Efficacy of Immunization With 4C-MenB in Preventing Experimental Urethral Infection With Neisseria Gonorrhoeae

  • STATUS
    Recruiting
  • End date
    Feb 5, 2028
  • participants needed
    140
  • sponsor
    University of North Carolina, Chapel Hill
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Updated on 5 June 2022
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Summary

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 vaccinesseasonal 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.

Description

The study is a single-site, double-blind randomized controlled trial to test whether vaccination with 4C-MenB, BEXSERO™ (approved for protection against invasive disease with group B Neisseria meningitidis), according to the FDA-approved schedule , provides protection from urethral infection with Neisseria gonorrhoeae in the controlled human male gonococcal infection model. The study will be conducted in 3 phases: 1) initial vaccination phase, 2) Neisseria gonorrhoeae challenge phase, and 3) post-challenge vaccination phase.

The study intervention is vaccination with two doses of BEXSERO™ and two commercially available FDA-approved vaccines that do not have relevance to Neisseria gonorrhoeae: quadrivalent influenza (FLULAVAL™) and tetanus/diphtheria (TDVAX™). At enrollment, participants are randomized in a 1:1 ratio to the control vaccine arm or the experimental vaccine arm. All participants receive two immunizations prior to the bacterial challenge phase and two immunizations in the post-challenge phase. Individuals assigned to the experimental arm receive two doses of BEXSERO™ prior to Neisseria gonorrhoeae challenge and control vaccines in the post-challenge vaccination phase. Participants assigned to the control arm receive FLULAVAL™ and TDVAX™ prior to challenge and BEXSERO™ in the post-challenge vaccination phase. Primary and secondary outcomes are determined following bacterial challenge. This study design provides clinical equipoise, because all participants receive the known benefits associated with administration of BEXSERO™ for protection against meningococcal disease.

For bacterial challenge, all participants receive a suspension containing 10^6 colony-forming units of Neisseria gonorrhoeae strain FA1090 delivered to the anterior urethra. This dose has been shown to produce symptomatic gonococcal urethritis in 80-90% of unvaccinated, exposed participants within 5 days after bacterial inoculation. Participants are followed with daily visits to assess for development of urethritis and presence of Neisseria gonorrhoeae in their urine. Participants receive 100% effective antibiotic treatment 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 after urethral inoculation with bacterial product, regardless of infection status.

Details
Condition Gonorrhea Male
Treatment Ciprofloxacin, ceftriaxone, Influenza vaccine, Cefixime, Meningococcal group B vaccine, Neisseria gonorrhoeae strain FA1090, Tetanus-diptheria Vaccine
Clinical Study IdentifierNCT05294588
SponsorUniversity of North Carolina, Chapel Hill
Last Modified on5 June 2022

Eligibility

 Yes No Not Sure

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
% 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
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