CompletedNCT03040687Updated Jun 14, 2019Results posted

Efficacy of B7A BSIgG Against E. Coli Strain B7A Challenge

A Phase 1 interventional study of Anti CS6 BSIgG product (Lot PD1601105CS) and Anti B7A BSIgG product (Lot PD1601132ET) in Healthy Volunteer, sponsored by Johns Hopkins Bloomberg School of Public Health. Completed at 1 site in United States. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-06-14.

Sponsored by Johns Hopkins Bloomberg School of Public Health · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 60
Allocation: Randomized
Ages: 18 Years to 50 Years
Sex: All

Study summary

Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea worldwide. Vaccines and therapeutics are under development to prevent ETEC disease in children and travelers. One approach is to use passive protection (antibodies) to prevent infection. The purpose of this study are to assess the safety of serum-derived bovine immunoglobulins in healthy adult subjects when orally administered and to estimate protective efficacy of those preparations against moderate-severe diarrhea upon challenge with the ETEC strain B7A.

Read the detailed description

Enterotoxigenic Escherichia coli (ETEC) is one of 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 a variety of colonization factors (CF) that help them attach to the intestinal wall. Each colonization factor has one or more surface antigens (CS). One of the major surface antigens of ETEC is CS6 (Coli surface antigen 6).

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. B7A is the only CS6 expressing ETEC challenge strain currently used.

A modality that has shown some success in the prevention of diarrhea is passive, oral administration of bovine milk IgG with specific activity against viral, bacterial and parasitic enteropathogens. Passive oral administration of Bovine Serum Immunoglobulins (BSIgG) may protect against ETEC-mediated infectious diarrhea. The hypothesized mechanism of protection stems from the passive administration of bovine anti-tip adhesion or fimbriae antibodies preventing their adherence in the human small intestine (the initial step in pathogenesis), thereby preventing downstream pathogenic processes and symptomatic illness. This study will establish the foundation for evaluating BSIgG products against numerous ETEC CFs.

This study will explore if anti-B7A and anti- CS6 BSIgG provides protection against oral challenge with B7A in healthy adult volunteers. There will be two inpatient admissions of approximately 30 subjects (up to 60 total). They will receive one of three investigational products (IP) three times daily following meals beginning 2 days prior to challenge. Each volunteer will be challenged with CS6 expressing ETEC B7A on Day 0. The investigational product/placebo will be administered for a total of 7 days, or until antibiotic treatment has been administered. The investigators hypothesize that anti-CS6 BSIgG will provide protection against B7A mediated moderate to severe diarrhea upon challenge.

Conditions studied

Healthy Volunteer

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Keywords

ETEC
Escherichia coli
enteritis
challenge
CS6
B7A

In context

Escherichia coli Infections

97 studies on the registry are indexed under Escherichia coli Infections; 17 are open to participants now.

This study's enrollment of 60 is below the median of 80 across 59 interventional studies indexed under Escherichia coli Infections.

Browse Escherichia coli Infections studies →

Lead sponsor

Johns Hopkins Bloomberg School of Public Health is the lead sponsor of 369 studies on the registry; 41 are open to participants now.

Of its 5 completed or terminated interventional studies of FDA-regulated products, 3 (60%) have results posted.

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Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 50 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Male or female between 18 and 50 years of age, inclusive.
General good health, without significant medical illness, abnormal physical examination findings or clinical laboratory abnormalities as determined by principal investigator (PI) or PI in consultation with the research monitor and sponsor.
Demonstrate comprehension of the protocol procedures and knowledge of ETEC illness by passing a written examination (pass grade ≥ 70%)
Willing to participate after informed consent obtained.
Available for all planned follow-up visits.
Negative serum pregnancy test at screening and negative serum and/or urine pregnancy test on the day of admittance to the inpatient phase for female subjects of childbearing potential. Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study. Abstinence is acceptable. Female subjects unable to bear children must have this documented (e.g., tubal ligation or hysterectomy).

Exclusion criteria

Exclusion Criteria:

General health criteria

Presence of a significant medical condition, (e.g. psychiatric conditions or gastrointestinal disease, such as peptic ulcer, symptoms or evidence of active gastritis or gastroesophageal reflux disease, inflammatory bowel disease, alcohol or illicit drug abuse/dependency, or other laboratory abnormalities which in the opinion of the investigator precludes participation in the study.
Immunosuppressive illness or Immunoglobulin A (IgA) deficiency (serum IgA \< 7 mg/dL or below the limit of detection of assay)
Evidence of confirmed infection with HIV, HBsAg, or Hepatitis C Virus (HCV), with confirmatory assays.
Use of any investigational product within 30 days preceding the receipt of the investigational products, or planned use during the active study period
Significant abnormalities in screening lab hematology or serum chemistries, as determined by PI or PI in consultation with the research monitor and sponsor.
Lactation or breastfeeding.

