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

NCT ID: NCT05294588

Last Updated: 2025-03-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-18
• Study Completion Date: 2028-02-29

Brief 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 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.

Detailed 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.

Conditions

Gonorrhea Male

Study Design

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

Study Groups

Experimental arm

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 Type: EXPERIMENTAL

Cefixime

Intervention Type: DRUG

Mandatory rescue therapy consisting of cefixime 400 mg orally in a single dose: on patient request, at the onset of clinically apparent urethritis or on the 10th study day after inoculation.

Ceftriaxone

Intervention Type: DRUG

Mandatory rescue therapy consisting of ceftriaxone 250 mg intramuscularly in a single dose: on patient request, at the onset of clinically apparent urethritis or on the 10th study day after inoculation.

Ciprofloxacin

Intervention Type: DRUG

Mandatory antibiotic treatment failure therapy: Ciprofloxacin 500 mg orally in a single dose: if the subject has a positive N. gonorrhoeae test within 1 week post initial antibiotic treatment

Neisseria gonorrhoeae strain FA1090

Intervention Type: BIOLOGICAL

0.4 mL of a suspension containing 10\^5 - 10\^6 CFU of Neisseria gonorrhoeae, in phosphate-buffered saline, delivered to the anterior urethra through a No.8 pediatric French catheter.

Meningococcal Group B Vaccine

Intervention Type: BIOLOGICAL

All participants will receive 2 doses of the 4CMenB vaccine, 0.5 mL intramuscularly

Influenza Vaccine

Intervention Type: BIOLOGICAL

All participants will receive the quadrivalent influenza vaccine, 0.5 mL intramuscularly.

Tetanus-diptheria Vaccine

Intervention Type: BIOLOGICAL

All participants will receive the Td vaccine, 0.5 mL intramuscularly.

Control arm

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.

Group Type: OTHER

Cefixime

Intervention Type: DRUG

Mandatory rescue therapy consisting of cefixime 400 mg orally in a single dose: on patient request, at the onset of clinically apparent urethritis or on the 10th study day after inoculation.

Ceftriaxone

Intervention Type: DRUG

Mandatory rescue therapy consisting of ceftriaxone 250 mg intramuscularly in a single dose: on patient request, at the onset of clinically apparent urethritis or on the 10th study day after inoculation.

Ciprofloxacin

Intervention Type: DRUG

Mandatory antibiotic treatment failure therapy: Ciprofloxacin 500 mg orally in a single dose: if the subject has a positive N. gonorrhoeae test within 1 week post initial antibiotic treatment

Neisseria gonorrhoeae strain FA1090

Intervention Type: BIOLOGICAL

0.4 mL of a suspension containing 10\^5 - 10\^6 CFU of Neisseria gonorrhoeae, in phosphate-buffered saline, delivered to the anterior urethra through a No.8 pediatric French catheter.

Meningococcal Group B Vaccine

Intervention Type: BIOLOGICAL

All participants will receive 2 doses of the 4CMenB vaccine, 0.5 mL intramuscularly

Influenza Vaccine

Intervention Type: BIOLOGICAL

All participants will receive the quadrivalent influenza vaccine, 0.5 mL intramuscularly.

Tetanus-diptheria Vaccine

Intervention Type: BIOLOGICAL

All participants will receive the Td vaccine, 0.5 mL intramuscularly.

Interventions

Cefixime

Mandatory rescue therapy consisting of cefixime 400 mg orally in a single dose: on patient request, at the onset of clinically apparent urethritis or on the 10th study day after inoculation.

Intervention Type: DRUG

Ceftriaxone

Mandatory rescue therapy consisting of ceftriaxone 250 mg intramuscularly in a single dose: on patient request, at the onset of clinically apparent urethritis or on the 10th study day after inoculation.

Intervention Type: DRUG

Ciprofloxacin

Mandatory antibiotic treatment failure therapy: Ciprofloxacin 500 mg orally in a single dose: if the subject has a positive N. gonorrhoeae test within 1 week post initial antibiotic treatment

Intervention Type: DRUG

Neisseria gonorrhoeae strain FA1090

0.4 mL of a suspension containing 10\^5 - 10\^6 CFU of Neisseria gonorrhoeae, in phosphate-buffered saline, delivered to the anterior urethra through a No.8 pediatric French catheter.

Intervention Type: BIOLOGICAL

Meningococcal Group B Vaccine

All participants will receive 2 doses of the 4CMenB vaccine, 0.5 mL intramuscularly

Intervention Type: BIOLOGICAL

Influenza Vaccine

All participants will receive the quadrivalent influenza vaccine, 0.5 mL intramuscularly.

Intervention Type: BIOLOGICAL

Tetanus-diptheria Vaccine

All participants will receive the Td vaccine, 0.5 mL intramuscularly.

Intervention Type: BIOLOGICAL

Other Intervention Names

Bexsero; 4-component Neisseria meningitidis group B vaccine; 4CMenB; Flulaval; TDVAX

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joseph A Duncan, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

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

Site Status: RECRUITING

Countries

United States

Central Contacts

Joseph A Duncan, MD, PhD

Role: CONTACT

joseph_duncan@med.unc.edu

919-843-0715

Arlene Sena-Soberano, MD, MPH

Role: CONTACT

arlene_soberano@med.unc.edu

919- 966-2536

Facility Contacts

Allyson Adamo, RN, BSN

Role: primary

Allyson_Adamo@med.unc.edu

919-966-8353

References

Firth C, Emary K, Stuart A, Browne R, Williamson M, Francis E, Vanderslott S, Hodgson SH. Acceptability of the gonorrhoea human challenge model to accelerate vaccine development in UK men. Vaccine. 2025 Apr 30;54:127013. doi: 10.1016/j.vaccine.2025.127013. Epub 2025 Mar 13.

Reference Type: DERIVED

PMID: 40086037 (View on PubMed)

Other Identifiers

DMID 21-0018

Identifier Type: OTHER

Identifier Source: secondary_id

U01AI162457-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

21-0498

Identifier Type: -

Identifier Source: org_study_id