Experimental Human Infection With Neisseria Gonorrhoeae (LptA Trial)

NCT04870138 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 09-0106 LptA
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, interventional, non-randomized, experimental infection model study in healthy adult males (N=up to 25) between the ages of 18-35 at study enrollment. The study is designed to test the requirements of predicted N. gonorrhoeae virulence determinants for gonococcal infection in the male urethra through infection with engineered mutants of N. gonorrhoeae. We predict that mutations abolishing expression of N. gonorrhoeae virulence determinants will eliminate or significantly reduce gonococcal infectivity or the ability to induce inflammation in an infected individual, thus identifying potential vaccine candidates. Study duration will be 1 year, and the duration for all participants will be about 3 weeks. The primary objective of the study is to compare the ability of different engineered mutants of Neisseria gonorrhoeae to cause a clinical infection (signs or symptoms of urethritis such as discomfort during urination, urethral discharge, etc.) in the male urethra.

Conditions

Gonococcal Infection

Keywords

ceftriaxone; challenge; ciprofloxacin; males; Neisseria gonorrhoeae

Outcome Measures

Primary Outcomes (3)

• The Proportion of Participants That Become Infected With Individual N. Gonorrhoeae Strains in Non-competitive Infections

  Infection defined as reported symptoms of urethritis, including urethral discharge or dysuria, plus presence of gram-negative intracellular diplococci in a urethral swab smear. The proportion of infected participants by Day 5 with N. gonorrhoeae was assessed by group among participants with non-competitive infections. Participants could become infected and received treatment any day before or on day 5.

  Day of infection, any day between Day 1 and Day 5

• The Proportion of Participants That Become Infected With Mixed Inoculum

  Infection defined as reported symptoms of urethritis, including urethral discharge or dysuria, plus presence of gram-negative intracellular diplococci in a urethral swab smear. Participants could become infected and received treatment any day before or on day 5.

  Day of infection, any day between Day 1 and Day 5

• The Proportion of Wild Type (WT) Organisms Recovered From Urine and Urethral Swab Specimens From Individual Subjects Infected With Mixed Inoculum

  Infection defined as reported symptoms of urethritis, including urethral discharge or dysuria, plus presence of gram-negative intracellular diplococci in a urethral swab smear. Participants could become infected and received treatment any day before or on day 5.

  Baseline (Day 0) and the day of infection (any day between Day 1 and Day 5)

Secondary Outcomes (24)

• EGF Cytokine Levels in Peripheral Blood

  Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)

• Eotaxin Cytokine Levels in Peripheral Blood

  Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)

• G-CSF Cytokine Levels in Peripheral Blood

  Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)

• Fractalkine Cytokine Levels in Peripheral Blood

  Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)

• GRO Cytokine Levels in Peripheral Blood

  Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)

Study Arms (3)

Mixed FA7527/FA1090

EXPERIMENTAL

Bacterial inoculum containing a mixture of equivalent numbers of the isogenic LptA mutant and wild-type (WT) strain administered once to the anterior urethra. N= up to 25

Drug: Azithromycin; Drug: Ceftriaxone; Drug: Ciprofloxacin; Biological: Neisseria gonorrhoeae strain FA1090 A26; Biological: Neisseria gonorrhoeae strain FA7527

Mutant FA7527

EXPERIMENTAL

Bacterial inoculum containing only the isogenic LptA mutant N. gonorrhoeae strain administered once to the anterior urethra. N= up to 8

Drug: Azithromycin; Drug: Ceftriaxone; Drug: Ciprofloxacin; Biological: Neisseria gonorrhoeae strain FA7527

Wild-type FA1090

EXPERIMENTAL

Bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain administered once to the anterior urethra. N= up to 8

Drug: Azithromycin; Drug: Ceftriaxone; Drug: Ciprofloxacin; Biological: Neisseria gonorrhoeae strain FA1090 A26

Interventions

Azithromycin DRUG

Alternative antibiotic treatment failure therapy: Azithromycin 2 g orally in a single dose after treatment failure with both cephalosporin and quinolone antibiotics.

Mixed FA7527/FA1090; Mutant FA7527; Wild-type FA1090

Ceftriaxone DRUG

Mandatory antibiotic treatment failure therapy: Ceftriaxone 250 mg intramuscular in a single dose on patient request, at the onset of symptoms, or on the 5th study day after inoculation.

Mixed FA7527/FA1090; Mutant FA7527; Wild-type FA1090

Ciprofloxacin DRUG

Mandatory antibiotic treatment failure therapy: Ciprofloxacin 500 mg orally in a single dose on patient request, at the onset of symptoms or on the 5th study day after inoculation.

Mixed FA7527/FA1090; Mutant FA7527; Wild-type FA1090

Neisseria gonorrhoeae strain FA1090 A26 BIOLOGICAL

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

Mixed FA7527/FA1090; Wild-type FA1090

Neisseria gonorrhoeae strain FA7527 BIOLOGICAL

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

Mixed FA7527/FA1090; Mutant FA7527

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy man between the ages of 18 and 35 years.
• 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.
• Able and willing to attend all study visits including 6-day stay in the Clinical and Translational Research Center (CTRC) during the trial (with ability to leave the unit during the day) and follow-up visit during the week after treatment.
• Able and willing to abstain from masturbation during the 6-day stay in the CTRC.
• Able and willing to abstain from all sexual activity during the course of the study.
• Acceptable medical history by screening evaluation.
• Standard physical exam within normal limits (WNL).
• Serum creatinine WNL.
• Serum alanine transaminase (ALT) WNL.
• White blood cell (WBC), polymorphonuclear cell (PMN) and hemoglobin values WNL.
• Normal urinalysis.
• Total Complement (CH50) WNL.
• Urine negative for chlamydia, gonorrhea, trichomonas and mycoplasma.
• Negative HIV, syphilis, and Hepatitis C (HCV) test results.

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.
• Psychiatric disorders that would interfere with the integrity of the data or volunteer safety.
• Unstable depression (defined as receiving either \< 3 months of the same medication (and dose) or a decompensating event during the previous 3 months) or depression that, in the opinion of the investigator, will compromise the subject's ability to comply with protocol requirements.
• Heart murmur or heart disease.
• Anatomic abnormality of the urinary tract.
• Any antibiotic treatment in the past 30 days, or azithromycin in the past 60 days.
• Chemotherapy within the past year.
• Current steroid use, except for topical application.
• Allergy to penicillin, ceftriaxone or ciprofloxacin or to lidocaine.
• Treatment with medications that are contraindicated with ciprofloxacin or ceftriaxone and that cannot be withheld for the single doses given in this study.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

University of North Carolina Health Care - Infectious Diseases

Chapel Hill, North Carolina, 27514-4220, United States

Location

MeSH Terms

Conditions

Gonorrhea

Interventions

Azithromycin; Ceftriaxone; Ciprofloxacin

Condition Hierarchy (Ancestors)

Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sexually Transmitted Diseases, Bacterial; Sexually Transmitted Diseases; Communicable Diseases; Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines

Results Point of Contact

• Title: Marcia M. Hobbs, PhD
• Organization: University of North Carolina at Chapel Hill

mmhobbs@med.unc.edu

919-843-6893

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2021
• First Posted: May 3, 2021
• Study Start: March 10, 2013
• Primary Completion: April 28, 2015
• Study Completion: April 28, 2015
• Last Updated: December 2, 2021
• Results First Posted: December 2, 2021

Record last verified: 2020-09

Locations

US (1)