Research-related exclusions applicable to challenge

History of microbiologically confirmed ETEC or cholera infection in last 3 years.
Occupation involving handling of ETEC or Vibrio cholerae currently, or in the past 3 years.
Travel to countries where ETEC or cholera infection is endemic (most of the developing world) within 3 years prior to dosing.
Symptoms consistent with Travelers' Diarrhea concurrent with travel to countries where ETEC infection is endemic (most of the developing world) within 3 years prior to dosing, OR planned travel to endemic countries during the length of the study.
Vaccination for or ingestion of ETEC, cholera, or E coli heat labile toxin within 3 years prior to dosing.
Any prior experimental infection with ETEC strain B7A.

Study-specific Exclusion Criteria (potential increased risk or complicating outcome ascertainment)

Abnormal stool pattern (fewer than 3 per week or more than 3 per day).
History of diarrhea in the 2 weeks prior to planned inpatient phase.
Regular use of laxatives, antacids, or other agents to lower stomach acidity (regular defined as at least weekly).
Use of antibiotics during the 7 days before receipt of any investigational

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 60 participants (actual)

Study arms

Experimental
Anti-CS6 group
Anti-CS6 BSIgG and challenge strain CS6-expressing ETEC (B7A)
Biological: Anti CS6 BSIgG product (Lot PD1601105CS) · Biological: B7A- CS6-expressing ETEC challenge strain
Experimental
Anti-whole cell B7A
Anti- whole cell B7A (killed) BSIgG and challenge strain CS6-expressing ETEC (B7A)
Biological: Anti B7A BSIgG product (Lot PD1601132ET) · Biological: B7A- CS6-expressing ETEC challenge strain
Experimental
control Immunoglobulin group
Negative Control (Nonhyperimmune BSIgG placebo) and challenge strain CS6-expressing ETEC (B7A)
Biological: Bovine Immunoglobin Negative Control (Lot PD161071NC) · Biological: B7A- CS6-expressing ETEC challenge strain

Interventions

BiologicalAnti CS6 BSIgG product (Lot PD1601105CS)
BiologicalAnti B7A BSIgG product (Lot PD1601132ET)
BiologicalBovine Immunoglobin Negative Control (Lot PD161071NC)
BiologicalB7A- CS6-expressing ETEC challenge strain

What researchers measure

Primary outcomes

Safety of Serum Derived Bovine Immunoglobulins (BSIgG)
Number of Participants with adverse events in groups receiving B7A- and CS6- hyperimmune (BSIgG) compared with the group receiving the nonhyperimmune product.
Time frame: 28 days
Efficacy of B7A and CS6- Hyperimmune Bovine Serum Immunoglobin to Protect Against Moderate to Severe Diarrhea After Challenge With the CS6 Expressing ETEC Strain B7A
Comparison of the number and percentage of volunteers in the arms receiving the B7A- and CS6 BSIgG vs the arm receiving the nonhyperimmune BSIgG who develop moderate to severe diarrhea.
Time frame: 28 days

Results

Posted Jun 14, 2019

Participant flow

Sixty healthy adult naive subjects enrolled and received one of the three BSIgG products. Fifty-nine of those subjects were challenged with ETEC strain B7A.

Participant flow — Overall Study
Milestone	Anti-CS6 Group	Anti-whole Cell B7A	Control Immunoglobulin Group
Started	20	20	20
Completed	19	20	20
Not completed	1	0	0
Withdrew: Withdrawal by subject	1	0	0

Outcome measures

PrimarySafety of Serum Derived Bovine Immunoglobulins (BSIgG)

Number of Participants with adverse events in groups receiving B7A- and CS6- hyperimmune (BSIgG) compared with the group receiving the nonhyperimmune product.

Time frame:: 28 days
Reported as:: Count of participants · Participants

Safety of Serum Derived Bovine Immunoglobulins (BSIgG)
Participants	Anti-CS6 Group	Anti-whole Cell B7A	Control Immunoglobulin Group
Abdominal Distension	1	2	0
Abdominal Pain	2	0	1
Defecation Urgency	0	0	1
Flatulence	3	4	2
Headache	0	2	0
Nausea	0	1	0
None	14	11	16

PrimaryEfficacy of B7A and CS6- Hyperimmune Bovine Serum Immunoglobin to Protect Against Moderate to Severe Diarrhea After Challenge With the CS6 Expressing ETEC Strain B7A

Comparison of the number and percentage of volunteers in the arms receiving the B7A- and CS6 BSIgG vs the arm receiving the nonhyperimmune BSIgG who develop moderate to severe diarrhea.

