Experimental Human Infection With Neisseria Gonorrhoeae

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT03840811
• Collaborator: (none)
• Enrollment: 27
• Location: 1
• Arms: 3
• Actual Duration (Months): 31.1
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This is a Phase 1, interventional, non-randomized, experimental infection model study with healthy adult males adults (N=32) between the ages of 18-36 at study enrollment. The study is designed to test the requirements of predicted N. gonorrhoeae virulence determinants for gonococcal infection in the male urethra. The duration for all participants will be about 3 weeks. Study duration will be approximately about 18 months for implementation and enrollment. The primary objectives of the present study are to: (1) compare infectivity of different isogenic mutants with wild-type (WT) N. gonorrhoeae in noncompetitive infections and to (2) assess relative fitness of the mutant in competitive infections initiated by inocula containing equivalent numbers of both WT and mutant strains for mutants with WT infectivity.

Condition or Disease	Intervention/Treatment	Phase
Gonococcal Infection	Drug: Cefixime; Drug: Ceftriaxone; Drug: Ciprofloxacin; Biological: Neisseria gonorrhoeae strain FA1090 A26; Biological: Neisseria gonorrhoeae strain FA7537	Phase 1

Detailed Description

This is a Phase 1, interventional, non-randomized, experimental infection model study with healthy adult males adults (N=32) between the ages of 18-36 at study enrollment. The study is designed to test the requirements of predicted N. gonorrhoeae virulence determinants for gonococcal infection in the male urethra. For each mutant to be investigated under this protocol, groups of subjects will be enrolled first in noncompetitive infection studies: Group 1 (n = up to 8) will receive a bacterial inoculum containing only the isogenic mutant

1. gonorrhoeae strain, and Group 2 (n = up to 8) will receive a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain. If primary and secondary outcomes are not different for the isogenic mutant and WT strains, a group of subjects will be enrolled in competitive infection studies: Group 3 (up to 16) will receive a bacterial inoculum containing a mixture of equivalent numbers the isogenic mutant and WT 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. Within 7 days of antibiotic treatment, subjects will return for a follow-up examination. A final follow-up phone interview will be conducted within 2 weeks of antibiotic treatment. The duration for all participants will be about 3 weeks. Study duration will be approximately about 18 months for implementation and enrollment. The primary objectives of the present study are to: (1) compare infectivity of different isogenic mutants with wild-type (WT) N. gonorrhoeae in noncompetitive infections and to (2) assess relative fitness of the mutant in competitive infections initiated by inocula containing equivalent numbers of both WT and mutant strains for mutants with WT infectivity. Note, competitive infections will not be performed if non-competitive infections are substantially different. If this is the case, there will be no analysis for this primary objective. The study secondary objective is to compare the clinical course of infection with mutant and WT N. gonorrhoeae in noncompetitive infections.

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 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
• Actual Study Start Date: Apr 23, 2017
• Actual Primary Completion Date: Nov 25, 2019
• Actual Study Completion Date: Nov 25, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 Subjects (n = up to 8) will receive a bacterial inoculum containing only the isogenic mutant N. gonorrhoeae strain	Drug: Cefixime; Mandatory rescue therapy consisting of cefixime 400 mg orally in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation.; Drug: Ceftriaxone; Mandatory rescue therapy consisting of ceftriaxone 250 mg intramuscularly 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: if the subject has a positie test of cure 1 week post initial antibiotic treatment; Biological: Neisseria gonorrhoeae strain FA7537; 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
Experimental: Group 2 Subjects (n = up to 8) will receive a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain.	Drug: Cefixime; Mandatory rescue therapy consisting of cefixime 400 mg orally in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation.; Drug: Ceftriaxone; Mandatory rescue therapy consisting of ceftriaxone 250 mg intramuscularly 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: if the subject has a positie test of cure 1 week post initial antibiotic treatment; Biological: Neisseria gonorrhoeae strain FA1090 A26; 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.
Experimental: Group 3 Subjects (n= up to 16) will receive a bacterial inoculum containing a mixture of equivalent numbers the isogenic mutant and WT strain	Drug: Cefixime; Mandatory rescue therapy consisting of cefixime 400 mg orally in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation.; Drug: Ceftriaxone; Mandatory rescue therapy consisting of ceftriaxone 250 mg intramuscularly 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: if the subject has a positie test of cure 1 week post initial antibiotic treatment; Biological: Neisseria gonorrhoeae strain FA1090 A26; 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.; Biological: Neisseria gonorrhoeae strain FA7537; 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

