Dose-Finding Study of Lyophilized Shigella Sonnei 53G Challenge Strain

• Sponsor: PATH (Other)
• Overall Status: Completed
• CT.gov ID: NCT02816346
• Collaborator: United States Department of Defense (U.S. Fed), Children's Hospital Medical Center, Cincinnati (Other)
• Enrollment: 56
• Location: 1
• Arms: 5
• Duration (Months): 15.6
• Patients Per Site Per Month: 3.6

Study Details

Study Description

Brief Summary

Development of an S. sonnei human challenge model using a newly manufactured lyophilized lot of S. sonnei strain 53G (Lot 1794) that can be used in the future as a challenge strain for all S. sonnei vaccine candidates. An adaptable dosing plan was used to determine the dose of Shigella sonnei 53G that induces the primary outcome in approximately 60% of subjects.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Biological: Shigella sonnei 53G	Phase 1

Detailed Description

Primary objectives:

1. Establish a human challenge model of S. sonnei 53G infection using a lyophilized formulation of the challenge strain.

2. Identify a dose of lyophilized S. sonnei 53G that induces the primary outcome in approximately 60% of subjects with no adverse safety concerns.

Secondary objectives:

1. Estimate quantitative shedding and basic immunogenicity of the challenge strain.

2. Collect and archive blood and fecal samples for systems biology, microbiome, and other omics-based work to be conducted under a separate research protocol in future studies.

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Dose-Finding Study of Lyophilized Shigella Sonnei 53G Challenge Strain
• Study Start Date: Sep 12, 2016
• Actual Primary Completion Date: Dec 31, 2017
• Actual Study Completion Date: Dec 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1: target dose of 500 CFU Shigella sonnei 53G: Investigational Product: One dose of Shigella sonnei rehydrated challenge strain 53G (Lot 1794) suspension in 2 mL of cold sterile water combined and diluted in cold, sterile normal saline 0.9% (i.e. challenge suspension). Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 5 minutes. Received target dose of 500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 510, 717, 588, and 567 CFU).	Biological: Shigella sonnei 53G; Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)
Experimental: Cohort 2: target dose of 1000 CFU Shigella sonnei 53G: Investigational Product: One dose of Shigella sonnei rehydrated challenge strain 53G (Lot 1794) suspension in 2 mL of cold sterile water combined and diluted in cold, sterile normal saline 0.9% (i.e. challenge suspension). Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 5 minutes. Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 817 CFU), since the attack rate of shigellosis for Cohort 1 was below the protocol target of 60%.	Biological: Shigella sonnei 53G; Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)
Experimental: Cohort 3: target dose of 1000 CFU Shigella sonnei 53G: Investigational Product: One dose of Shigella sonnei rehydrated challenge strain 53G (Lot 1794) suspension in 2 mL of cold sterile water combined and diluted in cold, sterile normal saline 0.9% (i.e. challenge suspension). Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 5 minutes. Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 913 CFU. Although the target dose was the same as Cohort 2, the safety monitoring committee felt that the per-protocol a priori definition of shigellosis was too restrictive and that increasing the dose above 1000 CFU may lead to unnecessarily high toxicity.	Biological: Shigella sonnei 53G; Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)
Experimental: Cohort 4: target dose of 1500 CFU Shigella sonnei 53G: Investigational Product: One dose of Shigella sonnei rehydrated challenge strain 53G (Lot 1794) suspension in 2 mL of cold sterile water combined and diluted in cold, sterile normal saline 0.9% (i.e. challenge suspension). Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 5 minutes. Received target dose of 1500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) since the attack rate of shigellosis for Cohort 2 and 3 was below the protocol target of 60%.	Biological: Shigella sonnei 53G; Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)
Experimental: Cohort 5: target dose of CFU Shigella sonnei 53G: Investigational Product: One dose of Shigella sonnei rehydrated challenge strain 53G (Lot 1794) suspension in 2 mL of cold sterile water combined and diluted in cold, sterile normal saline 0.9% (i.e. challenge suspension). Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 5 minutes. Received target dose of 1150 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) as the final confirmatory cohort since it was felt that the disease rate and profile of Cohort 4 was appropriate.	Biological: Shigella sonnei 53G; Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Shigellosis [11 days after administration of S. sonnei]

