Gonococcal Infection
Conditions
Keywords
ceftriaxone, challenge, ciprofloxacin, males, Neisseria gonorrhoeae
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.
Detailed description
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 hypothesize that key virulence determinants involved in N. gonorrhoeae adherence and resistance to innate immunity are essential for infection in the male urethra. We predict that mutations abolishing expression of these virulence determinants will eliminate or significantly reduce gonococcal infectivity or the ability to induce inflammation in an infected individual, thus identifying potential vaccine candidates. For each mutant to be investigated under this protocol, initial trials will be conducted in which subjects receive a bacterial inoculum containing a mixture of equivalent numbers of two isogenic strains, differing in expression of one or more genes. A competitive advantage for one strain during urethral infection will be manifest by recovery of that strain in a statistically significantly higher proportion of isolates recovered from infected subjects than in the inoculum. Following infections with mixed inocula, infectivity of the mutant in single-strain infections will be compared to that of the wild-type in single-strain infections. In addition, the proportion of infected subjects that develop signs or symptoms of urethritis with mutant and wild- type inocula will be compared. The Mixed FA7527/FA1090 group (n = up to 25 ) will receive a bacterial inoculum containing a mixture of equivalent numbers of the isogenic mutant and WT strains. In single-strain infections, the Mutant FA7527 group (n = up to 8) will receive a bacterial inoculum containing only the isogenic mutant N. gonorrhoeae strain, and the Wild-type FA1090 group (n = up to 8) will receive a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain. All subjects will be examined daily for symptoms of infection and receive antibiotic treatment at the end of the inpatient portion of the trial. 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. The study secondary objectives are to: (1) characterize host immune responses to infection by measuring cytokines and other mediators in specimens including serum, peripheral blood lymphocytes and urine obtained from subjects before, during and after experimental gonococcal infection, and (2) characterize bacterial gene expression during experimental infection.
Interventions
DRUGAzithromycin
Alternative antibiotic treatment failure therapy: Azithromycin 2 g orally in a single dose after treatment failure with both cephalosporin and quinolone antibiotics.
DRUGCeftriaxone
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.
DRUGCiprofloxacin
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.
BIOLOGICALNeisseria gonorrhoeae strain FA1090 A26
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.
BIOLOGICALNeisseria gonorrhoeae strain FA7527
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.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy man between the ages of 18 and 35 years. 2. Able and willing to be located easily by providing street address and telephone number (land line and/or cell phone number). 3. Willingness to provide written informed consent. 4. 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. 5. Able and willing to abstain from masturbation during the 6-day stay in the CTRC. 6. Able and willing to abstain from all sexual activity during the course of the study. 7. Acceptable medical history by screening evaluation. 8. Standard physical exam within normal limits (WNL). 9. Serum creatinine WNL. 10. Serum alanine transaminase (ALT) WNL. 11. White blood cell (WBC), polymorphonuclear cell (PMN) and hemoglobin values WNL. 12. Normal urinalysis. 13. Total Complement (CH50) WNL. 14. Urine negative for chlamydia, gonorrhea, trichomonas and mycoplasma. 15. Negative HIV, syphilis, and Hepatitis C (HCV) test results. 16. Negative Hepatitis B (HBV) core and surface antibodies or results consistent with immunization (negative HBV core antibody/positive HBV surface antibody). 17. Denies history of STIs including syphilis and hepatitis B & C. 18. Denies history of bleeding diathesis. 19. Denies history of seizures (due to reports of seizures with ciprofloxacin). 20. Denies history of cancer, except basal cell carcinoma of the skin more than 5 years ago. 21. Denies history of drug abuse. 22. Denies history of psychiatric disorders, except depression controlled by medication. 23. Denies history of genitourinary surgery.
