Experimental Human Infection With Neisseria Gonorrhoeae (LptA Trial)

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT04870138
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arms: 3
• Actual Duration (Months): 25.6
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Gonococcal Infection	Drug: Azithromycin; Drug: Ceftriaxone; Drug: Ciprofloxacin; Biological: Neisseria gonorrhoeae strain FA1090 A26; Biological: Neisseria gonorrhoeae strain FA7527	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Experimental Human Infection With Isogenic Mutants of Neisseria Gonorrhoeae (LptA Trial)
• Actual Study Start Date: Mar 10, 2013
• Actual Primary Completion Date: Apr 28, 2015
• Actual Study Completion Date: Apr 28, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mixed FA7527/FA1090 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; Alternative antibiotic treatment failure therapy: Azithromycin 2 g orally in a single dose after treatment failure with both cephalosporin and quinolone antibiotics.; Drug: Ceftriaxone; 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.; Drug: Ciprofloxacin; 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.; Biological: Neisseria 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.; Biological: Neisseria 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.
Experimental: Mutant FA7527 Bacterial inoculum containing only the isogenic LptA mutant N. gonorrhoeae strain administered once to the anterior urethra. N= up to 8	Drug: Azithromycin; Alternative antibiotic treatment failure therapy: Azithromycin 2 g orally in a single dose after treatment failure with both cephalosporin and quinolone antibiotics.; Drug: Ceftriaxone; 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.; Drug: Ciprofloxacin; 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.; Biological: Neisseria 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.
Experimental: Wild-type FA1090 Bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain administered once to the anterior urethra. N= up to 8	Drug: Azithromycin; Alternative antibiotic treatment failure therapy: Azithromycin 2 g orally in a single dose after treatment failure with both cephalosporin and quinolone antibiotics.; Drug: Ceftriaxone; 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.; Drug: Ciprofloxacin; 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.; Biological: Neisseria 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.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. Pattern of Gonococcal Gene Expression in Urine Sediment [Day 1 through Day 5]

    RNA-seq is the standard method for measuring bacterial gene expression.

24. Quantity of Gonococcal Gene Expression in Urine Sediment [Day 1 through Day 5]

    RNA-seq is the standard method for measuring bacterial gene expression.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 35 Years
• Sexes Eligible for Study: Male
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of North Carolina Health Care - Infectious Diseases	Chapel Hill	North Carolina	United States	27514-4220

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 9, 2019

More Information

Publications

None provided.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT04870138
• Other Study ID Numbers: 09-0106 LptA
• First Posted: May 3, 2021
• Last Update Posted: Dec 2, 2021
• Last Verified: Sep 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): ceftriaxone; challenge; ciprofloxacin; males; Neisseria gonorrhoeae
• Additional relevant MeSH terms: Infections; Communicable Diseases; Gonorrhea; Azithromycin; Ciprofloxacin; Ceftriaxone

Study Results

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.

Arm/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25	Mixed FA7527/FA1090 A25
Arm/Group Description	Participants received a bacterial inoculum containing only the isogenic LptA mutant N. gonorrhoeae strain. Neisseria gonorrhoeae strain FA7527: 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. Mandatory rescue therapy consisting of ceftriaxone 250 mg intramuscularly in a single dose; or Ciprofloxacin 500 mg orally in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation.	Participants received a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain. Neisseria gonorrhoeae strain FA1090 A25: 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. Mandatory rescue therapy consisting of ceftriaxone 250 mg intramuscularly in a single dose; or Ciprofloxacin 500 mg orally in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation.	Participants received a bacterial inoculum containing a mixture of equivalent numbers the isogenic LptA mutant and WT strain. Neisseria gonorrhoeae strains FA7527 and FA1090 A25: 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. Mandatory rescue therapy consisting of ceftriaxone 250 mg intramuscularly in a single dose; or Ciprofloxacin 500 mg orally in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation.
Period Title: Overall Study
STARTED	5	5	6
COMPLETED	5	5	6
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Mutant FA7527 - LptA	Wild-type FA1090	Mixed FA7527/FA1090	Total
Arm/Group Description	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.	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.	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.	Total of all reporting groups
Overall Participants	5	5	6	16
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	24.3 (2.6)	22.1 (2.3)	24.9 (3.3)	23.8 (2.9)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	5 100%	5 100%	6 100%	16 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 20%	0 0%	1 16.7%	2 12.5%
Not Hispanic or Latino	4 80%	5 100%	5 83.3%	14 87.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 20%	1 20%	0 0%	2 12.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	1 20%	0 0%	2 33.3%	3 18.8%
White	2 40%	4 80%	4 66.7%	10 62.5%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 20%	0 0%	0 0%	1 6.3%
Region of Enrollment (participants) [Number]
United States	5 100%	5 100%	6 100%	16 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Number (95% Confidence Interval) [proportion of participants]	0.80 16%	1.00 20%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mutant FA7527 - LptA, Wild-type FA1090 A25
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	One-sided Fisher's Exact Test with alpha = 0.05
	Method	Fisher Exact
	Comments