   Per protocol definition: shedding of S. sonnei in the stool accompanied by moderate-severe diarrhea (4 or more loose/watery Grade 3-5 stools or 400+ gram stools per 24 hours, or requires medical intervention) and/or dysentery (a Grade 3, 4, or 5 stool with gross blood on at least 2 occasions and reportable constitutional symptoms) along with moderate fever (Oral temperature of ≥101.2°F) or one or more severe intestinal symptoms. Alternative endpoint 1 definition: severe diarrhea, or moderate diarrhea plus fever, or moderate diarrhea plus 1 moderate constitutional/enteric symptom, or dysentery. Alternative endpoint 2 definition: severe diarrhea, or moderate diarrhea plus fever, or moderate diarrhea plus 1 severe constitutional/enteric symptom, or dysentery plus 1 severe constitutional/enteric symptom

Secondary Outcome Measures

1. Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen [Baseline (days -5,-1), Day 3, Day 7, and Day 14]

   IgA (total and S. sonnei specific) will be determined in fecal extracts using standard ELISA. IgA was recovered from stool samples using a soybean trypsin inhibitor ethylenediaminetetraacetic acid (EDTA) procedure. The shigella-antigen specific activity was calculated by dividing the endpoint titer by the IgA concentration in matched samples.

2. Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen [Baseline (days -5,-1), Day 3, Day 7, and Day 14]

   IgA (total and S. sonnei specific) will be determined in fecal extracts using standard ELISA. IgA was recovered from stool samples using a soybean trypsin inhibitor-EDTA procedure. The shigella-antigen specific activity was calculated by dividing the endpoint titer by the IgA concentration in matched samples.

3. Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen [57 days]

   Blood (10 mL) was collected on days -1, 7, 14, 28 and 56 for Immunoglobulin A (IgA), Immunoglobulin M (IgM), and Immunoglobulin G (IgG) assay by Enzyme linked immunosorbent assay (ELISA).

4. Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen [57 days]

   Blood (10 mL) was collected on days -1, 7, 14, 28 and 56 for Immunoglobulin A (IgA), Immunoglobulin M (IgM), and Immunoglobulin G (IgG) assay by Enzyme linked immunosorbent assay (ELISA).

5. Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen [57 days]

   Blood (10 mL) was collected on days -1, 7, 14, 28 and 56 for Immunoglobulin A (IgA), Immunoglobulin M (IgM), and Immunoglobulin G (IgG) assay by Enzyme linked immunosorbent assay (ELISA).

6. Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Invaplex Antigen [57 days]

   Blood (10 mL) was collected on days -1, 7, 14, 28 and 56 for Immunoglobulin A (IgA), Immunoglobulin M (IgM), and Immunoglobulin G (IgG) assay by Enzyme linked immunosorbent assay (ELISA).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 49 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Male or non-pregnant female between 18 and 49 years of age (inclusive).

2. General good health defined as (a) no significant medical illness, (b) no clinically significant physical examination findings and (c) no screening laboratory values significantly outside the normal limits of the testing laboratory within 45 days of challenge.

3. Demonstrate comprehension of the protocol procedures and knowledge of study by passing a written examination (pass grade ≥70%) on day -1.

4. Willing to sign an informed consent form (ICF).

5. Willingness to participate for an inpatient stay lasting up to 11 days and an outpatient follow-up lasting 6 months from challenge.

6. Willing to not smoke during the inpatient stay.

7. Available for all planned follow-up visits.

8. Negative serum pregnancy test at screening and negative urine pregnancy test on the day of admission to the inpatient phase for female subjects of childbearing potential. Females of childbearing potential must agree to use an effective method of birth control (birth control pills, injection hormonal contraceptive, implant hormonal contraceptive,

hormonal patch, intrauterine device (IUD), sterilization by hysterectomy or tubal ligation, spermicidal products and barrier methods such as cervical sponge, diaphragm, or condom) within two months of challenge and during the entire study. Abstinence is acceptable. A woman is eligible if she is monogamous with a vasectomized partner.

1. Willing to not donate blood for up to 6 months after completion of the inpatient phase of the study.

2. Willing to refrain from participation in another investigational vaccine or drug trial at least until after completion of the 6 month follow-up safety call.

Exclusion Criteria:

1. Presence of a significant medical condition (e.g. psychiatric conditions, alcohol or illicit drug abuse/dependency, or gastrointestinal disease, such as peptic ulcer, symptoms or evidence of active gastritis or gastroesophageal reflux disease, inflammatory bowel disease), or other laboratory abnormalities which in the opinion of the investigator precludes participation in the study.