Exclusion criteria
1. Student or employee under the direct supervision of any of the study investigators. 2. Any known immunodeficiencies including complement deficiency, antibody deficiency, chronic granulomatous disease or HIV infection. 3. Psychiatric disorders that would interfere with the integrity of the data or volunteer safety. 4. 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. 5. Heart murmur or heart disease. 6. Anatomic abnormality of the urinary tract. 7. Any antibiotic treatment in the past 30 days, or azithromycin in the past 60 days. 8. Chemotherapy within the past year. 9. Current steroid use, except for topical application. 10. Allergy to penicillin, ceftriaxone or ciprofloxacin or to lidocaine. 11. Treatment with medications that are contraindicated with ciprofloxacin or ceftriaxone and that cannot be withheld for the single doses given in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Participants That Become Infected With Individual N. Gonorrhoeae Strains in Non-competitive Infections | Day of infection, any day between Day 1 and Day 5 | 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. |
| The Proportion of Participants That Become Infected With Mixed Inoculum | Day of infection, any day between Day 1 and Day 5 | 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. |
| The Proportion of Wild Type (WT) Organisms Recovered From Urine and Urethral Swab Specimens From Individual Subjects Infected With Mixed Inoculum | Baseline (Day 0) and the day of infection (any day between Day 1 and Day 5) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Fractalkine Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. |
| 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) | GRO Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. |
| IL-1RA 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) | IL-1RA Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. |
| IL-8 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) | IL-8 Cytokine levels in peripheral blood collected from subjects were measured at the eligibility testing visit, during experimental infection and at the follow-up visit. Only cytokines detected during experimental infection in \> 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. |
| IP-10 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) | IP-10 Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. |
| MCP-1 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) | MCP-1 Cytokine levels in peripheral blood collected from subjects were measured at the eligibility testing visit, during experimental infection and at the follow-up visit. Only cytokines detected during experimental infection in \> 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. |
| MIP-1Beta 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) | MIP-1Beta Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. |
| VEGF 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) | VEGF Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. |
| EGF Cytokine Levels in Urine | 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) | EGF Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded. |
| Eotaxin Cytokine Levels in Urine | 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 urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded. |
| 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) | EGF Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. |
| Fractalkine Cytokine Levels in Urine | 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 urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded. |
| GRO Cytokine Levels in Urine | 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 urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded. |
| IL-1RA Cytokine Levels in Urine | 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) | IL-1RA Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded. |
| IL-8 Cytokine Levels in Urine | 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) | IL-8 Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded. |
| IP-10 Cytokine Levels in Urine | 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) | IP-10 Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded. |
| MCP-1 Cytokine Levels in Urine | 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) | MCP-1 Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded. |
| MIP-1Beta Cytokine Levels in Urine | 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) | MIP-1Beta Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded. |
| VEGF Cytokine Levels in Urine | 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) | VEGF Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded. |
| Pattern of Gonococcal Gene Expression in Urine Sediment | Day 1 through Day 5 | RNA-seq is the standard method for measuring bacterial gene expression. |
| Quantity of Gonococcal Gene Expression in Urine Sediment | Day 1 through Day 5 | RNA-seq is the standard method for measuring bacterial gene expression. |
| G-CSF Cytokine Levels in Urine | 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 urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded. |
| 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) | Eotaxin cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. |
| 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) | G-CSF Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. |
Countries
United States
Participant flow
Recruitment details
Males aged 18-\<36 years old, living in central North Carolina, in general good health with no history of sexually transmitted infections (STIs) were enrolled. Participants were enrolled between 10MAR2013 and 26APR2015.
Participants by arm
| Arm | Count |
|---|---|
| Mutant FA7527 - LptA Participants received a bacterial inoculum containing only the isogenic LptA mutant N. gonorrhoeae strain. Mandatory rescue therapy in a single dose, on participant request, at the onset of symptoms or on the 5th study day after inoculation. | 5 |
| Wild-type FA1090 Participants received a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain. Mandatory rescue therapy in a single dose, on participant request, at the onset of symptoms or on the 5th study day after inoculation. | 5 |
| Mixed FA7527/FA1090 Participants received a bacterial inoculum containing a mixture of equivalent numbers the isogenic LptA mutant and WT strain. Mandatory rescue therapy in a single dose, on participant request, at the onset of symptoms or on the 5th study day after inoculation. | 6 |
| Total | 16 |
Baseline characteristics
| Characteristic | Total | Mutant FA7527 - LptA | Wild-type FA1090 | Mixed FA7527/FA1090 |
|---|---|---|---|---|
| Age, Continuous | 23.8 Years STANDARD_DEVIATION 2.9 | 24.3 Years STANDARD_DEVIATION 2.6 | 22.1 Years STANDARD_DEVIATION 2.3 | 24.9 Years STANDARD_DEVIATION 3.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 4 Participants | 5 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 2 Participants | 4 Participants | 4 Participants |
| Region of Enrollment United States | 16 participants | 5 participants | 5 participants | 6 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 16 Participants | 5 Participants | 5 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 | 0 / 6 |
| other Total, other adverse events | 4 / 5 | 5 / 5 | 6 / 6 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 | 0 / 6 |
Outcome results
Primary
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.