2. Primary Outcome

Title	The Proportion of Participants That Become Infected With Mixed Inoculum
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Mixed FA7527/FA1090 A25
Arm/Group Description	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.
Measure Participants	6
Number (95% Confidence Interval) [proportion of participants]	0.83 16.6%

3. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Mixed FA7527/FA1090 A25
Arm/Group Description	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 patient request, at the onset of symptoms or on the 5th study day after inoculation.
Measure Participants	5
Mean (Standard Deviation) [proportion of WT organisms recovered]	1.0 (0.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mutant FA7527 - LptA
	Comments	Null hypothesis: The proportion of the strain in the inoculum = 0.5
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-test, 1 sided
	Comments	One-sided single sample t-test with alpha=0.05

4. Secondary Outcome

Title	EGF Cytokine Levels in Peripheral Blood
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Screening Visit	85.0	33.5
Treatment Visit	42.6	29.6
Follow-Up Visit	37.9	42.9

5. Secondary Outcome

Title	Eotaxin Cytokine Levels in Peripheral Blood
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Screening Visit	351.9	267.4
Treatment Visit	422.7	247.3
Follow-Up Visit	407.1	218.3

6. Secondary Outcome

Title	G-CSF Cytokine Levels in Peripheral Blood
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Screening Visit	32.5	81.6
Treatment Visit	37.8	91.4
Follow-Up Visit	19.2	72.9

7. Secondary Outcome

Title	Fractalkine Cytokine Levels in Peripheral Blood
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Screening Visit	202.2	761.8
Treatment Visit	248.3	762.9
Follow-Up Visit	222.2	853.7

8. Secondary Outcome

Title	GRO Cytokine Levels in Peripheral Blood
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Screening Visit	1003.9	433.5
Treatment Visit	436.4	507.3
Follow-Up Visit	403.1	605.5

9. Secondary Outcome

Title	IL-1RA Cytokine Levels in Peripheral Blood
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Screening Visit	145.6	104.5
Treatment Visit	144.0	94.0
Follow-Up Visit	106.2	97.7

10. Secondary Outcome

Title	IL-8 Cytokine Levels in Peripheral Blood
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Screening Visit	17.3	22.1
Treatment Visit	23.0	21.6
Follow-Up Visit	18.0	21.2

11. Secondary Outcome

Title	IP-10 Cytokine Levels in Peripheral Blood
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Screening Visit	630.8	598.4
Treatment Visit	781.0	790.3
Follow-Up Visit	516.0	361.9

12. Secondary Outcome

Title	MCP-1 Cytokine Levels in Peripheral Blood
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Screening Visit	428.0	339.7
Treatment Visit	563.0	271.7
Follow-Up Visit	379.2	284.1

13. Secondary Outcome

Title	MIP-1Beta Cytokine Levels in Peripheral Blood
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Screening Visit	45.4	42.9
Treatment Visit	48.4	37.8
Follow-Up Visit	39.4	36.0

14. Secondary Outcome

Title	VEGF Cytokine Levels in Peripheral Blood
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Screening Visit	321.1	480.7
Treatment Visit	340.3	376.7
Follow-Up Visit	334.1	409.9

15. Secondary Outcome

Title	EGF Cytokine Levels in Urine
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Screening Visit	7333.2	6600.9
Treatment Visit	7358.1	8325.2
Follow-Up Visit	7358.1	8490.4

16. Secondary Outcome

Title	Eotaxin Cytokine Levels in Urine
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Screening Visit	5.2	2.7
Treatment Visit	5.9	5.4
Follow-Up Visit	7.1	2.2

17. Secondary Outcome

Title	G-CSF Cytokine Levels in Urine
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Screening Visit	16.6	25.6
Treatment Visit	113.1	207.1
Follow-Up Visit	18.3	9.5

18. Secondary Outcome

Title	Fractalkine Cytokine Levels in Urine
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Screening Visit	137.2	58.5
Treatment Visit	57.0	71.0
Follow-Up Visit	75.5	86.9

19. Secondary Outcome

Title	GRO Cytokine Levels in Urine
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Screening Visit	13.8	3.5
Treatment Visit	54.7	224.6
Follow-Up Visit	28.9	4.0