Time frame:: 28 days
Reported as:: Count of participants · Participants

Efficacy of B7A and CS6- Hyperimmune Bovine Serum Immunoglobin to Protect Against Moderate to Severe Diarrhea After Challenge With the CS6 Expressing ETEC Strain B7A
Participants	Anti-CS6 Group	Anti-whole Cell B7A	Control Immunoglobulin Group
Efficacy of B7A and CS6- Hyperimmune Bovine Serum Immunoglobin to Protect Against Moderate to Severe Diarrhea After Challenge With the CS6 Expressing ETEC Strain B7A	12	7	14

Adverse events

Collected over 6 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Anti-CS6 Group	0/20 (0%)	0/20 (0%)	19/20 (95%)
Anti-whole Cell B7A	0/20 (0%)	0/20 (0%)	17/20 (85%)
Control Immunoglobulin Group	0/20 (0%)	0/20 (0%)	20/20 (100%)

Most frequent other events

Showing 10 of 11

Most frequent other events
Event	Anti-CS6 Group	Anti-whole Cell B7A	Control Immunoglobulin Group
Abdominal PainGastrointestinal disorders	12/20	7/20	12/20
Decreased appetiteGastrointestinal disorders	10/20	4/20	10/20
Abdominal DistentionGastrointestinal disorders	2/20	2/20	9/20
Defecation UrgencyGastrointestinal disorders	9/20	4/20	9/20
Abdominal tendernessGastrointestinal disorders	5/20	0/20	7/20
ChillsImmune system disorders	7/20	0/20	5/20
ArthraligiaMusculoskeletal and connective tissue disorders	2/20	0/20	5/20
Abdominal Pain lowerGastrointestinal disorders	0/20	0/20	1/20
Apthous ulcerImmune system disorders	0/20	0/20	1/20
Back painMusculoskeletal and connective tissue disorders	0/20	0/20	1/20

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Anti-CS6 Group	Anti-whole Cell B7A	Control Immunoglobulin Group	Total
Median	33.5 (25.0 to 37.5)	35.0 (31.0 to 43.0)	35.5 (26.8 to 41.8)	34 (26.8 to 42)

Sex: Female, Male
Sex: Female, Male(Participants)	Anti-CS6 Group	Anti-whole Cell B7A	Control Immunoglobulin Group	Total
Female	9	4	9	22
Male	11	16	11	38

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Anti-CS6 Group	Anti-whole Cell B7A	Control Immunoglobulin Group	Total
Hispanic or Latino	3	1	3	7
Not Hispanic or Latino	17	19	17	53
Unknown or Not Reported	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Anti-CS6 Group	Anti-whole Cell B7A	Control Immunoglobulin Group	Total
American Indian or Alaska Native	0	0	0	0
Asian	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	15	18	15	48
White	5	2	3	10
More than one race	0	0	2	2
Unknown or Not Reported	0	0	0	0

Region of Enrollment
Region of Enrollment(participants)	Anti-CS6 Group	Anti-whole Cell B7A	Control Immunoglobulin Group	Total
United States	20	20	20	60

Study locations

1 site

Johns Hopkins Center for Immunization Research
Baltimore, Maryland 21205, United States

References and documents

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. PubMed 26938983 ↗
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. PubMed 21628659 ↗
Freedman DJ, Tacket CO, Delehanty A, Maneval DR, Nataro J, Crabb JH. Milk immunoglobulin with specific activity against purified colonization factor antigens can protect against oral challenge with enterotoxigenic Escherichia coli. J Infect Dis. 1998 Mar;177(3):662-7. doi: 10.1086/514227. PubMed 9498445 ↗

Study documents

Protocol and statistical analysis plan · Nov 22, 2016

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Undecided

Timeline

Tracking since Sep 25, 2026

ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Jan 2017 to primary completion in Apr 2017, 3 months.

Results were first posted in Jun 2019, 2 years 2 months after primary completion.

Of 12 phase 1 interventional studies under Escherichia coli Infections, half reached primary completion within 14 months of starting (the median), counting those still running; a quarter within 7 and three quarters within 30. This study's 3 months is below that.

How these figures are worked out, and which studies are left out of them.

Registered: Jan 26, 2017
First posted: Feb 2, 2017
StartActual: Jan 2017
Primary completionActual: Apr 2017
CompletionActual: Aug 2017
Results first posted: Jun 14, 2019
Last update: Jun 14, 2019

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Jun 14, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03040687
Lead sponsor: Johns Hopkins Bloomberg School of Public Health
Collaborators: Naval Medical Research Center, United States Department of Defense
Responsible party: Sponsor
First posted: Feb 2, 2017
Start date: Jan 2017
Primary completion: Apr 2017
Completion: Aug 2017
Results posted: Jun 14, 2019
Last update: Jun 14, 2019

Study contacts

Kawsar R Talaat, MD

principal investigator · Johns Hopkins Center for Immunization Research

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Mar 2019. You cannot join it, but the record below documents what was studied.

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