Time frame: Day of infection, any day between Day 1 and Day 5
Population: All participants inoculated with a dose of N. gonorrhoeae within 1 log10 of the intended dose and reached an objective study endpoint (symptoms of urethritis or day 5)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mutant FA7527 - LptA | The Proportion of Participants That Become Infected With Individual N. Gonorrhoeae Strains in Non-competitive Infections | 0.80 proportion of participants |
| Wild-type FA1090 A25 | The Proportion of Participants That Become Infected With Individual N. Gonorrhoeae Strains in Non-competitive Infections | 1.00 proportion of participants |
p-value: 1Fisher Exact
Primary
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.
Time frame: Day of infection, any day between Day 1 and Day 5
Population: All participants inoculated with a dose of N. gonorrhoeae within 1 log10 of the intended dose and reached an objective study endpoint (symptoms of urethritis or day 5).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mutant FA7527 - LptA | The Proportion of Participants That Become Infected With Mixed Inoculum | 0.83 proportion of participants |
Primary
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.
Time frame: Baseline (Day 0) and the day of infection (any day between Day 1 and Day 5)
Population: All participants inoculated with a dose of N. gonorrhoeae within 1 log10 of the intended dose and reached an objective study endpoint (symptoms of urethritis or day 5).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mutant FA7527 - LptA | The Proportion of Wild Type (WT) Organisms Recovered From Urine and Urethral Swab Specimens From Individual Subjects Infected With Mixed Inoculum | 1.0 proportion of WT organisms recovered | Standard Deviation 0 |
Comparison: Null hypothesis: The proportion of the strain in the inoculum = 0.5p-value: <0.0001t-test, 1 sided
Secondary
EGF Cytokine Levels in Peripheral Blood
EGF Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine.
Time frame: 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)
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group, with EGF Cytokine outcomes specified in Description.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mutant FA7527 - LptA | EGF Cytokine Levels in Peripheral Blood | Screening Visit | 85.0 pg/mL |
| Mutant FA7527 - LptA | EGF Cytokine Levels in Peripheral Blood | Treatment Visit | 42.6 pg/mL |
| Mutant FA7527 - LptA | EGF Cytokine Levels in Peripheral Blood | Follow-Up Visit | 37.9 pg/mL |
| Wild-type FA1090 A25 | EGF Cytokine Levels in Peripheral Blood | Screening Visit | 33.5 pg/mL |
| Wild-type FA1090 A25 | EGF Cytokine Levels in Peripheral Blood | Treatment Visit | 29.6 pg/mL |
| Wild-type FA1090 A25 | EGF Cytokine Levels in Peripheral Blood | Follow-Up Visit | 42.9 pg/mL |
Secondary
EGF Cytokine Levels in Urine
EGF Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded.
Time frame: 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)
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group, with EGF Cytokine outcomes specified in Description.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mutant FA7527 - LptA | EGF Cytokine Levels in Urine | Screening Visit | 7333.2 pg/mL |
| Mutant FA7527 - LptA | EGF Cytokine Levels in Urine | Treatment Visit | 7358.1 pg/mL |
| Mutant FA7527 - LptA | EGF Cytokine Levels in Urine | Follow-Up Visit | 7358.1 pg/mL |
| Wild-type FA1090 A25 | EGF Cytokine Levels in Urine | Follow-Up Visit | 8490.4 pg/mL |
| Wild-type FA1090 A25 | EGF Cytokine Levels in Urine | Screening Visit | 6600.9 pg/mL |
| Wild-type FA1090 A25 | EGF Cytokine Levels in Urine | Treatment Visit | 8325.2 pg/mL |
Secondary
Eotaxin Cytokine Levels in Peripheral Blood
Eotaxin cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine.
