Healthy Volunteer
Conditions
Keywords
ETEC, Escherichia coli, enteritis, Challenge, CS6, Enterotoxigenic
Brief summary
The purpose of this study is to determine the safe and optimal dose and regimen (fasting duration) for administering the challenge ETEC strain B7A, a CS6 expressing ETEC strain. Additionally, an assessment of homologous protection following rechallenge with B7A will be assessed.
Detailed description
Enterotoxigenic Escherichia coli (ETEC) is the most common causes of infectious diarrhea in children in resource limited countries, and is also a frequent cause of traveler's diarrhea in civilian and military travelers to endemic countries. ETEC strains express one or both of two enterotoxins (heat labile toxin (LT) and heat stable toxin (ST)) that cause help the bacteria cause the main symptom of watery diarrhea. They also express a variety of colonization factors (CF) that help them attach to the intestinal wall. Each colonization factor has one or more surface antigens (CS). Vaccines and treatments to prevent ETEC disease are under development. Some of these target specific enterotoxins or colonization factors. For over 40 years, we have used ETEC human challenge studies to understand the ETEC disease process, immune response, and more recently, to determine whether treatments or vaccines are protective or effective in mitigating disease. One concern about these challenge study is the use of high doses of bacteria given may overwhelm the protective efficacy of the vaccine or treatment. Several strains of ETEC have been used in these challenge studies; a frequently used strain is B7A (CS6+, LT+, ST+. O148:H28). This study will explore the optimal dosing strategy for B7A, in order to minimize the dose of ETEC necessary to produce disease in healthy adult volunteers. There will be two inpatient admissions. The first will examine 4 dosing and fasting regimens in healthy volunteers. The second admission will include volunteers who became ill during the first admission, as well as a new group of volunteers. This second admission will validate the optimal dose from the first admission, as well as to determine if previous infection with B7A ETEC will protect against a new infection. Trying to understand the immune response to this challenge organism may help us optimize vaccine design and delivery to protect people from this infection.
Interventions
BIOLOGICALETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer
ETEC Bacteria
Sponsors
United States Department of Defense
PATH
Naval Medical Research Center
Johns Hopkins Bloomberg School of Public Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male or female between 18 and 50 years of age, inclusive. 2. General good health, without clinically significant medical history, physical examination findings or clinical laboratory abnormalities per clinical judgment of the PI. 3. Completion of a training session and demonstration of comprehension of the protocol procedures and knowledge of ETEC-associated illness by passing a written examination. 4. Willingness to participate after informed consent obtained. 5. Availability for the study duration, including all planned follow-up visits. 6. Negative pregnancy test with understanding to not become pregnant during the study or within three months following last scheduled study visit.
Exclusion criteria
1. Presence of a significant medical condition which in the opinion of the investigator precludes participation in the study. 2. Significant abnormalities in screening hematology or serum chemistry as determined by PI or PI in consultation with the research monitor and sponsor. 3. Evidence of confirmed infection with HIV, Hepatitis B, or Hepatitis C. 4. Evidence of Immunoglobulin A (IgA) deficiency (serum IgA \< 7 mg/dL or below the limit of detection of assay). 5. Evidence of current excessive alcohol consumption or drug dependence (a targeted drug screen may be used to evaluate at the clinician's discretion). 6. Evidence of impaired immune function. 7. Recent vaccination or receipt of an investigational product (within 30 days before receipt of challenge). 8. Any other criteria which, in the investigator's opinion, would compromise the ability of the subject to participate in the study, the safety of the study, or the results of the study. 9. History of microbiologically confirmed ETEC or cholera infection in last 3 years. 10. Occupation involving handling of ETEC or Vibrio cholerae currently, or in the past 3 years. 11. Symptoms consistent with Travelers' Diarrhea concurrent with travel or planned travel to countries where ETEC infection is endemic. 12. Vaccination for or ingestion of ETEC, cholera, or E coli heat labile toxin within 3 years prior to dosing. 13. Any prior experimental infection with ETEC strain B7A. 14. Abnormal stool pattern. 15. Regular use of laxatives, antacids, or other agents to lower stomach acidity. 16. Use of any medication known to affect the immune function. 17. Known allergy to two of the following antibiotics: ciprofloxacin, trimethoprim-sulfamethoxazole, and amoxicillin.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | 6 days post-challenge | Solicited symptoms (vomiting, abdominal pain, bloating, lightheadedness, anorexia, generalized myalgia, arthralgias, abdominal cramping, constipation, nausea, malaise, headache, flatulence) |
