Human Challenge Model Refinement With Enterotoxigenic Escherichia Coli Strain B7A

• ClinicalTrials.gov Identifier: NCT02773446
• Recruitment Status: Completed
• First Posted: May 16, 2016
• Results First Posted: July 6, 2018
• Last Update Posted: July 6, 2018
• Sponsor: Johns Hopkins Bloomberg School of Public Health
• Collaborators: United States Department of Defense; PATH; Naval Medical Research Center
• Information provided by (Responsible Party): Johns Hopkins Bloomberg School of Public Health

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Prevention
• Condition: Healthy Volunteer
• Intervention: Biological: ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer
• Enrollment: 47

Participant Flow

Recruitment Details
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.

Arm/Group Title	Cohort 1 Group A	Cohort 1 Group B	Cohort 1 Group C	Cohort 1 Group D	Cohort 2 Group A	Cohort 2 Group B
Arm/Group Description	Volunteers will receive 8 logs of E. coli strain B7A after overnight fast ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria	Volunteers will receive 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	Volunteers will receive 9 logs of E. coli strain B7A after overnight fast ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria	Volunteers will receive 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	subjects from Cohort 1 who met primary endpoint will receive optimal regimen as determined by analysis after Cohort 1. ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria	Naive subjects who will receive optimal regimen as determined by analysis after Cohort 1 ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria
Period Title: First Admission
Started	7	7	7	7	0	0
Completed	6	7	7	6	0	0
Not Completed	1	0	0	1	0	0
Reason Not Completed
Withdrawal by Subject	0	0	0	1	0	0
Lost to Follow-up	1	0	0	0	0	0
Period Title: Second Admission
Started	0	0	0	0	11	19
Completed	0	0	0	0	11	19
Not Completed	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title		Cohort 1 Group A	Cohort 1 Group B	Cohort 1 Group C	Cohort 1 Group D	Cohort 2 Group A	Cohort 2 Group B	Total
Arm/Group Description		8 logs of E. coli strain B7A after overnight fast ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria	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	9 logs of E. coli strain B7A after overnight fast ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria	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	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	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	Total of all reporting groups
Overall Number of Baseline Participants		7	7	7	7	11	19	58
Baseline Analysis Population Description		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.
Age, Continuous [1]; Median (Inter-Quartile Range); Unit of measure: Years
Cohort 1	Number Analyzed	7 participants	7 participants	7 participants	7 participants	0 participants	0 participants	28 participants
		36; (29.5 to 39)	34; (31.5 to 37)	39; (31 to 40.5)	35; (33 to 40.5)			34.5; (32 to 40)
Cohort 2	Number Analyzed	0 participants	0 participants	0 participants	0 participants	11 participants	19 participants	30 participants
						39; (32 to 41)	35; (30 to 42)	36; (30 to 41.5)
		[1] Measure Analysis Population Description: 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. Each cohort was analyzed separately.
Sex: Female, Male [1]; Measure Type: Count of Participants; Unit of measure: Participants
Cohort 1	Number Analyzed	7 participants	7 participants	7 participants	7 participants	0 participants	0 participants	28 participants
	Female	2 28.6%	3 42.9%	2 28.6%	1 14.3%	0	0	8 28.6%
	Male	5 71.4%	4 57.1%	5 71.4%	6 85.7%	0	0	20 71.4%
Cohort 2	Number Analyzed	0 participants	0 participants	0 participants	0 participants	11 participants	19 participants	30 participants
	Female	0	0	0	0	3 27.3%	5 26.3%	8 26.7%
	Male	0	0	0	0	8 72.7%	14 73.7%	22 73.3%
		[1] Measure Analysis Population Description: 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. Each cohort was analyzed separately.
Ethnicity (NIH/OMB) [1]; Measure Type: Count of Participants; Unit of measure: Participants