Time frame: 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)
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group, with Eotaxin Cytokine outcomes specified in Description.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mutant FA7527 - LptA | Eotaxin Cytokine Levels in Peripheral Blood | Treatment Visit | 422.7 pg/mL |
| Mutant FA7527 - LptA | Eotaxin Cytokine Levels in Peripheral Blood | Follow-Up Visit | 407.1 pg/mL |
| Mutant FA7527 - LptA | Eotaxin Cytokine Levels in Peripheral Blood | Screening Visit | 351.9 pg/mL |
| Wild-type FA1090 A25 | Eotaxin Cytokine Levels in Peripheral Blood | Screening Visit | 267.4 pg/mL |
| Wild-type FA1090 A25 | Eotaxin Cytokine Levels in Peripheral Blood | Treatment Visit | 247.3 pg/mL |
| Wild-type FA1090 A25 | Eotaxin Cytokine Levels in Peripheral Blood | Follow-Up Visit | 218.3 pg/mL |
Secondary
Eotaxin Cytokine Levels in Urine
Eotaxin Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded.
Time frame: 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)
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group, with Eotaxin Cytokine outcomes specified in Description.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mutant FA7527 - LptA | Eotaxin Cytokine Levels in Urine | Treatment Visit | 5.9 pg/mL |
| Mutant FA7527 - LptA | Eotaxin Cytokine Levels in Urine | Follow-Up Visit | 7.1 pg/mL |
| Mutant FA7527 - LptA | Eotaxin Cytokine Levels in Urine | Screening Visit | 5.2 pg/mL |
| Wild-type FA1090 A25 | Eotaxin Cytokine Levels in Urine | Screening Visit | 2.7 pg/mL |
| Wild-type FA1090 A25 | Eotaxin Cytokine Levels in Urine | Treatment Visit | 5.4 pg/mL |
| Wild-type FA1090 A25 | Eotaxin Cytokine Levels in Urine | Follow-Up Visit | 2.2 pg/mL |
Secondary
Fractalkine Cytokine Levels in Peripheral Blood
Fractalkine Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine.
Time frame: 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)
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group, with Fractalkine Cytokine outcomes specified in Description.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mutant FA7527 - LptA | Fractalkine Cytokine Levels in Peripheral Blood | Screening Visit | 202.2 pg/mL |
| Mutant FA7527 - LptA | Fractalkine Cytokine Levels in Peripheral Blood | Treatment Visit | 248.3 pg/mL |
| Mutant FA7527 - LptA | Fractalkine Cytokine Levels in Peripheral Blood | Follow-Up Visit | 222.2 pg/mL |
| Wild-type FA1090 A25 | Fractalkine Cytokine Levels in Peripheral Blood | Screening Visit | 761.8 pg/mL |
| Wild-type FA1090 A25 | Fractalkine Cytokine Levels in Peripheral Blood | Treatment Visit | 762.9 pg/mL |
| Wild-type FA1090 A25 | Fractalkine Cytokine Levels in Peripheral Blood | Follow-Up Visit | 853.7 pg/mL |
Secondary
Fractalkine Cytokine Levels in Urine
Fractalkine Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded.
Time frame: 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)
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group, with Fractalkine Cytokine outcomes specified in Description.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mutant FA7527 - LptA | Fractalkine Cytokine Levels in Urine | Screening Visit | 137.2 pg/mL |
| Mutant FA7527 - LptA | Fractalkine Cytokine Levels in Urine | Follow-Up Visit | 75.5 pg/mL |
| Mutant FA7527 - LptA | Fractalkine Cytokine Levels in Urine | Treatment Visit | 57.0 pg/mL |
| Wild-type FA1090 A25 | Fractalkine Cytokine Levels in Urine | Screening Visit | 58.5 pg/mL |
| Wild-type FA1090 A25 | Fractalkine Cytokine Levels in Urine | Treatment Visit | 71.0 pg/mL |
| Wild-type FA1090 A25 | Fractalkine Cytokine Levels in Urine | Follow-Up Visit | 86.9 pg/mL |
Secondary
G-CSF Cytokine Levels in Peripheral Blood
G-CSF Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine.