| Moderate-severe Diarrhea | 5 days post challenge (Cohort 1 and Cohort 2 group B) 7 days post challenge (Cohort 2 Group A) | Moderate-severe diarrhea post challenge defined as * moderate diarrhea: 4 to 5 loose/liquid stools or 401-800 of loose/liquid stool in any 24-hour period * Severe diarrhea greater than or equal to 6 loose/liquid stools or greater than 800 g of loose/liquid stools in any 24-hour period |
| Moderate-severe Diarrhea in Subjects Receiving Homologous Rechallenge | 7 days post-challenge | Moderate-severe diarrhea post-challenge defined as * Moderate diarrhea: 4 to 5 loose/liquid stools or 401-800g of loose/liquid stool in any 24- hour period * Severe diarrhea: greater than or equal to 6 loose/liquid stools or greater than 800 g of loose/liquid stool in any 24-hour period |
| Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | 6 days post-challenge | Safety solicited symptoms unrelated to challenge administration (vomiting, abdominal pain, bloating, lightheadedness, anorexia, generalized myalgia, arthralgias, abdominal cramping, constipation, nausea, malaise, headache, flatulence) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immune Response to Challenge (Serology) | 28 days post challenge | — |
| Immune Response to Challenge | 6 days post challenge | Antibody in Lymphocyte Supernatant (ALS) Immunoglobin G (IgG) (CS6) coli surface antigen 6 Immunoglobin G (IgG) heat labile Toxin (LT) Immunoglobin G (IgG) (LPS) Lipopolysaccharide Immunoglobin A (IgA) (CS6) coli surface antigen 6 Immunoglobin A (IgA) heat labile Toxin (LT) Immunoglobin A (IgG) (LPS) Lipopolysaccharide |
Countries
United States
Participant flow
Pre-assignment details
Cohort 2 group A consists of 11 subjects from Cohort 1. These subjects were re admitted for a second admission. The total number of subjects enrolled was 47.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Group A 8 logs of E. coli strain B7A after overnight fast
ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria | 7 |
| Cohort 1 Group B 9 logs of E. coli strain B7A after 90 minute fast
ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria | 7 |
| Cohort 1 Group C 9 logs of E. coli strain B7A after overnight fast
ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria | 7 |
| Cohort 1 Group D 10 logs of E. coli strain B7A after 90 minute fast
ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria | 7 |
| Cohort 2 Group A subjects from Cohort 1 who met primary endpoint - 9 logs of E.coli strain B7A
ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria | 11 |
| Cohort 2 Group B Naive subjects - 9 logs of E. coli strain B7A after overnight fast
ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria | 19 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| First Admission | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 |
| First Admission | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 Group A | Cohort 1 Group B | Cohort 1 Group C | Cohort 1 Group D | Total | Cohort 2 Group A | Cohort 2 Group B |
|---|---|---|---|---|---|---|---|
| Age, Continuous Cohort 1 | 36 years | 34 years | 39 years | 35 years | 34.5 years | — | — |
| Age, Continuous Cohort 2 | — | — | — | — | 36 years | 39 years | 35 years |
| Ethnicity (NIH/OMB) Cohort 1 Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Cohort 1 Not Hispanic or Latino | 7 Participants | 6 Participants | 7 Participants | 7 Participants | 27 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Cohort 1 Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Cohort 2 Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 0 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Cohort 2 Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 25 Participants | 11 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Cohort 2 Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Cohort 1 American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Cohort 1 Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Cohort 1 Black or African American | 5 Participants | 6 Participants | 7 Participants | 6 Participants | 24 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Cohort 1 More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Cohort 1 Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Cohort 1 Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Cohort 1 White | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Cohort 2 American Indian or Alaska Native | — | — | — | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Cohort 2 Asian | — | — | — | — | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Cohort 2 Black or African American | — | — | — | — | 24 Participants | 11 Participants | 13 Participants |