Cohort 1	Number Analyzed	7 participants	7 participants	7 participants	7 participants	0 participants	0 participants	28 participants
	Hispanic or Latino	0 0.0%	1 14.3%	0 0.0%	0 0.0%	0	0	1 3.6%
	Not Hispanic or Latino	7 100.0%	6 85.7%	7 100.0%	7 100.0%	0	0	27 96.4%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0	0	0 0.0%
Cohort 2	Number Analyzed	0 participants	0 participants	0 participants	0 participants	11 participants	19 participants	30 participants
	Hispanic or Latino	0	0	0	0	0 0.0%	5 26.3%	5 16.7%
	Not Hispanic or Latino	0	0	0	0	11 100.0%	14 73.7%	25 83.3%
	Unknown or Not Reported	0	0	0	0	0 0.0%	0 0.0%	0 0.0%
		[1] Measure Analysis Population Description: 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. Each cohort was analyzed separately.
Race (NIH/OMB) [1]; Measure Type: Count of Participants; Unit of measure: Participants
Cohort 1	Number Analyzed	7 participants	7 participants	7 participants	7 participants	0 participants	0 participants	28 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0	0	0 0.0%
	Asian	1 14.3%	0 0.0%	0 0.0%	0 0.0%	0	0	1 3.6%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0	0	0 0.0%
	Black or African American	5 71.4%	6 85.7%	7 100.0%	6 85.7%	0	0	24 85.7%
	White	1 14.3%	1 14.3%	0 0.0%	1 14.3%	0	0	3 10.7%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0	0	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0	0	0 0.0%
Cohort 2	Number Analyzed	0 participants	0 participants	0 participants	0 participants	11 participants	19 participants	30 participants
	American Indian or Alaska Native					0 0.0%	0 0.0%	0 0.0%
	Asian					0 0.0%	1 5.3%	1 3.3%
	Native Hawaiian or Other Pacific Islander					0 0.0%	0 0.0%	0 0.0%
	Black or African American					11 100.0%	13 68.4%	24 80.0%
	White					0 0.0%	2 10.5%	2 6.7%
	More than one race					0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported					0 0.0%	3 15.8%	3 10.0%
		[1] Measure Analysis Population Description: 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. Each cohort was analyzed separately.
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	7 participants	7 participants	7 participants	7 participants	11 participants	19 participants	58 participants
	Cohort 1	7 100.0%	7 100.0%	7 100.0%	7 100.0%	0 0.0%	0 0.0%	28 48.3%
	Cohort 2	0 0.0%	0 0.0%	0 0.0%	0 0.0%	11 100.0%	19 100.0%	30 51.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration
Description	Solicited symptoms (vomiting, abdominal pain, bloating, lightheadedness, anorexia, generalized myalgia, arthralgias, abdominal cramping, constipation, nausea, malaise, headache, flatulence)
Time Frame	6 days post-challenge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1 Group A	Cohort 1 Group B	Cohort 1 Group C	Cohort 1 Group D	Cohort 2 Group A	Cohort 2 Group B
Arm/Group Description:	8 logs of E. coli strain B7A after overnight fast ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria	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	9 logs of E. coli strain B7A after overnight fast ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria	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	subjects from Cohort 1 who met primary endpoint 9 logs of E.coli strain B7A after overnight fast ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria	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
Overall Number of Participants Analyzed	7	7	7	7	11	19
Measure Type: Count of Participants; Unit of Measure: Participants
Vomiting	0 0.0%	0 0.0%	3 42.9%	2 28.6%	1 9.1%	3 15.8%
Abdominal Pain	3 42.9%	4 57.1%	5 71.4%	4 57.1%	7 63.6%	12 63.2%
Bloating	5 71.4%	6 85.7%	5 71.4%	4 57.1%	5 45.5%	11 57.9%
Lightheadedness	1 14.3%	4 57.1%	4 57.1%	1 14.3%	2 18.2%	3 15.8%
Anorexia	4 57.1%	4 57.1%	5 71.4%	4 57.1%	4 36.4%	14 73.7%
Generalized Myalgia	0 0.0%	1 14.3%	0 0.0%	1 14.3%	2 18.2%	3 15.8%
Arthralgias	0 0.0%	1 14.3%	0 0.0%	1 14.3%	1 9.1%	3 15.8%
Abdominal Cramping	5 71.4%	5 71.4%	5 71.4%	3 42.9%	7 63.6%	13 68.4%
Constipation	1 14.3%	1 14.3%	2 28.6%	0 0.0%	0 0.0%	0 0.0%
Nausea	3 42.9%	3 42.9%	4 57.1%	3 42.9%	3 27.3%	8 42.1%
Malaise	4 57.1%	4 57.1%	4 57.1%	3 42.9%	4 36.4%	10 52.6%
Headache	3 42.9%	4 57.1%	4 57.1%	5 71.4%	4 36.4%	10 52.6%
Flatulence	7 100.0%	6 85.7%	6 85.7%	4 57.1%	7 63.6%	10 52.6%