Time frame: 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)
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group, with G-CSF Cytokine outcomes specified in Description.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mutant FA7527 - LptA | G-CSF Cytokine Levels in Peripheral Blood | Screening Visit | 32.5 pg/mL |
| Mutant FA7527 - LptA | G-CSF Cytokine Levels in Peripheral Blood | Treatment Visit | 37.8 pg/mL |
| Mutant FA7527 - LptA | G-CSF Cytokine Levels in Peripheral Blood | Follow-Up Visit | 19.2 pg/mL |
| Wild-type FA1090 A25 | G-CSF Cytokine Levels in Peripheral Blood | Screening Visit | 81.6 pg/mL |
| Wild-type FA1090 A25 | G-CSF Cytokine Levels in Peripheral Blood | Treatment Visit | 91.4 pg/mL |
| Wild-type FA1090 A25 | G-CSF Cytokine Levels in Peripheral Blood | Follow-Up Visit | 72.9 pg/mL |
Secondary
G-CSF Cytokine Levels in Urine
G-CSF Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded.
Time frame: 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)
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group, with G-CSF Cytokine outcomes specified in Description.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mutant FA7527 - LptA | G-CSF Cytokine Levels in Urine | Screening Visit | 16.6 pg/mL |
| Mutant FA7527 - LptA | G-CSF Cytokine Levels in Urine | Follow-Up Visit | 18.3 pg/mL |
| Mutant FA7527 - LptA | G-CSF Cytokine Levels in Urine | Treatment Visit | 113.1 pg/mL |
| Wild-type FA1090 A25 | G-CSF Cytokine Levels in Urine | Screening Visit | 25.6 pg/mL |
| Wild-type FA1090 A25 | G-CSF Cytokine Levels in Urine | Treatment Visit | 207.1 pg/mL |
| Wild-type FA1090 A25 | G-CSF Cytokine Levels in Urine | Follow-Up Visit | 9.5 pg/mL |
Secondary
GRO Cytokine Levels in Peripheral Blood
GRO Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine.
Time frame: 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)
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group, with GRO Cytokine outcomes specified in Description.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mutant FA7527 - LptA | GRO Cytokine Levels in Peripheral Blood | Screening Visit | 1003.9 pg/mL |
| Mutant FA7527 - LptA | GRO Cytokine Levels in Peripheral Blood | Treatment Visit | 436.4 pg/mL |
| Mutant FA7527 - LptA | GRO Cytokine Levels in Peripheral Blood | Follow-Up Visit | 403.1 pg/mL |
| Wild-type FA1090 A25 | GRO Cytokine Levels in Peripheral Blood | Screening Visit | 433.5 pg/mL |
| Wild-type FA1090 A25 | GRO Cytokine Levels in Peripheral Blood | Follow-Up Visit | 605.5 pg/mL |
| Wild-type FA1090 A25 | GRO Cytokine Levels in Peripheral Blood | Treatment Visit | 507.3 pg/mL |
Secondary
GRO Cytokine Levels in Urine
GRO Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded.
Time frame: 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)
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group, with GRO Cytokine outcomes specified in Description.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mutant FA7527 - LptA | GRO Cytokine Levels in Urine | Follow-Up Visit | 28.9 pg/mL |
| Mutant FA7527 - LptA | GRO Cytokine Levels in Urine | Treatment Visit | 54.7 pg/mL |
| Mutant FA7527 - LptA | GRO Cytokine Levels in Urine | Screening Visit | 13.8 pg/mL |
| Wild-type FA1090 A25 | GRO Cytokine Levels in Urine | Screening Visit | 3.5 pg/mL |
| Wild-type FA1090 A25 | GRO Cytokine Levels in Urine | Treatment Visit | 224.6 pg/mL |
| Wild-type FA1090 A25 | GRO Cytokine Levels in Urine | Follow-Up Visit | 4.0 pg/mL |
Secondary
IL-1RA Cytokine Levels in Peripheral Blood
IL-1RA Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine.
