the proper conduct of the trial.

Medications not permitted with cefixime or ceftriaxone:

Warfarin Probenecid Aspirin Diuretics such as furosemide Aminoglycoside antibiotics Chloramphenicol

Medications not permitted with ciprofloxacin:

Tizanidine Theophylline Warfarin Glyburide Cyclosporine Probenecid Phenytoin Methotrexate Antacids, multivitamins, and other dietary supplements containing magnesium, calcium, aluminum, iron or zinc Caffeine-containing medications Sucralfate or didanosine chewable or buffered tablets

Where this trial is running

Chapel Hill, North Carolina

• Clinical and Translational Research Center (CTRC) at University of North Carolina (UNC) Hospitals and/or at UNC Global Clinical Research North — Chapel Hill, North Carolina, United States (RECRUITING)

Study contacts

• Principal investigator: Joseph A Duncan, MD, PhD — University of North Carolina, Chapel Hill
• Study coordinator: Joseph A Duncan, MD, PhD

Conditions: Gonorrhea Male, 4CMenB, Bexsero, vaccine, controlled human infection model, Neisseria gonorrhoeae