2. Primary Outcome

Title	Moderate-severe Diarrhea
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1 Group A	Cohort 1 Group B	Cohort 1 Group C	Cohort 1 Group D	Cohort 2 Group A	Cohort 2 Group B
Arm/Group Description:	8 logs of E. coli strain B7A after overnight fast ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria	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	9 logs of E. coli strain B7A after overnight fast ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria	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	subjects from Cohort 1 who met primary endpoint- 9 logs of E. coli strain B7A after overnight fast	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
Overall Number of Participants Analyzed	7	7	7	7	11	19
Measure Type: Count of Participants; Unit of Measure: Participants
	3 42.9%	3 42.9%	5 71.4%	5 71.4%	5 45.5%	11 57.9%

3. Primary Outcome

Title	Moderate-severe Diarrhea in Subjects Receiving Homologous Rechallenge
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 2 Group A
Arm/Group Description:	subjects from Cohort 1 who met primary endpoint 9 logs of E.coli strain B7A after overnight fast ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria
Overall Number of Participants Analyzed	11
Measure Type: Count of Participants; Unit of Measure: Participants
	5 45.5%

4. Primary Outcome

Title	Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1 Group A	Cohort 1 Group B	Cohort 1 Group C	Cohort 1 Group D	Cohort 2 Group A	Cohort 2 Group B
Arm/Group Description:	8 logs of E. coli strain B7A after overnight fast ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria	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	9 logs of E. coli strain B7A after overnight fast ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria	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	subjects from Cohort 1 who met primary endpoint 9 logs of E.coli strain B7A after overnight fast ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria	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
Overall Number of Participants Analyzed	7	7	7	7	11	19
Measure Type: Count of Participants; Unit of Measure: Participants
Vomiting	1 14.3%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Abdominal pain	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Bloating	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Lightheadedness	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Anorexia	1 14.3%	1 14.3%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Generalized myalgia	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Arthralgias	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 9.1%	0 0.0%
Abdominal Cramping	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Constipation	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Nausea	1 14.3%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Malaise	1 14.3%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Headache	1 14.3%	1 14.3%	1 14.3%	0 0.0%	0 0.0%	0 0.0%
Flatulence	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

5. Secondary Outcome

Title	Immune Response to Challenge (Serology)
Description	[Not Specified]
Time Frame	28 days post challenge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1 Group A	Cohort 1 Group B	Cohort 1 Group C	Cohort 1 Group D	Cohort 2 Group A	Cohort 2 Group B
Arm/Group Description:	8 logs of E. coli strain B7A after overnight fast ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria	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	9 logs of E. coli strain B7A after overnight fast ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria	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	subjects from Cohort 1 who met primary endpoint 9 logs of E.coli strain B7A after overnight fast ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria	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
Overall Number of Participants Analyzed	7	7	7	7	11	19
Measure Type: Count of Participants; Unit of Measure: Participants
IgG C66	1 14.3%	3 42.9%	0 0.0%	0 0.0%	3 27.3%	4 21.1%
IgG LT	2 28.6%	1 14.3%	3 42.9%	4 57.1%	6 54.5%	10 52.6%
IgG LPS	2 28.6%	2 28.6%	1 14.3%	4 57.1%	4 36.4%	7 36.8%
IgA CS6	1 14.3%	1 14.3%	2 28.6%	0 0.0%	1 9.1%	2 10.5%
IgA LT	1 14.3%	0 0.0%	2 28.6%	1 14.3%	4 36.4%	3 15.8%
IgA LPS	5 71.4%	6 85.7%	4 57.1%	7 100.0%	6 54.5%	18 94.7%

6. Secondary Outcome

Title	Immune Response to Challenge
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title		Cohort 1 Group A	Cohort 1 Group B	Cohort 1 Group C	Cohort 1 Group D	Cohort 2 Group A	Cohort 2 Group B
Arm/Group Description:		8 logs of E. coli strain B7A after overnight fast ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria	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	9 logs of E. coli strain B7A after overnight fast ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria	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	subjects from Cohort 1 who met primary endpoint 9 logs of E.coli strain B7A after overnight fast ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria	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
Overall Number of Participants Analyzed		7	7	7	7	11	19
Measure Type: Number; Unit of Measure: participants
IgG C66	Number Analyzed	7 participants	7 participants	7 participants	7 participants	10 participants	18 participants
		2	2	0	1	5	6
IgG LT	Number Analyzed	7 participants	7 participants	7 participants	7 participants	10 participants	18 participants
		1	2	4	2	8	9
IgG LPS	Number Analyzed	7 participants	7 participants	7 participants	7 participants	10 participants	19 participants
		3	3	1	5	3	18
IgA CS6	Number Analyzed	7 participants	7 participants	7 participants	7 participants	10 participants	18 participants
		3	4	0	2	6	6
IgA LT	Number Analyzed	7 participants	7 participants	7 participants	7 participants	10 participants	19 participants
		1	0	1	1	4	8
IgA LPS	Number Analyzed	7 participants	7 participants	7 participants	7 participants	10 participants	19 participants
		5	7	5	6	8	19