2. Immunosuppressive illness or immunoglobulin A (IgA) deficiency

3. Positive serology results for HIV, HBsAg, hepatitis C virus (HCV), or syphilis (RPR) antibodies.

4. Evidence of inflammatory arthritis on exam and/or human leukocyte antigen B27 (HLA-B27) positive.

5. Family history of inflammatory arthritis.

6. Significant abnormalities in screening lab hematology or serum chemistry, as determined by PI.

7. Allergy to fluoroquinolones or trimethoprim-sulfamethoxazole

8. Fewer than 3 stools per week or more than 3 stools per day as the usual frequency.

9. History of diarrhea in the 2 weeks prior to planned inpatient phase

10. Use of antibiotics during the 7 days before receiving the challenge inoculum dosing

11. Use of prescription and/or over the counter (OTC) medications that contain Imodium, acetaminophen, aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs, during the 48 hours prior to investigational product administration

12. Travel within two years prior to dosing to countries where Shigella infection is endemic.

13. Use of any medication known to affect the immune function [e.g., oral steroids, parenteral steroids, or high-dose inhaled steroids (>800 μg/day of beclomethasone dipropionate or equivalent and others): nasal and topical steroids are allowed] within 30 days preceding receipt of the challenge inoculum or planned use during the active study period.

14. Serologic evidence of Shigella sonnei (titer > 1:2500)

15. A positive urine test for opiates.

16. A chronic disease (such as hypertension, hyperlipidemia or anxiety/depression) for which doses of prescription medications are not stable for at least the past 3 months.

17. Scheduled and/or long-term use of oral steroids, parenteral steroids, or high-dose inhaled steroids (>800 μg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (Nasal, intra-articular, and topical steroids are allowed)

18. Have immunocompromised household contacts.

19. A clinically significant abnormality on physical examination, including a systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg, or a resting pulse

100 beats/min or <55 beats/min (<50 beats/min for conditioned athletes).

1. Pregnant, nursing, or plan to become pregnant within 6 months of receipt of the study product.

2. In the 4 weeks following challenge, subject will be living with or having daily contact with elderly persons aged 70 years or more, diapered individuals, persons with disabilities, children <2 years old, or a woman known to be pregnant or nursing, or anyone with diminished immunity. This includes contact at home, school, day-care, nursing homes, or similar places.

3. Work in a health care setting, day care center, or as a food handler in the 4 weeks following the challenge with S. sonnei.

4. Use of any investigational drug or any investigational vaccine within 60 days preceding challenge, or planned use during the 6 months after receipt of the study agent.

5. Have received a licensed, live vaccine within 28 days or a licensed inactivated vaccine within 14 days of receiving the challenge inoculum.

6. Inability to comply with inpatient rules and regulations.

7. Has any other condition that, in the opinion of the Investigator, would jeopardize the safety or rights of a participant or would render the subject unable to comply with the protocol.

8. Received blood or blood products within the past six months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229

Sponsors and Collaborators

• PATH
• United States Department of Defense
• Children's Hospital Medical Center, Cincinnati

Investigators

• Principal Investigator: Robert Frenck, MD, Children's Hospital Medical Center, Cincinnati

Study Documents (Full-Text)

• Study Protocol and Informed Consent Form - Apr 14, 2017
• Statistical Analysis Plan - Oct 16, 2017

More Information

Publications

None provided.

• Responsible Party: PATH
• ClinicalTrials.gov Identifier: NCT02816346
• Other Study ID Numbers: VAC-048
• First Posted: Jun 28, 2016
• Last Update Posted: Jun 3, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by PATH: shigella
• Additional relevant MeSH terms: Dysentery, Bacillary

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from the recruiting range of Cincinnati Children's Hospital Medical Center (CCHMC) via word of mouth and advertisements in multiple formats including but not limited to newspapers, fliers, e-mails, and the CCHMC website.