| Race (NIH/OMB) Cohort 2 More than one race | — | — | — | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Cohort 2 Native Hawaiian or Other Pacific Islander | — | — | — | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Cohort 2 Unknown or Not Reported | — | — | — | — | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Cohort 2 White | — | — | — | — | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment United States Cohort 1 | 7 Participants | 7 Participants | 7 Participants | 7 Participants | 28 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States Cohort 2 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 30 Participants | 11 Participants | 19 Participants |
| Sex: Female, Male Cohort 1 Female | 2 Participants | 3 Participants | 2 Participants | 1 Participants | 8 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Cohort 1 Male | 5 Participants | 4 Participants | 5 Participants | 6 Participants | 20 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Cohort 2 Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 8 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Cohort 2 Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 22 Participants | 8 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 7 | 3 / 7 | 7 / 7 | 3 / 7 | 4 / 11 | 11 / 19 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 | 0 / 7 | 0 / 7 | 0 / 11 | 1 / 19 |
Outcome results
Primary
Moderate-severe Diarrhea
Moderate-severe diarrhea post challenge defined as * moderate diarrhea: 4 to 5 loose/liquid stools or 401-800 of loose/liquid stool in any 24-hour period * Severe diarrhea greater than or equal to 6 loose/liquid stools or greater than 800 g of loose/liquid stools in any 24-hour period
Time frame: 5 days post challenge (Cohort 1 and Cohort 2 group B) 7 days post challenge (Cohort 2 Group A)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 Group A | Moderate-severe Diarrhea | 3 Participants |
| Cohort 1 Group B | Moderate-severe Diarrhea | 3 Participants |
| Cohort 1 Group C | Moderate-severe Diarrhea | 5 Participants |
| Cohort 1 Group D | Moderate-severe Diarrhea | 5 Participants |
| Cohort 2 Group A | Moderate-severe Diarrhea | 5 Participants |
| Cohort 2 Group B | Moderate-severe Diarrhea | 11 Participants |
Primary
Moderate-severe Diarrhea in Subjects Receiving Homologous Rechallenge
Moderate-severe diarrhea post-challenge defined as * Moderate diarrhea: 4 to 5 loose/liquid stools or 401-800g of loose/liquid stool in any 24- hour period * Severe diarrhea: greater than or equal to 6 loose/liquid stools or greater than 800 g of loose/liquid stool in any 24-hour period
Time frame: 7 days post-challenge
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 Group A | Moderate-severe Diarrhea in Subjects Receiving Homologous Rechallenge | 5 Participants |
Primary
Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration
Solicited symptoms (vomiting, abdominal pain, bloating, lightheadedness, anorexia, generalized myalgia, arthralgias, abdominal cramping, constipation, nausea, malaise, headache, flatulence)
Time frame: 6 days post-challenge
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Vomiting | 0 Participants |
| Cohort 1 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Abdominal Pain | 3 Participants |
| Cohort 1 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Bloating | 5 Participants |
| Cohort 1 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Lightheadedness | 1 Participants |
| Cohort 1 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Anorexia | 4 Participants |
| Cohort 1 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Generalized Myalgia | 0 Participants |
| Cohort 1 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Arthralgias | 0 Participants |
| Cohort 1 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Abdominal Cramping | 5 Participants |
| Cohort 1 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Constipation | 1 Participants |
| Cohort 1 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Nausea | 3 Participants |
| Cohort 1 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Malaise | 4 Participants |
| Cohort 1 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Headache | 3 Participants |
| Cohort 1 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Flatulence | 7 Participants |
| Cohort 1 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Bloating | 6 Participants |
| Cohort 1 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Flatulence | 6 Participants |
| Cohort 1 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Vomiting | 0 Participants |
| Cohort 1 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Abdominal Cramping | 5 Participants |
| Cohort 1 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Malaise | 4 Participants |
| Cohort 1 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Generalized Myalgia | 1 Participants |
| Cohort 1 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Abdominal Pain | 4 Participants |
| Cohort 1 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Constipation | 1 Participants |
| Cohort 1 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Headache | 4 Participants |