Time frame: 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)
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group, with IL-1RA Cytokine outcomes specified in Description.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mutant FA7527 - LptA | IL-1RA Cytokine Levels in Peripheral Blood | Screening Visit | 145.6 pg/mL |
| Mutant FA7527 - LptA | IL-1RA Cytokine Levels in Peripheral Blood | Treatment Visit | 144.0 pg/mL |
| Mutant FA7527 - LptA | IL-1RA Cytokine Levels in Peripheral Blood | Follow-Up Visit | 106.2 pg/mL |
| Wild-type FA1090 A25 | IL-1RA Cytokine Levels in Peripheral Blood | Follow-Up Visit | 97.7 pg/mL |
| Wild-type FA1090 A25 | IL-1RA Cytokine Levels in Peripheral Blood | Screening Visit | 104.5 pg/mL |
| Wild-type FA1090 A25 | IL-1RA Cytokine Levels in Peripheral Blood | Treatment Visit | 94.0 pg/mL |
Secondary
IL-1RA Cytokine Levels in Urine
IL-1RA Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded.
Time frame: 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)
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group, with IL-1RA Cytokine outcomes specified in Description.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mutant FA7527 - LptA | IL-1RA Cytokine Levels in Urine | Screening Visit | 210.9 pg/mL |
| Mutant FA7527 - LptA | IL-1RA Cytokine Levels in Urine | Treatment Visit | 205.2 pg/mL |
| Mutant FA7527 - LptA | IL-1RA Cytokine Levels in Urine | Follow-Up Visit | 138.8 pg/mL |
| Wild-type FA1090 A25 | IL-1RA Cytokine Levels in Urine | Treatment Visit | 72.1 pg/mL |
| Wild-type FA1090 A25 | IL-1RA Cytokine Levels in Urine | Follow-Up Visit | 64.1 pg/mL |
| Wild-type FA1090 A25 | IL-1RA Cytokine Levels in Urine | Screening Visit | 44.9 pg/mL |
Secondary
IL-8 Cytokine Levels in Peripheral Blood
IL-8 Cytokine levels in peripheral blood collected from subjects were measured at the eligibility testing visit, during experimental infection and at the follow-up visit. Only cytokines detected during experimental infection in \> 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine.
Time frame: 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)
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group, with IL-8 Cytokine outcomes specified in Description.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mutant FA7527 - LptA | IL-8 Cytokine Levels in Peripheral Blood | Screening Visit | 17.3 pg/mL |
| Mutant FA7527 - LptA | IL-8 Cytokine Levels in Peripheral Blood | Treatment Visit | 23.0 pg/mL |
| Mutant FA7527 - LptA | IL-8 Cytokine Levels in Peripheral Blood | Follow-Up Visit | 18.0 pg/mL |
| Wild-type FA1090 A25 | IL-8 Cytokine Levels in Peripheral Blood | Screening Visit | 22.1 pg/mL |
| Wild-type FA1090 A25 | IL-8 Cytokine Levels in Peripheral Blood | Follow-Up Visit | 21.2 pg/mL |
| Wild-type FA1090 A25 | IL-8 Cytokine Levels in Peripheral Blood | Treatment Visit | 21.6 pg/mL |
Secondary
IL-8 Cytokine Levels in Urine
IL-8 Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded.
Time frame: 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)
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group, with IL-8 Cytokine outcomes specified in Description.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mutant FA7527 - LptA | IL-8 Cytokine Levels in Urine | Screening Visit | 1.6 pg/mL |
| Mutant FA7527 - LptA | IL-8 Cytokine Levels in Urine | Treatment Visit | 35.3 pg/mL |
| Mutant FA7527 - LptA | IL-8 Cytokine Levels in Urine | Follow-Up Visit | 6.3 pg/mL |
| Wild-type FA1090 A25 | IL-8 Cytokine Levels in Urine | Follow-Up Visit | 1.6 pg/mL |
| Wild-type FA1090 A25 | IL-8 Cytokine Levels in Urine | Screening Visit | 1.6 pg/mL |
| Wild-type FA1090 A25 | IL-8 Cytokine Levels in Urine | Treatment Visit | 32.9 pg/mL |
Secondary
IP-10 Cytokine Levels in Peripheral Blood
IP-10 Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine.