Arm/Group Title	Cohort 1: S. Sonnei 53G Target Dose 500 CFU	Cohort 2: S. Sonnei 53G Target Dose 1000 CFU	Cohort 3: S. Sonnei 53G Target Dose of 1000 CFU	Cohort 4: S. Sonnei 53G Target Dose 1500 CFU	Cohort 5: S. Sonnei 53G Target Dose 1150 CFU
Arm/Group Description	Shigella sonnei 53G: Investigational Product: One dose of Shigella sonnei rehydrated challenge strain 53G (Lot 1794) suspension in 2 mL of cold sterile water combined and diluted in cold, sterile normal saline 0.9% (i.e. challenge suspension). Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 5 minutes. Target Dose: 500cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received higher dose of Shigella sonnei 53G if ≥ 60% of subjects in Cohort 1 experienced shigellosis, or lower dose if not. Shigella sonnei 53G: Investigational Product: One dose of Shigella sonnei rehydrated challenge strain 53G (Lot 1794) suspension in 2 mL of cold sterile water combined and diluted in cold, sterile normal saline 0.9% (i.e. challenge suspension). Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 5 minutes. Dose: 1000 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received higher dose of Shigella sonnei 53G if ≥ 60% of subjects in Cohort 2 experienced shigellosis, or lower dose if not. Shigella sonnei 53G: Investigational Product: One dose of Shigella sonnei rehydrated challenge strain 53G (Lot 1794) suspension in 2 mL of cold sterile water combined and diluted in cold, sterile normal saline 0.9% (i.e. challenge suspension). Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 5 minutes. Dose: 1000 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received higher dose of Shigella sonnei 53G if ≥ 60% of subjects in Cohort 3 experienced shigellosis, or lower dose if not. Shigella sonnei 53G: Investigational Product: One dose of Shigella sonnei rehydrated challenge strain 53G (Lot 1794) suspension in 2 mL of cold sterile water combined and diluted in cold, sterile normal saline 0.9% (i.e. challenge suspension). Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 5 minutes. Dose: 1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received higher dose of Shigella sonnei 53G if ≥ 60% of subjects in Cohort 4 experienced shigellosis, or lower dose if not. Shigella sonnei 53G: Investigational Product: One dose of Shigella sonnei rehydrated challenge strain 53G (Lot 1794) suspension in 2 mL of cold sterile water combined and diluted in cold, sterile normal saline 0.9% (i.e. challenge suspension). Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 5 minutes. Dose: 1150 cfu (doses were to be increased or lowered based on results of preceding cohorts)
Period Title: Overall Study
STARTED	10	10	10	10	16
COMPLETED	10	10	10	10	16
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Total
Arm/Group Description	Received 500 colony-forming units (CFU) of Shigella sonnei 53G. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received higher dose of Shigella sonnei 53G if ≥ 60% of subjects in Cohort 1 experienced shigellosis, or lower dose if not. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received higher dose of Shigella sonnei 53G if ≥ 60% of subjects in Cohort 2 experienced shigellosis, or lower dose if not. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received higher dose of Shigella sonnei 53G if ≥ 60% of subjects in Cohort 3 experienced shigellosis, or lower dose if not. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received higher dose of Shigella sonnei 53G if ≥ 60% of subjects in Cohort 4 experienced shigellosis, or lower dose if not. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Total of all reporting groups
Overall Participants	10	10	10	10	16	56
Age (years) [Geometric Mean (Standard Deviation) ]
Geometric Mean (Standard Deviation) [years]	35.7 (10.7)	32.3 (9.9)	34.3 (9.9)	32.2 (8.8)	30.1 (8.8)	32.6 (9.2)
Sex: Female, Male (Count of Participants)
Female	7 70%	3 30%	6 60%	7 70%	10 62.5%	33 58.9%
Male	3 30%	7 70%	4 40%	3 30%	6 37.5%	23 41.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 10%	0 0%	0 0%	0 0%	0 0%	1 1.8%
Not Hispanic or Latino	9 90%	10 100%	10 100%	10 100%	16 100%	55 98.2%
Unknown or Not Reported	0 0%	0 0%	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%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	9 90%	9 90%	10 100%	10 100%	14 87.5%	52 92.9%
White	1 10%	0 0%	0 0%	0 0%	2 12.5%	3 5.4%
More than one race	0 0%	1 10%	0 0%	0 0%	0 0%	1 1.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Shigellosis
Description	Per protocol definition: shedding of S. sonnei in the stool accompanied by moderate-severe diarrhea (4 or more loose/watery Grade 3-5 stools or 400+ gram stools per 24 hours, or requires medical intervention) and/or dysentery (a Grade 3, 4, or 5 stool with gross blood on at least 2 occasions and reportable constitutional symptoms) along with moderate fever (Oral temperature of ≥101.2°F) or one or more severe intestinal symptoms. Alternative endpoint 1 definition: severe diarrhea, or moderate diarrhea plus fever, or moderate diarrhea plus 1 moderate constitutional/enteric symptom, or dysentery. Alternative endpoint 2 definition: severe diarrhea, or moderate diarrhea plus fever, or moderate diarrhea plus 1 severe constitutional/enteric symptom, or dysentery plus 1 severe constitutional/enteric symptom
Time Frame	11 days after administration of S. sonnei