Outcome Measures

Primary Outcome Measures

1. The Competitive Index of the Mutant Compared to Wild Type Proportion of Organisms With the Predicted Competitive Advantage Recovered From Urine and/or Urethral Swab Specimens From Infected Participants [Baseline and the day of treatment, any day between Day 2 and Day 6]

   The competitive index (CI) is defined by the ratio of colony forming units (cfu) of the two strains recovered from urine cultures on the day of treatment (output) compared to the ratio of strains in the inoculum (input): CI = mutant cfu(output)/wild-type cfu(output) ÷ mutant cfu(input)/wild-type cfu(input). The CI is used to assess whether the fitness of a given mutant is different than that of wild-type, and CI as a ratio is compared to 1. If it's not significantly different than 1, then no significant difference in the fitness was observed. Mutant or wild-type cfu values of 0 were replaced by 1 in the calculation of competitive index. The assessment was performed in the MtrD trial mixed group.

2. Proportion of Participants That Become Infected as Defined by a Positive Urine or Urethral Swab Culture Among Infections Initiated With Individual N. Gonorrhoeae Strains in Non-competitive Infections [day of infection, any day between Day 2 and Day 6]

   Infection is defined by a positive urine or urethral swab culture. The proportion of infected participants by Day 6 with N. gonorrhoeae was assessed in each trial by group among participants with non-competitive infections. Participants could become infected and received treatment any day before or on day 6.

3. Proportion of Participants That Become Infected as Defined by a Positive Urine or Urethral Swab Culture for Infections Initiated With Mixed Inocula [day of infection, any day between Day 2 and Day 6]

   Infection is defined by a positive urine or urethral swab culture. The proportion of infected participants by Day 6 with N. gonorrhoeae was assessed in each trial among participants with infections initiated with mixed inocula. Participants could become infected and received treatment any day before or on day 6.

Secondary Outcome Measures

1. Median Time From Inoculation to Treatment Among Infected Participants by Day 6, by Strain, in Non-competitive Infections [Day 2 through the day of treatment, up to Day 6]

   The median time from inoculation to antibiotic treatment were calculated for each group.

2. Proportion of Participants With Occurrence of Bacteriuria in Non-competitive Infections, by Strain [Day of occurrence, any day between Day 2 and Day 6]

   Bacteriuria is defined as Log10 cfu N. gonorrhoeae/mL urine sediment.

3. Proportion of Participants With Occurrence of Signs and Symptoms of Urethritis Attributable to Gonococcal Infection in Non-competitive Infections, by Strain [Day of occurrence, any day between Day 2 and Day 6]

   Participants with any subjective symptoms or objective signs (observed urethral discharge) during period 01 (post-inoculation and before treatment which can occur on or before day 6) from the Solicited Events Form were captured.

4. Proportion of Participants With Occurrence of Urethritis in Non-competitive Infections [Day of occurrence, any day between Day 2 and Day 6]

   Urethritis is defined as >= 5.8 Log10 WBC/mL urine sediment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 36 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Healthy man > / = 18 and < 36 years old

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 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 all sexual activity until completion of the study and the follow-up test for gonorrhea is negative

6. Acceptable medical history by screening evaluation

7. No clinically significant abnormalities on physical exam

8. Urinalysis: leukocyte esterase, and White Blood Cell (WBC) values within normal limits (WNL)

9. CH50 WNL

10. Urine negative for chlamydia, gonorrhea, and trichomonas

11. Negative Human Immunodeficiency Virus (HIV), syphilis, and Hepatitis C (HCV) test results

12. Negative Hepatitis B (HBV) core and surface antibodies or results consistent with immunization (negative HBV core antibody/positive HBV surface antibody)