Time frame: 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)
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group, with IP-10 Cytokine outcomes specified in Description.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mutant FA7527 - LptA | IP-10 Cytokine Levels in Peripheral Blood | Screening Visit | 630.8 pg/mL |
| Mutant FA7527 - LptA | IP-10 Cytokine Levels in Peripheral Blood | Treatment Visit | 781.0 pg/mL |
| Mutant FA7527 - LptA | IP-10 Cytokine Levels in Peripheral Blood | Follow-Up Visit | 516.0 pg/mL |
| Wild-type FA1090 A25 | IP-10 Cytokine Levels in Peripheral Blood | Screening Visit | 598.4 pg/mL |
| Wild-type FA1090 A25 | IP-10 Cytokine Levels in Peripheral Blood | Treatment Visit | 790.3 pg/mL |
| Wild-type FA1090 A25 | IP-10 Cytokine Levels in Peripheral Blood | Follow-Up Visit | 361.9 pg/mL |
Secondary
IP-10 Cytokine Levels in Urine
IP-10 Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded.
Time frame: 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)
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group, with IP-10 Cytokine outcomes specified in Description.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mutant FA7527 - LptA | IP-10 Cytokine Levels in Urine | Screening Visit | 64.5 pg/mL |
| Mutant FA7527 - LptA | IP-10 Cytokine Levels in Urine | Treatment Visit | 387.8 pg/mL |
| Mutant FA7527 - LptA | IP-10 Cytokine Levels in Urine | Follow-Up Visit | 177.8 pg/mL |
| Wild-type FA1090 A25 | IP-10 Cytokine Levels in Urine | Screening Visit | 23.4 pg/mL |
| Wild-type FA1090 A25 | IP-10 Cytokine Levels in Urine | Follow-Up Visit | 23.7 pg/mL |
| Wild-type FA1090 A25 | IP-10 Cytokine Levels in Urine | Treatment Visit | 411.4 pg/mL |
Secondary
MCP-1 Cytokine Levels in Peripheral Blood
MCP-1 Cytokine levels in peripheral blood collected from subjects were measured at the eligibility testing visit, during experimental infection and at the follow-up visit. Only cytokines detected during experimental infection in \> 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine.
Time frame: 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)
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group, with MCP-10 Cytokine outcomes specified in Description.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mutant FA7527 - LptA | MCP-1 Cytokine Levels in Peripheral Blood | Screening Visit | 428.0 pg/mL |
| Mutant FA7527 - LptA | MCP-1 Cytokine Levels in Peripheral Blood | Treatment Visit | 563.0 pg/mL |
| Mutant FA7527 - LptA | MCP-1 Cytokine Levels in Peripheral Blood | Follow-Up Visit | 379.2 pg/mL |
| Wild-type FA1090 A25 | MCP-1 Cytokine Levels in Peripheral Blood | Follow-Up Visit | 284.1 pg/mL |
| Wild-type FA1090 A25 | MCP-1 Cytokine Levels in Peripheral Blood | Screening Visit | 339.7 pg/mL |
| Wild-type FA1090 A25 | MCP-1 Cytokine Levels in Peripheral Blood | Treatment Visit | 271.7 pg/mL |
Secondary
MCP-1 Cytokine Levels in Urine
MCP-1 Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded.
Time frame: 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)
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group, with MCP-1 Cytokine outcomes specified in Description.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mutant FA7527 - LptA | MCP-1 Cytokine Levels in Urine | Follow-Up Visit | 491.7 pg/mL |
| Mutant FA7527 - LptA | MCP-1 Cytokine Levels in Urine | Screening Visit | 757.7 pg/mL |
| Mutant FA7527 - LptA | MCP-1 Cytokine Levels in Urine | Treatment Visit | 622.5 pg/mL |
| Wild-type FA1090 A25 | MCP-1 Cytokine Levels in Urine | Treatment Visit | 233.9 pg/mL |
| Wild-type FA1090 A25 | MCP-1 Cytokine Levels in Urine | Screening Visit | 113.0 pg/mL |
| Wild-type FA1090 A25 | MCP-1 Cytokine Levels in Urine | Follow-Up Visit | 137.9 pg/mL |
Secondary
MIP-1Beta Cytokine Levels in Peripheral Blood
MIP-1Beta Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine.