Adverse Events

Time Frame

6 months

Adverse Event Reporting Description

[Not Specified]

Arm/Group Title

Cohort 1 Group A

Cohort 1 Group B

Cohort 1 Group C

Cohort 1 Group D

Cohort 2 Group A

Cohort 2 Group B

Arm/Group Description

8 logs of E. coli strain B7A after overnight fast ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria

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

9 logs of E. coli strain B7A after overnight fast ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria

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

subjects from Cohort 1 who met primary endpoint will receive optimal regimen as determined by analysis after Cohort 1. ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria

Naive subjects who will receive optimal regimen as determined by analysis after Cohort 1 ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer: ETEC Bacteria

All-Cause Mortality

Cohort 1 Group A

Cohort 1 Group B

Cohort 1 Group C

Cohort 1 Group D

Cohort 2 Group A

Cohort 2 Group B

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Total

--/--

--/--

--/--

--/--

--/--

--/--

Serious Adverse Events

Cohort 1 Group A

Cohort 1 Group B

Cohort 1 Group C

Cohort 1 Group D

Cohort 2 Group A

Cohort 2 Group B

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Total

0/7 (0.00%)

0/7 (0.00%)

0/7 (0.00%)

0/7 (0.00%)

0/11 (0.00%)

1/19 (5.26%)

Respiratory, thoracic and mediastinal disorders

Pulmonary Embolism † 1

0/7 (0.00%)

0

0/7 (0.00%)

0

0/7 (0.00%)

0

0/7 (0.00%)

0

0/11 (0.00%)

0

1/19 (5.26%)

19

† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (10.0)

Other (Not Including Serious) Adverse Events

Frequency Threshold for Reporting Other Adverse Events

0%

Cohort 1 Group A

Cohort 1 Group B

Cohort 1 Group C

Cohort 1 Group D

Cohort 2 Group A

Cohort 2 Group B

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Total

5/7 (71.43%)

3/7 (42.86%)

7/7 (100.00%)

3/7 (42.86%)

4/11 (36.36%)

11/19 (57.89%)

Cardiac disorders

Hypertension * 1

1/7 (14.29%)

1

1/7 (14.29%)

1

1/7 (14.29%)

1

0/7 (0.00%)

0

0/11 (0.00%)

0

0/19 (0.00%)

0

Hypotension * 1

0/7 (0.00%)

0

0/7 (0.00%)

0

0/7 (0.00%)

0

0/7 (0.00%)

0

0/11 (0.00%)

0

1/19 (5.26%)

1

Hypovolemia * 1

0/7 (0.00%)

0

0/7 (0.00%)

0

0/7 (0.00%)

0

0/7 (0.00%)

0

1/11 (9.09%)

1

0/19 (0.00%)

0

Tachycardia * 1

1/7 (14.29%)

1

1/7 (14.29%)

1

1/7 (14.29%)

1

1/7 (14.29%)

1

0/11 (0.00%)

0

2/19 (10.53%)

19

Gastrointestinal disorders

Abdominal Distention * 1

0/7 (0.00%)

0

0/7 (0.00%)

0

0/7 (0.00%)

0

1/7 (14.29%)

1

0/11 (0.00%)

0

0/19 (0.00%)

0

High pitched bowel sounds * 1

0/7 (0.00%)

0

0/7 (0.00%)

0

0/7 (0.00%)

0

1/7 (14.29%)

1

0/11 (0.00%)

0

0/19 (0.00%)

0

Hyperactive Bowel Sounds * 1

5/7 (71.43%)

5

2/7 (28.57%)

2

7/7 (100.00%)

7

3/7 (42.86%)

3

3/11 (27.27%)

3

8/19 (42.11%)

8

Rectal Pain * 1

0/7 (0.00%)

0

0/7 (0.00%)

0

0/7 (0.00%)

0

1/7 (14.29%)

1

0/11 (0.00%)

0

0/19 (0.00%)

0

Immune system disorders

Fever * 1

0/7 (0.00%)

0

0/7 (0.00%)

0

1/7 (14.29%)

1

0/7 (0.00%)

0

1/11 (9.09%)

1

3/19 (15.79%)

3

Respiratory, thoracic and mediastinal disorders

Shortness of Breath * 1

0/7 (0.00%)

0

0/7 (0.00%)

0

0/7 (0.00%)

0

1/7 (14.29%)

1

0/11 (0.00%)

0

0/19 (0.00%)

0

* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (10.0)

Limitations and 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.