13. Denies history of Sexually Transmitted Infections (STIs) including gonorrhea, chlamydia, syphilis, HIV, HBV, and HCV

14. Denies history of bleeding diathesis

15. Denies history of seizures (due to reports of seizures with ciprofloxacin)

16. Denies history of cancer, except basal cell carcinoma of the skin > 5 years ago

17. Denies history of drug abuse

18. 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 Human Immunodeficiency Virus (HIV) infection

3. Psychiatric disorders that, in the opinion of the physician, 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. Self-reported chemotherapy within the past year

9. Current steroid use, except for topical application

10. Allergy to penicillin, cephalosporins or ciprofloxacin or to lidocaine

11. Treatment with medications in the previous month that are contraindicated with cefixime, ceftriaxone or ciprofloxacin and that cannot be withheld for the single doses given in this study

12. Serum creatinine level < 0.7 or > 1.75 mg/dL and deemed clinically significant by the study physician

13. Serum ALT level < LLN or > 105 U/L and deemed clinically significant by the study physician

14. WBC count < 2.5 or > 15.0 x 10^9/L and deemed clinically significant by the study physician

15. Absolute neutrophil count (ANC) < 1.5 or > 7.5 x 10^{9/L and deemed clinically significant by the study physician Exception: For African Americans, ANC values as low as 1.3 x 10}9/L will be allowed (25)

16. Hemoglobin level < 12.0 g/dL or above ULN and deemed clinically significant by the study physician

17. Urinalysis: Qualitative protein level > 1+ or RBC count > 10/hpf

Medications not permitted with cefixime or ceftriaxone:

1. Warfarin

2. Probenecid

3. Aspirin

4. Diuretics such as furosemide

5. Aminoglycoside antibiotics

6. Chloramphenicol

Medications not permitted with ciprofloxacin:

1. Tizanidine

2. Theophylline

3. Warfarin

4. Glyburide

5. Cyclosporine

6. Probenecid

7. Phenytoin

8. Methotrexate

9. Antacids, multivitamins, and other dietary supplements containing magnesium, calcium, aluminum, iron or zinc

10. Caffeine-containing medications

11. Sucralfate or didanosine chewable or buffered tablets

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: NCT03840811
• Other Study ID Numbers: 09-0106
• First Posted: Feb 15, 2019
• Last Update Posted: Mar 23, 2021
• Last Verified: Sep 16, 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; Ciprofloxacin; Ceftriaxone; Cefixime

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 infection (STIs) were enrolled. Participants were enrolled between 23APR2017 and 10NOV2019.

Arm/Group Title	Mutant FA7537	Wild-type FA1090	Mixed FA1090/FA7537
Arm/Group Description	Participants received a bacterial inoculum containing only the isogenic mtrD mutant N. gonorrhoeae strain. Cefixime: Mandatory rescue therapy consisting of cefixime 400 mg orally in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation. Ceftriaxone: Mandatory rescue therapy consisting of ceftriaxone 250 mg intramuscularly in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation. Ciprofloxacin: Mandatory antibiotic treatment failure therapy: Ciprofloxacin 500 mg orally in a single dose: if the participant has a positie test of cure 1 week post initial antibiotic treatment. Neisseria gonorrhoeae strain FA7537: 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.	Participants received a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain. Cefixime: Mandatory rescue therapy consisting of cefixime 400 mg orally in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation. Ceftriaxone: Mandatory rescue therapy consisting of ceftriaxone 250 mg intramuscularly in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation. Ciprofloxacin: Mandatory antibiotic treatment failure therapy: Ciprofloxacin 500 mg orally in a single dose: if the participant has a positie test of cure 1 week post initial antibiotic treatment. Neisseria gonorrhoeae strain FA1090 A26: 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.	Participants received a bacterial inoculum containing a mixture of equivalent numbers the isogenic MtrD mutant and WT strain. Cefixime: Mandatory rescue therapy consisting of cefixime 400 mg orally in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation. Ceftriaxone: Mandatory rescue therapy consisting of ceftriaxone 250 mg intramuscularly in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation. Ciprofloxacin: Mandatory antibiotic treatment failure therapy: Ciprofloxacin 500 mg orally in a single dose: if the participant has a positie test of cure 1 week post initial antibiotic treatment. Neisseria gonorrhoeae strain FA1090 A26: 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. Neisseria gonorrhoeae strain FA7537: 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.
Period Title: Overall Study
STARTED	9	6	12
COMPLETED	9	6	11
NOT COMPLETED	0	0	1

