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

NCT05294588 | Completed Phase 2 DMC FDA Drug

• 3 other identifiers: 21-0498DMID 21-0018U01AI162457-01
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

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.

Conditions

Gonorrhea Male

Keywords

4CMenB; Bexsero; vaccine; controlled human infection model; Neisseria gonorrhoeae

Outcome Measures

Primary Outcomes (1)

• Infectivity of N. gonorrhoeae inoculum

  Infectivity is defined as the proportion of participants positive for N. gonorrhoeae by N. gonorrhoeae Nucleic acid amplification tests (NAAT) or urine culture or swab culture on the post-inoculation antibiotic treatment day in each study group (control and experimental).

  between 1 and 10 days after N. gonorrhoeae inoculation (between study day 58 and study day 123)

Secondary Outcomes (3)

• Proportion of participants that develop macroscopic urethritis

  between 1 and 10 days after N. gonorrhoeae inoculation (between study day 58 and study day 123)

• Proportion of participants that develop symptomatic microscopic urethritis

  between 1 and 10 days after N. gonorrhoeae inoculation (between study day 58 and study day 123)

• Time to develop macroscopic urethritis

  between 1 and 10 days after N. gonorrhoeae inoculation (between study day 58 and study day 123)

Study Arms (2)

Experimental arm

EXPERIMENTAL

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.

Drug: Cefixime; Drug: Ceftriaxone; Drug: Ciprofloxacin; Biological: Neisseria gonorrhoeae strain FA1090; Biological: Meningococcal Group B Vaccine; Biological: Influenza Vaccine; Biological: Tetanus-diptheria Vaccine

Control arm

OTHER

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.

Drug: Cefixime; Drug: Ceftriaxone; Drug: Ciprofloxacin; Biological: Neisseria gonorrhoeae strain FA1090; Biological: Meningococcal Group B Vaccine; Biological: Influenza Vaccine; Biological: Tetanus-diptheria Vaccine

Interventions

Cefixime 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.

Control arm; Experimental arm

Ceftriaxone 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.

Control arm; Experimental arm

Ciprofloxacin 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

Control arm; Experimental arm

Neisseria gonorrhoeae strain FA1090 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.

Control arm; Experimental arm

Meningococcal Group B Vaccine BIOLOGICAL

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

Also known as: Bexsero, 4-component Neisseria meningitidis group B vaccine, 4CMenB

Control arm; Experimental arm

Influenza Vaccine BIOLOGICAL

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

Also known as: Flulaval

Control arm; Experimental arm

Tetanus-diptheria Vaccine BIOLOGICAL

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

Also known as: TDVAX

Control arm; Experimental arm

Eligibility Criteria

• Age: 18 Years - 35 Years
• Gender Eligibility Details: Participants assigned male sex at birth any race or ethnicity
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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
• 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.
• 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

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

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, 27599-7215, United States

Location

Related Publications (1)

• 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.

  PMID: 40086037 DERIVED

MeSH Terms

Interventions

Cefixime; Ceftriaxone; Ciprofloxacin; 4CMenB vaccine; Influenza Vaccines; FluLaval

Intervention Hierarchy (Ancestors)

Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Joseph A Duncan, MD, PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Participants and laboratory and clinical staff conducting Ng challenge and assessment of infection and immune responses will be blinded to study arm assignment. Randomization group assignments will be maintained throughout the study.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study intervention is vaccination with two doses of BEXSERO™and with 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. Participants assigned to the control arm of the study receive immunization with control vaccinations prior to Neisseria gonorrhoeae challenge and with BEXSERO™after Neisseria gonorrhoeae challenge. Participants assigned to the experimental arm of the study receive immunization with BEXSERO™ prior to Neisseria gonorrhoeae challenge and with after control vaccinations Neisseria gonorrhoeae challenge.

Study Record Dates

• First Submitted: March 15, 2022
• First Posted: March 24, 2022
• Study Start: April 18, 2022
• Primary Completion: February 5, 2026
• Study Completion: February 5, 2026
• Last Updated: March 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 12-24 months after completion
• Access Criteria: Investigator/researcher who proposes to use the data IRB, IEC, or REB approval and an executed data use/sharing agreement with UNC.

Locations

US (1)