| Cohort 1 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Nausea | 3 Participants |
| Cohort 1 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Anorexia | 4 Participants |
| Cohort 1 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Arthralgias | 1 Participants |
| Cohort 1 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Lightheadedness | 4 Participants |
| Cohort 1 Group C | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Arthralgias | 0 Participants |
| Cohort 1 Group C | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Constipation | 2 Participants |
| Cohort 1 Group C | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Abdominal Cramping | 5 Participants |
| Cohort 1 Group C | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Lightheadedness | 4 Participants |
| Cohort 1 Group C | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Bloating | 5 Participants |
| Cohort 1 Group C | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Vomiting | 3 Participants |
| Cohort 1 Group C | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Anorexia | 5 Participants |
| Cohort 1 Group C | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Abdominal Pain | 5 Participants |
| Cohort 1 Group C | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Malaise | 4 Participants |
| Cohort 1 Group C | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Generalized Myalgia | 0 Participants |
| Cohort 1 Group C | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Headache | 4 Participants |
| Cohort 1 Group C | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Nausea | 4 Participants |
| Cohort 1 Group C | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Flatulence | 6 Participants |
| Cohort 1 Group D | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Abdominal Cramping | 3 Participants |
| Cohort 1 Group D | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Bloating | 4 Participants |
| Cohort 1 Group D | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Lightheadedness | 1 Participants |
| Cohort 1 Group D | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Headache | 5 Participants |
| Cohort 1 Group D | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Anorexia | 4 Participants |
| Cohort 1 Group D | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Generalized Myalgia | 1 Participants |
| Cohort 1 Group D | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Arthralgias | 1 Participants |
| Cohort 1 Group D | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Constipation | 0 Participants |
| Cohort 1 Group D | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Nausea | 3 Participants |
| Cohort 1 Group D | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Flatulence | 4 Participants |
| Cohort 1 Group D | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Malaise | 3 Participants |
| Cohort 1 Group D | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Vomiting | 2 Participants |
| Cohort 1 Group D | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Abdominal Pain | 4 Participants |
| Cohort 2 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Constipation | 0 Participants |
| Cohort 2 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Generalized Myalgia | 2 Participants |
| Cohort 2 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Nausea | 3 Participants |
| Cohort 2 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Bloating | 5 Participants |
| Cohort 2 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Headache | 4 Participants |
| Cohort 2 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Abdominal Pain | 7 Participants |
| Cohort 2 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Malaise | 4 Participants |
| Cohort 2 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Anorexia | 4 Participants |
| Cohort 2 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Vomiting | 1 Participants |
| Cohort 2 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Flatulence | 7 Participants |
| Cohort 2 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Abdominal Cramping | 7 Participants |
| Cohort 2 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Arthralgias | 1 Participants |
| Cohort 2 Group A | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Lightheadedness | 2 Participants |
| Cohort 2 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Malaise | 10 Participants |
| Cohort 2 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Constipation | 0 Participants |
| Cohort 2 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Headache | 10 Participants |
| Cohort 2 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Generalized Myalgia | 3 Participants |
| Cohort 2 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Arthralgias | 3 Participants |
| Cohort 2 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Bloating | 11 Participants |
| Cohort 2 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Lightheadedness | 3 Participants |
| Cohort 2 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Nausea | 8 Participants |