Baseline Characteristics

Arm/Group Title	Mutant FA7537	Wild-type FA1090	Mixed FA1090/FA7537	Total
Arm/Group Description	Participants received a bacterial inoculum containing only the isogenic MtrD 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 MtrD mutant and WT strain.	Total of all reporting groups
Overall Participants	9	6	12	27
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	25.2 (6.1)	21.8 (2.8)	25.2 (4.7)	24.4 (4.9)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	9 100%	6 100%	12 100%	27 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 22.2%	1 16.7%	0 0%	3 11.1%
Not Hispanic or Latino	7 77.8%	5 83.3%	12 100%	24 88.9%
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 11.1%	0 0%	1 8.3%	2 7.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	5 41.7%	5 18.5%
White	6 66.7%	5 83.3%	5 41.7%	16 59.3%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	2 22.2%	1 16.7%	1 8.3%	4 14.8%
Region of Enrollment (participants) [Number]
United States	9 100%	6 100%	12 100%	27 100%

Outcome Measures

1. Primary Outcome

Title	The Competitive Index of the Mutant Compared to Wild Type Proportion of Organisms With the Predicted Competitive Advantage Recovered From Urine and/or Urethral Swab Specimens From Infected Participants
Description	The competitive index (CI) is defined by the ratio of colony forming units (cfu) of the two strains recovered from urine cultures on the day of treatment (output) compared to the ratio of strains in the inoculum (input): CI = mutant cfu(output)/wild-type cfu(output) ÷ mutant cfu(input)/wild-type cfu(input). The CI is used to assess whether the fitness of a given mutant is different than that of wild-type, and CI as a ratio is compared to 1. If it's not significantly different than 1, then no significant difference in the fitness was observed. Mutant or wild-type cfu values of 0 were replaced by 1 in the calculation of competitive index. The assessment was performed in the MtrD trial mixed group.
Time Frame	Baseline and the day of treatment, any day between Day 2 and Day 6

Outcome Measure Data

Analysis Population Description

The evaluable population included participants who received a dose of N. gonorrhoeae within 1 log10 of the intended dose, reached an objective study endpoint (urethral discharge or day 6), and had a valid competitive index (the competitive index could not be calculated for participant who had a negative urine culture result on the day of treatment).

Arm/Group Title	Mixed FA1090/FA7537
Arm/Group Description	Participants received a bacterial inoculum containing a mixture of equivalent numbers the isogenic MtrD mutant and WT strain.
Measure Participants	10
Median (Full Range) [ratio]	15.11

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mixed FA1090/FA7537
	Comments	To assess whether the fitness of a given mutant is different than that of wild-type, the ratio of colony-forming units of the mutant strain was compared to those of the WT strain at the time of treatment and in the inoculum using a Wilcoxon Signed-Rank Test with a significance level of 0.025. CIs of participants in Mixed FA1090 + FA7537 group were compared to mean = 1.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.230
	Comments
	Method	Sign test
	Comments

2. Primary Outcome

Title	Proportion of Participants That Become Infected as Defined by a Positive Urine or Urethral Swab Culture Among Infections Initiated With Individual N. Gonorrhoeae Strains in Non-competitive Infections
Description	Infection is defined by a positive urine or urethral swab culture. The proportion of infected participants by Day 6 with N. gonorrhoeae was assessed in each trial by group among participants with non-competitive infections. Participants could become infected and received treatment any day before or on day 6.
Time Frame	day of infection, any day between Day 2 and Day 6

Outcome Measure Data

Analysis Population Description

The evaluable population included participants who received a dose of N. gonorrhoeae within 1 log10 of the intended dose and reached an objective study endpoint (urethral discharge or day 6).