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	Received target dose of 500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 510, 717, 588, and 567 CFU). Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 817 CFU), since the attack rate of shigellosis for Cohort 1 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 913 CFU. Although the target dose was the same as Cohort 2, the safety monitoring committee felt that the per-protocol a priori definition of shigellosis was too restrictive and that increasing the dose above 1000 CFU may lead to unnecessarily high toxicity. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) since the attack rate of shigellosis for Cohort 2 and 3 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1150 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) as the final confirmatory cohort since it was felt that the disease rate and profile of Cohort 4 was appropriate. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)
Measure Participants	10	10	10	10	16
Yes	0 0%	2 20%	1 10%	4 40%	2 12.5%
No	10 100%	8 80%	9 90%	6 60%	14 87.5%
Yes	0 0%	6 60%	4 40%	7 70%	7 43.8%
No	10 100%	4 40%	6 60%	3 30%	9 56.3%
Yes	0 0%	5 50%	3 30%	6 60%	7 43.8%
No	10 100%	5 50%	7 70%	4 40%	9 56.3%

2. Secondary Outcome

Title	Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen
Description	IgA (total and S. sonnei specific) will be determined in fecal extracts using standard ELISA. IgA was recovered from stool samples using a soybean trypsin inhibitor ethylenediaminetetraacetic acid (EDTA) procedure. The shigella-antigen specific activity was calculated by dividing the endpoint titer by the IgA concentration in matched samples.
Time Frame	Baseline (days -5,-1), Day 3, Day 7, and Day 14

Outcome Measure Data

Analysis Population Description

Stool samples were not collected from all subjects at all time points. Samples containing less than 2 ug/mL of total IgA were excluded from analysis. If both baseline samples were below 2 ug/mL, the subject was excluded from analysis.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	Received target dose of 500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 510, 717, 588, and 567 CFU). Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 817 CFU), since the attack rate of shigellosis for Cohort 1 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 913 CFU. Although the target dose was the same as Cohort 2, the safety monitoring committee felt that the per-protocol a priori definition of shigellosis was too restrictive and that increasing the dose above 1000 CFU may lead to unnecessarily high toxicity. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) since the attack rate of shigellosis for Cohort 2 and 3 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1150 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) as the final confirmatory cohort since it was felt that the disease rate and profile of Cohort 4 was appropriate. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)
Measure Participants	10	10	10	10	16
Baseline 1 (Day -5)	19 (130)	11 (8)	11 (24)	17 (157)	8 (6)
Baseline 2 (Day -1)	15 (53)	8 (26)	11 (51)	9 (200)	10 (15)
Day 3	15 (65)	11 (14)	9 (11)	11 (99)	11 (21)
Day 7	49 (121)	70 (413)	80 (136)	49 (296)	42 (155)
Day 14	211 (1024)	40 (841)	226 (371)	101 (205)	57 (431)

3. Secondary Outcome

Title	Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen
Description	IgA (total and S. sonnei specific) will be determined in fecal extracts using standard ELISA. IgA was recovered from stool samples using a soybean trypsin inhibitor-EDTA procedure. The shigella-antigen specific activity was calculated by dividing the endpoint titer by the IgA concentration in matched samples.
Time Frame	Baseline (days -5,-1), Day 3, Day 7, and Day 14

Outcome Measure Data

Analysis Population Description

Stool samples were not collected from all subjects at all time points. Samples containing less than 2 ug/mL of total IgA were excluded from analysis. If both baseline samples were below 2 ug/mL, the subject was excluded from analysis.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	Received target dose of 500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 510, 717, 588, and 567 CFU). Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 817 CFU), since the attack rate of shigellosis for Cohort 1 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 913 CFU. Although the target dose was the same as Cohort 2, the safety monitoring committee felt that the per-protocol a priori definition of shigellosis was too restrictive and that increasing the dose above 1000 CFU may lead to unnecessarily high toxicity. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) since the attack rate of shigellosis for Cohort 2 and 3 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1150 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) as the final confirmatory cohort since it was felt that the disease rate and profile of Cohort 4 was appropriate. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)
Measure Participants	10	10	10	10	16
Baseline 1 (Day -5)	20 (211)	18 (60)	10 (104)	20 (638)	11 (22)
Baseline 2 (Day -1)	19 (130)	12 (111)	9 (105)	10 (403)	9 (11)
Day 3	19 (130)	15 (98)	6 (2)	16 (400)	80 (441)
Day 7	53 (140)	92 (381)	50 (124)	80 (441)	84 (498)
Day 14	422 (3317)	118 (1679)	320 (459)	403 (540)	104 (478)