| Cohort 2 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Abdominal Pain | 12 Participants |
| Cohort 2 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Abdominal Cramping | 13 Participants |
| Cohort 2 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Anorexia | 14 Participants |
| Cohort 2 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Vomiting | 3 Participants |
| Cohort 2 Group B | Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration | Flatulence | 10 Participants |
Primary
Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration
Safety solicited symptoms unrelated to challenge administration (vomiting, abdominal pain, bloating, lightheadedness, anorexia, generalized myalgia, arthralgias, abdominal cramping, constipation, nausea, malaise, headache, flatulence)
Time frame: 6 days post-challenge
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Anorexia | 1 Participants |
| Cohort 1 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Bloating | 0 Participants |
| Cohort 1 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Malaise | 1 Participants |
| Cohort 1 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Flatulence | 0 Participants |
| Cohort 1 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Vomiting | 1 Participants |
| Cohort 1 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Nausea | 1 Participants |
| Cohort 1 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Generalized myalgia | 0 Participants |
| Cohort 1 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Lightheadedness | 0 Participants |
| Cohort 1 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Headache | 1 Participants |
| Cohort 1 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Constipation | 0 Participants |
| Cohort 1 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Abdominal Cramping | 0 Participants |
| Cohort 1 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Abdominal pain | 0 Participants |
| Cohort 1 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Arthralgias | 0 Participants |
| Cohort 1 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Malaise | 0 Participants |
| Cohort 1 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Abdominal pain | 0 Participants |
| Cohort 1 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Headache | 1 Participants |
| Cohort 1 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Abdominal Cramping | 0 Participants |
| Cohort 1 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Constipation | 0 Participants |
| Cohort 1 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Nausea | 0 Participants |
| Cohort 1 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Bloating | 0 Participants |
| Cohort 1 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Flatulence | 0 Participants |
| Cohort 1 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Lightheadedness | 0 Participants |
| Cohort 1 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Anorexia | 1 Participants |
| Cohort 1 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Vomiting | 0 Participants |
| Cohort 1 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Generalized myalgia | 0 Participants |
| Cohort 1 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Arthralgias | 0 Participants |
| Cohort 1 Group C | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Anorexia | 0 Participants |
| Cohort 1 Group C | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Constipation | 0 Participants |
| Cohort 1 Group C | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Abdominal Cramping | 0 Participants |
| Cohort 1 Group C | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Malaise | 0 Participants |
| Cohort 1 Group C | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Lightheadedness | 0 Participants |
| Cohort 1 Group C | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Arthralgias | 0 Participants |
| Cohort 1 Group C | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Generalized myalgia | 0 Participants |
| Cohort 1 Group C | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Abdominal pain | 0 Participants |
| Cohort 1 Group C | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Vomiting | 0 Participants |
| Cohort 1 Group C | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Nausea | 0 Participants |
| Cohort 1 Group C | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Bloating | 0 Participants |
| Cohort 1 Group C | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Flatulence | 0 Participants |
| Cohort 1 Group C | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Headache | 1 Participants |
| Cohort 1 Group D | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Constipation | 0 Participants |
| Cohort 1 Group D | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Malaise | 0 Participants |
| Cohort 1 Group D | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Nausea | 0 Participants |
| Cohort 1 Group D | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Abdominal pain | 0 Participants |
| Cohort 1 Group D | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Bloating | 0 Participants |