Arm/Group Title	Mutant FA7537	Wild-type FA1090
Arm/Group Description	Participants received a bacterial inoculum containing only the isogenic MtrD mutant N. gonorrhoeae strain.	Participants received a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain.
Measure Participants	7	6
Number (95% Confidence Interval) [proportion of participants]	0.86 9.6%	1.00 16.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mixed FA1090/FA7537, Wild-type FA1090
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.54
	Comments	One-sided Fisher's Exact Test with alpha=0.025
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95%; -0.58 to 0.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Proportion of Participants That Become Infected as Defined by a Positive Urine or Urethral Swab Culture for Infections Initiated With Mixed Inocula
Description	Infection is defined by a positive urine or urethral swab culture. The proportion of infected participants by Day 6 with N. gonorrhoeae was assessed in each trial among participants with infections initiated with mixed inocula. Participants could become infected and received treatment any day before or on day 6.
Time Frame	day of infection, any day between Day 2 and Day 6

Outcome Measure Data

Analysis Population Description

The evaluable population included participants who received a dose of N. gonorrhoeae within 1 log10 of the intended dose and reached an objective study endpoint (urethral discharge or day 6).

Arm/Group Title	Mixed FA1090/FA7537
Arm/Group Description	Participants received a bacterial inoculum containing a mixture of equivalent numbers the isogenic MtrD mutant and WT strain.
Measure Participants	11
Number (95% Confidence Interval) [proportion of participants]	1.00 11.1%

4. Secondary Outcome

Title	Median Time From Inoculation to Treatment Among Infected Participants by Day 6, by Strain, in Non-competitive Infections
Description	The median time from inoculation to antibiotic treatment were calculated for each group.
Time Frame	Day 2 through the day of treatment, up to Day 6

Outcome Measure Data

Analysis Population Description

The evaluable population included participants who received a dose of N. gonorrhoeae within 1 log10 of the intended dose and reached an objective study endpoint (urethral discharge or day 6).

Arm/Group Title	Mutant FA7537	Wild-type FA1090
Arm/Group Description	Participants received a bacterial inoculum containing only the isogenic MtrD mutant N. gonorrhoeae strain.	Participants received a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain.
Measure Participants	7	6
Median (Full Range) [days]	3.0	3.0

5. Secondary Outcome

Title	Proportion of Participants With Occurrence of Bacteriuria in Non-competitive Infections, by Strain
Description	Bacteriuria is defined as Log10 cfu N. gonorrhoeae/mL urine sediment.
Time Frame	Day of occurrence, any day between Day 2 and Day 6

Outcome Measure Data

Analysis Population Description

The evaluable population included participants who received a dose of N. gonorrhoeae within 1 log10 of the intended dose and reached an objective study endpoint (urethral discharge or day 6).

Arm/Group Title	Mutant FA7537	Wild-type FA1090
Arm/Group Description	Participants received a bacterial inoculum containing only the isogenic MtrD mutant N. gonorrhoeae strain.	Participants received a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain.
Measure Participants	7	6
Number (95% Confidence Interval) [proportion of participants]	0.86 9.6%	1.00 16.7%

6. Secondary Outcome

Title	Proportion of Participants With Occurrence of Signs and Symptoms of Urethritis Attributable to Gonococcal Infection in Non-competitive Infections, by Strain
Description	Participants with any subjective symptoms or objective signs (observed urethral discharge) during period 01 (post-inoculation and before treatment which can occur on or before day 6) from the Solicited Events Form were captured.
Time Frame	Day of occurrence, any day between Day 2 and Day 6

Outcome Measure Data

Analysis Population Description

The evaluable population included participants who received a dose of N. gonorrhoeae within 1 log10 of the intended dose and reached an objective study endpoint (urethral discharge or day 6).