4. Secondary Outcome

Title	Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen
Description	Blood (10 mL) was collected on days -1, 7, 14, 28 and 56 for Immunoglobulin A (IgA), Immunoglobulin M (IgM), and Immunoglobulin G (IgG) assay by Enzyme linked immunosorbent assay (ELISA).
Time Frame	57 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	Received target dose of 500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 510, 717, 588, and 567 CFU). Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 817 CFU), since the attack rate of shigellosis for Cohort 1 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 913 CFU. Although the target dose was the same as Cohort 2, the safety monitoring committee felt that the per-protocol a priori definition of shigellosis was too restrictive and that increasing the dose above 1000 CFU may lead to unnecessarily high toxicity. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) since the attack rate of shigellosis for Cohort 2 and 3 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1150 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) as the final confirmatory cohort since it was felt that the disease rate and profile of Cohort 4 was appropriate. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)
Measure Participants	10	10	10	10	16
Baseline (Day -1)	528 (611)	492 (547)	246 (450)	459 (420)	497 (3137)
Day 7	746 (913)	919 (3813)	400 (458)	857 (1315)	951 (6276)
Day 14	4222 (19953)	2425 (7591)	6859 (15472)	3676 (9816)	3200 (17160)
Day 28	2425 (15506)	1715 (8165)	3430 (15370)	1715 (4974)	1532 (6991)
Day 56	1393 (3897)	1131 (8350)	1372 (2418)	1300 (4188)	1131 (12550)

5. Secondary Outcome

Title	Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen
Description	Blood (10 mL) was collected on days -1, 7, 14, 28 and 56 for Immunoglobulin A (IgA), Immunoglobulin M (IgM), and Immunoglobulin G (IgG) assay by Enzyme linked immunosorbent assay (ELISA).
Time Frame	57 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	Received target dose of 500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 510, 717, 588, and 567 CFU). Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 817 CFU), since the attack rate of shigellosis for Cohort 1 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 913 CFU. Although the target dose was the same as Cohort 2, the safety monitoring committee felt that the per-protocol a priori definition of shigellosis was too restrictive and that increasing the dose above 1000 CFU may lead to unnecessarily high toxicity. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) since the attack rate of shigellosis for Cohort 2 and 3 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1150 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) as the final confirmatory cohort since it was felt that the disease rate and profile of Cohort 4 was appropriate. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)
Measure Participants	10	10	10	10	16
Baseline (Day -1)	373 (666)	264 (610)	123 (138)	348 (2073)	248 (823)
Day 7	528 (611)	1213 (10390)	264 (344)	919 (2474)	1037 (3047)
Day 14	4222 (16541)	2425 (10086)	3200 (9864)	2111 (7898)	3644 (10457)
Day 28	2425 (15598)	857 (5990)	919 (2444)	919 (4032)	1288 (4164)
Day 56	919 (877)	528 (1212)	635 (1219)	800 (2532)	591 (1784)

6. Secondary Outcome

Title	Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen
Description	Blood (10 mL) was collected on days -1, 7, 14, 28 and 56 for Immunoglobulin A (IgA), Immunoglobulin M (IgM), and Immunoglobulin G (IgG) assay by Enzyme linked immunosorbent assay (ELISA).
Time Frame	57 days

Outcome Measure Data

Analysis Population Description

No sample was available for one subject in Cohort 3 on Day 56.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	Received target dose of 500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 510, 717, 588, and 567 CFU). Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 817 CFU), since the attack rate of shigellosis for Cohort 1 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 913 CFU. Although the target dose was the same as Cohort 2, the safety monitoring committee felt that the per-protocol a priori definition of shigellosis was too restrictive and that increasing the dose above 1000 CFU may lead to unnecessarily high toxicity. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) since the attack rate of shigellosis for Cohort 2 and 3 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1150 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) as the final confirmatory cohort since it was felt that the disease rate and profile of Cohort 4 was appropriate. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)
Measure Participants	10	10	10	10	16
Baseline (Day -1)	2599 (5412)	2599 (1960)	2986 (15270)	2263 (4011)	1745 (12365)
Day 7	3430 (7619)	3940 (4221)	3200 (7303)	3940 (3477)	3490 (24798)
Day 14	10397 (31301)	7352 (30508)	14703 (14347)	11143 (18203)	8300 (28740)
Day 28	9701 (18863)	6859 (14595)	11943 (14904)	9701 (9361)	6683 (33105)
Day 56	6400 (9199)	4525 (7013)	10159 (9659)	5971 (4758)	4525 (16370)

7. Secondary Outcome

Title	Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Invaplex Antigen
Description	Blood (10 mL) was collected on days -1, 7, 14, 28 and 56 for Immunoglobulin A (IgA), Immunoglobulin M (IgM), and Immunoglobulin G (IgG) assay by Enzyme linked immunosorbent assay (ELISA).
Time Frame	57 days

