NCT03040687

Efficacy of B7A BSIgG Against E. Coli Strain B7A Challenge

Protective Efficacy of Orally Delivered Bovine Serum Immunoglobulin (BSIgG) Specific for the Colonization Factor CS6 Following Challenge With the CS6-expressing Enterotoxigenic E. Coli (ETEC) Strain B7A

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (actual)
• Sponsor: Johns Hopkins Bloomberg School of Public Health · Academic / Other
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

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.

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

• Healthy Volunteer

Interventions

Type	Name	Description
BIOLOGICAL	Anti CS6 BSIgG product (Lot PD1601105CS)
BIOLOGICAL	Anti B7A BSIgG product (Lot PD1601132ET)
BIOLOGICAL	Bovine Immunoglobin Negative Control (Lot PD161071NC)
BIOLOGICAL	B7A- CS6-expressing ETEC challenge strain

Timeline

• Start date: 2017-01-01
• Primary completion: 2017-04-01
• Completion: 2017-08-01
• First posted: 2017-02-02
• Last updated: 2019-06-14
• Results posted: 2019-06-14

Locations

1 site across 1 country: United States