Arm/Group Title	Mutant FA7537	Wild-type FA1090
Arm/Group Description	Participants received a bacterial inoculum containing only the isogenic MtrD mutant N. gonorrhoeae strain.	Participants received a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain.
Measure Participants	7	6
Number (95% Confidence Interval) [proportion of participants]	1.00 11.1%	1.00 16.7%

7. Secondary Outcome

Title	Proportion of Participants With Occurrence of Urethritis in Non-competitive Infections
Description	Urethritis is defined as >= 5.8 Log10 WBC/mL urine sediment.
Time Frame	Day of occurrence, any day between Day 2 and Day 6

Outcome Measure Data

Analysis Population Description

The evaluable population included participants who received a dose of N. gonorrhoeae within 1 log10 of the intended dose and reached an objective study endpoint (urethral discharge or day 6).

Arm/Group Title	Mutant FA7537	Wild-type FA1090
Arm/Group Description	Participants received a bacterial inoculum containing only the isogenic MtrD mutant N. gonorrhoeae strain.	Participants received a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain.
Measure Participants	7	6
Number (95% Confidence Interval) [proportion of participants]	1.00 11.1%	1.00 16.7%

Adverse Events

Time Frame	All adverse events that occurred from inoculation (Day 1) through the 2 week final follow-up phone call (Study Days 12-23) were reported.
Adverse Event Reporting Description	The solicited and unsolicited AEs reported for the MtrD trial were summarized using MedDRA 22.1
Arm/Group Title	Mutant FA7537		Wild-type FA1090		Mixed FA1090/FA7537
Arm/Group Description	Participants received a bacterial inoculum containing only the isogenic MtrD 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 MtrD mutant and WT strain.
All Cause Mortality
	Mutant FA7537		Wild-type FA1090		Mixed FA1090/FA7537
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/6 (0%)		0/12 (0%)
Serious Adverse Events
	Mutant FA7537		Wild-type FA1090		Mixed FA1090/FA7537
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/6 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Mutant FA7537		Wild-type FA1090		Mixed FA1090/FA7537
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/9 (100%)		6/6 (100%)		12/12 (100%)
Ear and labyrinth disorders
Ear Pain	0/9 (0%)	0	1/6 (16.7%)	1	0/12 (0%)	0
Gastrointestinal disorders
Diarrhoea	0/9 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	1
Vomiting	0/9 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	1
General disorders
Feverishness	1/9 (11.1%)	1	0/6 (0%)	0	0/12 (0%)	0
Immune system disorders
Seasonal Allergy	1/9 (11.1%)	1	0/6 (0%)	0	0/12 (0%)	0
Infections and infestations
Viral Upper Respiratory Tract Infection	1/9 (11.1%)	1	0/6 (0%)	0	1/12 (8.3%)	1
Investigations
Blood Pressure Increased	0/9 (0%)	0	1/6 (16.7%)	1	0/12 (0%)	0
Heart Rate Irregular	1/9 (11.1%)	1	0/6 (0%)	0	0/12 (0%)	0
Nervous system disorders
Tingling	0/9 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	1
Presyncope	0/9 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	1
Renal and urinary disorders
Dysuria	6/9 (66.7%)	6	3/6 (50%)	3	6/12 (50%)	6
Urethral Discharge	6/9 (66.7%)	6	6/6 (100%)	6	12/12 (100%)	13
Urinary Frequency	0/9 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	1
Dysuria	3/9 (33.3%)	3	3/6 (50%)	3	1/12 (8.3%)	1
Urethral Discharge	0/9 (0%)	0	1/6 (16.7%)	1	0/12 (0%)	0
Urethritis Noninfective	0/9 (0%)	0	1/6 (16.7%)	1	1/12 (8.3%)	1
Reproductive system and breast disorders
Irritation or Itching	2/9 (22.2%)	2	0/6 (0%)	0	1/12 (8.3%)	1
Testicular Pain	1/9 (11.1%)	1	0/6 (0%)	0	2/12 (16.7%)	2

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.