20. Secondary Outcome

Title	IL-1RA Cytokine Levels in Urine
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Screening Visit	210.9	44.9
Treatment Visit	205.2	72.1
Follow-Up Visit	138.8	64.1

21. Secondary Outcome

Title	IL-8 Cytokine Levels in Urine
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Screening Visit	1.6	1.6
Treatment Visit	35.3	32.9
Follow-Up Visit	6.3	1.6

22. Secondary Outcome

Title	IP-10 Cytokine Levels in Urine
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Screening Visit	64.5	23.4
Treatment Visit	387.8	411.4
Follow-Up Visit	177.8	23.7

23. Secondary Outcome

Title	MCP-1 Cytokine Levels in Urine
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Screening Visit	757.7	113.0
Treatment Visit	622.5	233.9
Follow-Up Visit	491.7	137.9

24. Secondary Outcome

Title	MIP-1Beta Cytokine Levels in Urine
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Screening Visit	2.1	1.6
Treatment Visit	16.6	22.0
Follow-Up Visit	1.6	1.6

25. Secondary Outcome

Title	VEGF Cytokine Levels in Urine
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	5	5
Screening Visit	104.9	45.3
Treatment Visit	171.8	111.3
Follow-Up Visit	185.1	71.8

26. Secondary Outcome

Title	Pattern of Gonococcal Gene Expression in Urine Sediment
Description	RNA-seq is the standard method for measuring bacterial gene expression.
Time Frame	Day 1 through Day 5

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Mutant FA7527	Wild-type FA1090 A25
Arm/Group Description	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.	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.
Measure Participants	0	0

27. Secondary Outcome

Title	Quantity of Gonococcal Gene Expression in Urine Sediment
Description	RNA-seq is the standard method for measuring bacterial gene expression.
Time Frame	Day 1 through Day 5

Outcome Measure Data

Analysis Population Description

All participants that received bacterial inoculum. Samples obtained were not adequate for analysis with current testing methods

Arm/Group Title	Mutant FA7527 - LptA	Wild-type FA1090 A25	Mixed FA7527/FA1090 A25
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

Adverse Events

Time Frame	All AEs that occurred within the experimental infection trial period including inoculation and one week after the follow-up visit were reported. Events noted through a telephone call approximately 7 days after the follow-up visit to assess potential AEs were also reported.
Adverse Event Reporting Description	The unsolicited AEs were summarized using MedDRA 15.1. The solicited AEs were assessed using MedDRA 22.1
Arm/Group Title	Mutant FA7527		Wild-type FA1090 A25		Mixed FA7527/FA1090 A25
Arm/Group Description	Participants received a bacterial inoculum containing only the isogenic LptA mutant N. gonorrhoeae strain.		Participants received a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain.		Participants received a bacterial inoculum containing a mixture of equivalent numbers the isogenic LptA mutant and WT strain.
All Cause Mortality
	Mutant FA7527		Wild-type FA1090 A25		Mixed FA7527/FA1090 A25
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)		0/6 (0%)
Serious Adverse Events
	Mutant FA7527		Wild-type FA1090 A25		Mixed FA7527/FA1090 A25
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Mutant FA7527		Wild-type FA1090 A25		Mixed FA7527/FA1090 A25
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/5 (80%)		5/5 (100%)		6/6 (100%)
Gastrointestinal disorders
Diarrhoea	0/5 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	1
General disorders
Instillation Site Pain	0/5 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	1
Investigations
Blood Pressure Increased	2/5 (40%)	2	0/5 (0%)	0	1/6 (16.7%)	1
Musculoskeletal and connective tissue disorders
Myalgia	0/5 (0%)	0	1/5 (20%)	1	0/6 (0%)	0
Nervous system disorders
Headache	1/5 (20%)	1	0/5 (0%)	0	0/6 (0%)	0
Tingling	0/5 (0%)	0	0/5 (0%)	0	2/6 (33.3%)	2
Renal and urinary disorders
Dysuria	2/5 (40%)	2	2/5 (40%)	2	1/6 (16.7%)	1
Glycosuria	1/5 (20%)	1	0/5 (0%)	0	0/6 (0%)	0
Hematuria	0/5 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	1
Urethral Discharge	3/5 (60%)	3	5/5 (100%)	5	5/6 (83.3%)	6
Urethritis	1/5 (20%)	1	0/5 (0%)	0	0/6 (0%)	0
Reproductive system and breast disorders
Irritation or Itching	0/5 (0%)	0	1/5 (20%)	1	2/6 (33.3%)	2
Respiratory, thoracic and mediastinal disorders
Postnasal Drip	0/5 (0%)	0	1/5 (20%)	1	0/6 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.