Outcome Measure Data

Analysis Population Description

No sample was available for one subject in Cohort 3 on Day 56.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	Received target dose of 500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 510, 717, 588, and 567 CFU). Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 817 CFU), since the attack rate of shigellosis for Cohort 1 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 913 CFU. Although the target dose was the same as Cohort 2, the safety monitoring committee felt that the per-protocol a priori definition of shigellosis was too restrictive and that increasing the dose above 1000 CFU may lead to unnecessarily high toxicity. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) since the attack rate of shigellosis for Cohort 2 and 3 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Received target dose of 1150 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) as the final confirmatory cohort since it was felt that the disease rate and profile of Cohort 4 was appropriate. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)
Measure Participants	10	10	10	10	16
Baseline (Day -1)	348 (596)	283 (330)	115 (113)	400 (3957)	183 (1694)
Day 7	429 (451)	1056 (4076)	528 (420)	1600 (8146)	1131 (3217)
Day 14	3200 (16194)	2263 (7995)	5198 (7205)	7879 (19368)	5620 (13385)
Day 28	1970 (4825)	1213 (4011)	1715 (3660)	2425 (7953)	1822 (4613)
Day 56	985 (1046)	650 (1180)	864 (2032)	1213 (5145)	872 (2105)

Adverse Events

Time Frame	56 days
Arm/Group Title	Cohort 1		Cohort 2		Cohort 3		Cohort 4		Cohort 5
Arm/Group Description	Received target dose of 500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 510, 717, 588, and 567 CFU). Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)		Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 817 CFU), since the attack rate of shigellosis for Cohort 1 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)		Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 913 CFU. Although the target dose was the same as Cohort 2, the safety monitoring committee felt that the per-protocol a priori definition of shigellosis was too restrictive and that increasing the dose above 1000 CFU may lead to unnecessarily high toxicity. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)		Received target dose of 1500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) since the attack rate of shigellosis for Cohort 2 and 3 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)		Received target dose of 1150 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) as the final confirmatory cohort since it was felt that the disease rate and profile of Cohort 4 was appropriate. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)
All Cause Mortality
	Cohort 1		Cohort 2		Cohort 3		Cohort 4		Cohort 5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/16 (0%)
Serious Adverse Events
	Cohort 1		Cohort 2		Cohort 3		Cohort 4		Cohort 5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1		Cohort 2		Cohort 3		Cohort 4		Cohort 5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/10 (60%)		10/10 (100%)		10/10 (100%)		10/10 (100%)		15/16 (93.8%)
Cardiac disorders
Bradycardia	0/10 (0%)		0/10 (0%)		1/10 (10%)		0/10 (0%)		0/16 (0%)
Ear and labyrinth disorders
Ear infection	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		1/16 (6.3%)
Ear pain	0/10 (0%)		0/10 (0%)		0/10 (0%)		1/10 (10%)		0/16 (0%)
Gastrointestinal disorders
Abdominal Pain	1/10 (10%)		9/10 (90%)		7/10 (70%)		7/10 (70%)		9/16 (56.3%)
Anorectal discomfort	0/10 (0%)		1/10 (10%)		0/10 (0%)		1/10 (10%)		0/16 (0%)
Constipation	0/10 (0%)		0/10 (0%)		0/10 (0%)		1/10 (10%)		0/16 (0%)
Diarrhoea	2/10 (20%)		6/10 (60%)		7/10 (70%)		7/10 (70%)		12/16 (75%)
Dyspepsia	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		2/16 (12.5%)
Haematochezia	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		1/16 (6.3%)
Oropharyngeal pain	1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/16 (0%)
Vomiting	0/10 (0%)		4/10 (40%)		1/10 (10%)		1/10 (10%)		3/16 (18.8%)