Time frame: 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)
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group, with MIP-1Beta Cytokine outcomes specified in Description.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mutant FA7527 - LptA | MIP-1Beta Cytokine Levels in Peripheral Blood | Screening Visit | 45.4 pg/mL |
| Mutant FA7527 - LptA | MIP-1Beta Cytokine Levels in Peripheral Blood | Treatment Visit | 48.4 pg/mL |
| Mutant FA7527 - LptA | MIP-1Beta Cytokine Levels in Peripheral Blood | Follow-Up Visit | 39.4 pg/mL |
| Wild-type FA1090 A25 | MIP-1Beta Cytokine Levels in Peripheral Blood | Follow-Up Visit | 36.0 pg/mL |
| Wild-type FA1090 A25 | MIP-1Beta Cytokine Levels in Peripheral Blood | Screening Visit | 42.9 pg/mL |
| Wild-type FA1090 A25 | MIP-1Beta Cytokine Levels in Peripheral Blood | Treatment Visit | 37.8 pg/mL |
Secondary
MIP-1Beta Cytokine Levels in Urine
MIP-1Beta Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded.
Time frame: 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)
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group, with MIP-1Beta Cytokine outcomes specified in Description.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mutant FA7527 - LptA | MIP-1Beta Cytokine Levels in Urine | Screening Visit | 2.1 pg/mL |
| Mutant FA7527 - LptA | MIP-1Beta Cytokine Levels in Urine | Treatment Visit | 16.6 pg/mL |
| Mutant FA7527 - LptA | MIP-1Beta Cytokine Levels in Urine | Follow-Up Visit | 1.6 pg/mL |
| Wild-type FA1090 A25 | MIP-1Beta Cytokine Levels in Urine | Screening Visit | 1.6 pg/mL |
| Wild-type FA1090 A25 | MIP-1Beta Cytokine Levels in Urine | Treatment Visit | 22.0 pg/mL |
| Wild-type FA1090 A25 | MIP-1Beta Cytokine Levels in Urine | Follow-Up Visit | 1.6 pg/mL |
Secondary
Pattern of Gonococcal Gene Expression in Urine Sediment
RNA-seq is the standard method for measuring bacterial gene expression.
Time frame: Day 1 through Day 5
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group. Samples obtained were not adequate for analysis with current testing methods
Secondary
Quantity of Gonococcal Gene Expression in Urine Sediment
RNA-seq is the standard method for measuring bacterial gene expression.
Time frame: Day 1 through Day 5
Population: All participants that received bacterial inoculum. Samples obtained were not adequate for analysis with current testing methods
Secondary
VEGF Cytokine Levels in Peripheral Blood
VEGF Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine.
Time frame: 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)
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group, with VEGF Cytokine outcomes specified in Description.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mutant FA7527 - LptA | VEGF Cytokine Levels in Peripheral Blood | Screening Visit | 321.1 pg/mL |
| Mutant FA7527 - LptA | VEGF Cytokine Levels in Peripheral Blood | Treatment Visit | 340.3 pg/mL |
| Mutant FA7527 - LptA | VEGF Cytokine Levels in Peripheral Blood | Follow-Up Visit | 334.1 pg/mL |
| Wild-type FA1090 A25 | VEGF Cytokine Levels in Peripheral Blood | Screening Visit | 480.7 pg/mL |
| Wild-type FA1090 A25 | VEGF Cytokine Levels in Peripheral Blood | Follow-Up Visit | 409.9 pg/mL |
| Wild-type FA1090 A25 | VEGF Cytokine Levels in Peripheral Blood | Treatment Visit | 376.7 pg/mL |
Secondary
VEGF Cytokine Levels in Urine
VEGF Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in \> 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded.
Time frame: 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)
Population: All participants in the single-strain infection groups, consisting of the Mutant FA7527 - LptA group and Wild-type FA1090 A25 group, with VEGF Cytokine outcomes specified in Description.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mutant FA7527 - LptA | VEGF Cytokine Levels in Urine | Screening Visit | 104.9 pg/mL |
| Mutant FA7527 - LptA | VEGF Cytokine Levels in Urine | Treatment Visit | 171.8 pg/mL |
| Mutant FA7527 - LptA | VEGF Cytokine Levels in Urine | Follow-Up Visit | 185.1 pg/mL |
| Wild-type FA1090 A25 | VEGF Cytokine Levels in Urine | Follow-Up Visit | 71.8 pg/mL |
| Wild-type FA1090 A25 | VEGF Cytokine Levels in Urine | Screening Visit | 45.3 pg/mL |
| Wild-type FA1090 A25 | VEGF Cytokine Levels in Urine | Treatment Visit | 111.3 pg/mL |