| Cohort 1 Group D | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Lightheadedness | 0 Participants |
| Cohort 1 Group D | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Anorexia | 0 Participants |
| Cohort 1 Group D | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Headache | 0 Participants |
| Cohort 1 Group D | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Generalized myalgia | 0 Participants |
| Cohort 1 Group D | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Arthralgias | 0 Participants |
| Cohort 1 Group D | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Vomiting | 0 Participants |
| Cohort 1 Group D | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Abdominal Cramping | 0 Participants |
| Cohort 1 Group D | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Flatulence | 0 Participants |
| Cohort 2 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Bloating | 0 Participants |
| Cohort 2 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Vomiting | 0 Participants |
| Cohort 2 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Abdominal pain | 0 Participants |
| Cohort 2 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Lightheadedness | 0 Participants |
| Cohort 2 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Anorexia | 0 Participants |
| Cohort 2 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Generalized myalgia | 0 Participants |
| Cohort 2 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Arthralgias | 1 Participants |
| Cohort 2 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Abdominal Cramping | 0 Participants |
| Cohort 2 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Constipation | 0 Participants |
| Cohort 2 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Nausea | 0 Participants |
| Cohort 2 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Malaise | 0 Participants |
| Cohort 2 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Headache | 0 Participants |
| Cohort 2 Group A | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Flatulence | 0 Participants |
| Cohort 2 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Malaise | 0 Participants |
| Cohort 2 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Abdominal Cramping | 0 Participants |
| Cohort 2 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Arthralgias | 0 Participants |
| Cohort 2 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Generalized myalgia | 0 Participants |
| Cohort 2 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Anorexia | 0 Participants |
| Cohort 2 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Flatulence | 0 Participants |
| Cohort 2 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Headache | 0 Participants |
| Cohort 2 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Lightheadedness | 0 Participants |
| Cohort 2 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Bloating | 0 Participants |
| Cohort 2 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Abdominal pain | 0 Participants |
| Cohort 2 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Nausea | 0 Participants |
| Cohort 2 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Constipation | 0 Participants |
| Cohort 2 Group B | Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration | Vomiting | 0 Participants |
Secondary
Immune Response to Challenge
Antibody in Lymphocyte Supernatant (ALS) Immunoglobin G (IgG) (CS6) coli surface antigen 6 Immunoglobin G (IgG) heat labile Toxin (LT) Immunoglobin G (IgG) (LPS) Lipopolysaccharide Immunoglobin A (IgA) (CS6) coli surface antigen 6 Immunoglobin A (IgA) heat labile Toxin (LT) Immunoglobin A (IgG) (LPS) Lipopolysaccharide
Time frame: 6 days post challenge
Population: samples for ALS IgG and IgA were unavailable for 1 participant in cohort 2 group A Samples for ALS IgG CS6, LT and IgA CS6 were unavailable for 1 participant in cohort 2 group B
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 Group A | Immune Response to Challenge | IgG LPS | 3 participants |
| Cohort 1 Group A | Immune Response to Challenge | IgG LT | 1 participants |
| Cohort 1 Group A | Immune Response to Challenge | IgA LPS | 5 participants |
| Cohort 1 Group A | Immune Response to Challenge | IgA LT | 1 participants |
| Cohort 1 Group A | Immune Response to Challenge | IgG C66 | 2 participants |
| Cohort 1 Group A | Immune Response to Challenge | IgA CS6 | 3 participants |
| Cohort 1 Group B | Immune Response to Challenge | IgG LPS | 3 participants |
| Cohort 1 Group B | Immune Response to Challenge | IgA CS6 | 4 participants |
| Cohort 1 Group B | Immune Response to Challenge | IgG C66 | 2 participants |
| Cohort 1 Group B | Immune Response to Challenge | IgG LT | 2 participants |
| Cohort 1 Group B | Immune Response to Challenge | IgA LPS | 7 participants |
| Cohort 1 Group B | Immune Response to Challenge | IgA LT | 0 participants |
| Cohort 1 Group C | Immune Response to Challenge | IgG LT | 4 participants |
| Cohort 1 Group C | Immune Response to Challenge | IgA CS6 | 0 participants |