Nausea	0/10 (0%)		4/10 (40%)		3/10 (30%)		3/10 (30%)		4/16 (25%)
Gas	1/10 (10%)		8/10 (80%)		5/10 (50%)		4/10 (40%)		3/16 (18.8%)
General disorders
Mucosal dryness	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		1/16 (6.3%)
Not recorded	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		1/16 (6.3%)
Malaise	0/10 (0%)		8/10 (80%)		8/10 (80%)		3/10 (30%)		1/16 (6.3%)
Fever	0/10 (0%)		3/10 (30%)		1/10 (10%)		4/10 (40%)		3/16 (18.8%)
Immune system disorders
Asthma	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		1/16 (6.3%)
Swelling face	0/10 (0%)		0/10 (0%)		0/10 (0%)		1/10 (10%)		0/16 (0%)
Urticaria	0/10 (0%)		0/10 (0%)		0/10 (0%)		1/10 (10%)		0/16 (0%)
Infections and infestations
Fungal infection	0/10 (0%)		0/10 (0%)		1/10 (10%)		0/10 (0%)		0/16 (0%)
Tooth abscess	1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/16 (0%)
Injury, poisoning and procedural complications
Anal injury	0/10 (0%)		0/10 (0%)		1/10 (10%)		0/10 (0%)		0/16 (0%)
Skin abrasion	0/10 (0%)		0/10 (0%)		1/10 (10%)		0/10 (0%)		3/16 (18.8%)
Investigations
Alanine aminotransferase increased	0/10 (0%)		1/10 (10%)		1/10 (10%)		1/10 (10%)		11/16 (68.8%)
Aspartate aminotransferase increased	0/10 (0%)		2/10 (20%)		2/10 (20%)		2/10 (20%)		1/16 (6.3%)
Blood creatinine increased	1/10 (10%)		3/10 (30%)		2/10 (20%)		1/10 (10%)		3/16 (18.8%)
Blood potassium decreased	0/10 (0%)		0/10 (0%)		0/10 (0%)		1/10 (10%)		0/16 (0%)
Blood pressure increased	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		1/16 (6.3%)
Blood pressure systolic decreased	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		6/16 (37.5%)
Blood pressure systolic increased	0/10 (0%)		4/10 (40%)		10/10 (100%)		5/10 (50%)		6/16 (37.5%)
Blood sodium increased	0/10 (0%)		0/10 (0%)		2/10 (20%)		0/10 (0%)		0/16 (0%)
Bowel movement irregularity	1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/16 (0%)
Haemoglobin decreased	2/10 (20%)		3/10 (30%)		2/10 (20%)		4/10 (40%)		4/16 (25%)
Heart rate decreased	0/10 (0%)		1/10 (10%)		0/10 (0%)		0/10 (0%)		2/16 (12.5%)
Heart rate increased	0/10 (0%)		2/10 (20%)		4/10 (40%)		7/10 (70%)		6/16 (37.5%)
Neutrophil count decreased	0/10 (0%)		1/10 (10%)		1/10 (10%)		1/10 (10%)		2/16 (12.5%)
Neutrophil count increased	0/10 (0%)		2/10 (20%)		0/10 (0%)		3/10 (30%)		0/16 (0%)
Platelet count increased	0/10 (0%)		0/10 (0%)		0/10 (0%)		1/10 (10%)		0/16 (0%)
White blood cell count decreased	0/10 (0%)		3/10 (30%)		1/10 (10%)		1/10 (10%)		3/16 (18.8%)
White blood cell count increased	0/10 (0%)		2/10 (20%)		2/10 (20%)		2/10 (20%)		0/16 (0%)
Metabolism and nutrition disorders
Anorexia	1/10 (10%)		9/10 (90%)		2/10 (20%)		4/10 (40%)		4/16 (25%)
Musculoskeletal and connective tissue disorders
Back pain	0/10 (0%)		0/10 (0%)		1/10 (10%)		0/10 (0%)		1/16 (6.3%)
Chills	1/10 (10%)		1/10 (10%)		0/10 (0%)		0/10 (0%)		0/16 (0%)
Musculoskeletal pain	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		1/16 (6.3%)
Pain in extremity	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		1/16 (6.3%)
Myalgia	1/10 (10%)		7/10 (70%)		7/10 (70%)		3/10 (30%)		5/16 (31.3%)
Arthralgia	0/10 (0%)		7/10 (70%)		1/10 (10%)		3/10 (30%)		1/16 (6.3%)
Nervous system disorders
Headache	5/10 (50%)		7/10 (70%)		8/10 (80%)		7/10 (70%)		10/16 (62.5%)
Renal and urinary disorders
Urinary tract infection	1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/16 (0%)
Reproductive system and breast disorders
Bacterial vaginosis	1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/16 (0%)
Vulvovaginal pruritus	0/10 (0%)		0/10 (0%)		0/10 (0%)		1/10 (10%)		0/16 (0%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection	1/10 (10%)		0/10 (0%)		1/10 (10%)		1/10 (10%)		2/16 (12.5%)
Skin and subcutaneous tissue disorders
Pruritus	0/10 (0%)		0/10 (0%)		0/10 (0%)		1/10 (10%)		0/16 (0%)
Skin irritation	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		1/16 (6.3%)
Vascular disorders
Haemorrhoids	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		1/16 (6.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.