Results Point of Contact

• Name/Title: Kawsar Talaat
• Organization: Johns Hopkins University
• Phone: 410-502-9627
• EMail: ktalaat@jhu.edu

Publications:

Porter CK, Riddle MS, Alcala AN, Sack DA, Harro C, Chakraborty S, Gutierrez RL, Savarino SJ, Darsley M, McKenzie R, DeNearing B, Steinsland H, Tribble DR, Bourgeois AL. An Evidenced-Based Scale of Disease Severity following Human Challenge with Enteroxigenic Escherichia coli. PLoS One. 2016 Mar 3;11(3):e0149358. doi: 10.1371/journal.pone.0149358. eCollection 2016.

Harro C, Chakraborty S, Feller A, DeNearing B, Cage A, Ram M, Lundgren A, Svennerholm AM, Bourgeois AL, Walker RI, Sack DA. Refinement of a human challenge model for evaluation of enterotoxigenic Escherichia coli vaccines. Clin Vaccine Immunol. 2011 Oct;18(10):1719-27. doi: 10.1128/CVI.05194-11. Epub 2011 Aug 18.

Chakraborty S, Harro C, DeNearing B, Ram M, Feller A, Cage A, Bauers N, Bourgeois AL, Walker R, Sack DA. Characterization of Mucosal Immune Responses to Enterotoxigenic Escherichia coli Vaccine Antigens in a Human Challenge Model: Response Profiles after Primary Infection and Homologous Rechallenge with Strain H10407. Clin Vaccine Immunol. 2015 Nov 18;23(1):55-64. doi: 10.1128/CVI.00617-15. Print 2016 Jan.

Isidean SD, Riddle MS, Savarino SJ, Porter CK. A systematic review of ETEC epidemiology focusing on colonization factor and toxin expression. Vaccine. 2011 Aug 26;29(37):6167-78. doi: 10.1016/j.vaccine.2011.06.084. Epub 2011 Jul 1. Review.

Ahmed T, Bhuiyan TR, Zaman K, Sinclair D, Qadri F. Vaccines for preventing enterotoxigenic Escherichia coli (ETEC) diarrhoea. Cochrane Database Syst Rev. 2013 Jul 5;(7):CD009029. doi: 10.1002/14651858.CD009029.pub2. Review.

McKenzie R, Porter CK, Cantrell JA, Denearing B, O'Dowd A, Grahek SL, Sincock SA, Woods C, Sebeny P, Sack DA, Tribble DR, Bourgeois AL, Savarino SJ. Volunteer challenge with enterotoxigenic Escherichia coli that express intestinal colonization factor fimbriae CS17 and CS19. J Infect Dis. 2011 Jul 1;204(1):60-4. doi: 10.1093/infdis/jir220.

Porter CK, Riddle MS, Tribble DR, Louis Bougeois A, McKenzie R, Isidean SD, Sebeny P, Savarino SJ. A systematic review of experimental infections with enterotoxigenic Escherichia coli (ETEC). Vaccine. 2011 Aug 11;29(35):5869-85. doi: 10.1016/j.vaccine.2011.05.021. Epub 2011 May 25. Review.

Lamberti LM, Bourgeois AL, Fischer Walker CL, Black RE, Sack D. Estimating diarrheal illness and deaths attributable to Shigellae and enterotoxigenic Escherichia coli among older children, adolescents, and adults in South Asia and Africa. PLoS Negl Trop Dis. 2014 Feb 13;8(2):e2705. doi: 10.1371/journal.pntd.0002705. eCollection 2014 Feb. Review.

Lanata CF, Fischer-Walker CL, Olascoaga AC, Torres CX, Aryee MJ, Black RE; Child Health Epidemiology Reference Group of the World Health Organization and UNICEF. Global causes of diarrheal disease mortality in children <5 years of age: a systematic review. PLoS One. 2013 Sep 4;8(9):e72788. doi: 10.1371/journal.pone.0072788. eCollection 2013. Review.

• Responsible Party: Johns Hopkins Bloomberg School of Public Health
• ClinicalTrials.gov Identifier: NCT02773446
• Other Study ID Numbers: CIR303 B7A
• First Submitted: May 10, 2016
• First Posted: May 16, 2016
• Results First Submitted: November 29, 2017
• Results First Posted: July 6, 2018
• Last Update Posted: July 6, 2018