| Cohort 1 Group C | Immune Response to Challenge | IgG C66 | 0 participants |
| Cohort 1 Group C | Immune Response to Challenge | IgA LT | 1 participants |
| Cohort 1 Group C | Immune Response to Challenge | IgA LPS | 5 participants |
| Cohort 1 Group C | Immune Response to Challenge | IgG LPS | 1 participants |
| Cohort 1 Group D | Immune Response to Challenge | IgG LPS | 5 participants |
| Cohort 1 Group D | Immune Response to Challenge | IgG C66 | 1 participants |
| Cohort 1 Group D | Immune Response to Challenge | IgG LT | 2 participants |
| Cohort 1 Group D | Immune Response to Challenge | IgA CS6 | 2 participants |
| Cohort 1 Group D | Immune Response to Challenge | IgA LT | 1 participants |
| Cohort 1 Group D | Immune Response to Challenge | IgA LPS | 6 participants |
| Cohort 2 Group A | Immune Response to Challenge | IgA CS6 | 6 participants |
| Cohort 2 Group A | Immune Response to Challenge | IgG LT | 8 participants |
| Cohort 2 Group A | Immune Response to Challenge | IgA LPS | 8 participants |
| Cohort 2 Group A | Immune Response to Challenge | IgA LT | 4 participants |
| Cohort 2 Group A | Immune Response to Challenge | IgG C66 | 5 participants |
| Cohort 2 Group A | Immune Response to Challenge | IgG LPS | 3 participants |
| Cohort 2 Group B | Immune Response to Challenge | IgG LT | 9 participants |
| Cohort 2 Group B | Immune Response to Challenge | IgA CS6 | 6 participants |
| Cohort 2 Group B | Immune Response to Challenge | IgG C66 | 6 participants |
| Cohort 2 Group B | Immune Response to Challenge | IgA LPS | 19 participants |
| Cohort 2 Group B | Immune Response to Challenge | IgG LPS | 18 participants |
| Cohort 2 Group B | Immune Response to Challenge | IgA LT | 8 participants |
Secondary
Immune Response to Challenge (Serology)
Time frame: 28 days post challenge
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 Group A | Immune Response to Challenge (Serology) | IgA CS6 | 1 Participants |
| Cohort 1 Group A | Immune Response to Challenge (Serology) | IgG C66 | 1 Participants |
| Cohort 1 Group A | Immune Response to Challenge (Serology) | IgG LT | 2 Participants |
| Cohort 1 Group A | Immune Response to Challenge (Serology) | IgA LPS | 5 Participants |
| Cohort 1 Group A | Immune Response to Challenge (Serology) | IgG LPS | 2 Participants |
| Cohort 1 Group A | Immune Response to Challenge (Serology) | IgA LT | 1 Participants |
| Cohort 1 Group B | Immune Response to Challenge (Serology) | IgG LPS | 2 Participants |
| Cohort 1 Group B | Immune Response to Challenge (Serology) | IgA CS6 | 1 Participants |
| Cohort 1 Group B | Immune Response to Challenge (Serology) | IgG C66 | 3 Participants |
| Cohort 1 Group B | Immune Response to Challenge (Serology) | IgG LT | 1 Participants |
| Cohort 1 Group B | Immune Response to Challenge (Serology) | IgA LT | 0 Participants |
| Cohort 1 Group B | Immune Response to Challenge (Serology) | IgA LPS | 6 Participants |
| Cohort 1 Group C | Immune Response to Challenge (Serology) | IgA LPS | 4 Participants |
| Cohort 1 Group C | Immune Response to Challenge (Serology) | IgG LT | 3 Participants |
| Cohort 1 Group C | Immune Response to Challenge (Serology) | IgG LPS | 1 Participants |
| Cohort 1 Group C | Immune Response to Challenge (Serology) | IgA LT | 2 Participants |
| Cohort 1 Group C | Immune Response to Challenge (Serology) | IgA CS6 | 2 Participants |
| Cohort 1 Group C | Immune Response to Challenge (Serology) | IgG C66 | 0 Participants |
| Cohort 1 Group D | Immune Response to Challenge (Serology) | IgG LPS | 4 Participants |
| Cohort 1 Group D | Immune Response to Challenge (Serology) | IgG C66 | 0 Participants |
| Cohort 1 Group D | Immune Response to Challenge (Serology) | IgG LT | 4 Participants |
| Cohort 1 Group D | Immune Response to Challenge (Serology) | IgA CS6 | 0 Participants |
| Cohort 1 Group D | Immune Response to Challenge (Serology) | IgA LT | 1 Participants |
| Cohort 1 Group D | Immune Response to Challenge (Serology) | IgA LPS | 7 Participants |
| Cohort 2 Group A | Immune Response to Challenge (Serology) | IgG LT | 6 Participants |
| Cohort 2 Group A | Immune Response to Challenge (Serology) | IgA LPS | 6 Participants |
| Cohort 2 Group A | Immune Response to Challenge (Serology) | IgG C66 | 3 Participants |
| Cohort 2 Group A | Immune Response to Challenge (Serology) | IgA LT | 4 Participants |
| Cohort 2 Group A | Immune Response to Challenge (Serology) | IgA CS6 | 1 Participants |
| Cohort 2 Group A | Immune Response to Challenge (Serology) | IgG LPS | 4 Participants |
| Cohort 2 Group B | Immune Response to Challenge (Serology) | IgA CS6 | 2 Participants |
| Cohort 2 Group B | Immune Response to Challenge (Serology) | IgG LT | 10 Participants |
| Cohort 2 Group B | Immune Response to Challenge (Serology) | IgA LT | 3 Participants |
| Cohort 2 Group B | Immune Response to Challenge (Serology) | IgG C66 | 4 Participants |
| Cohort 2 Group B | Immune Response to Challenge (Serology) | IgA LPS | 18 Participants |
| Cohort 2 Group B | Immune Response to Challenge (Serology) | IgG LPS | 7 Participants |