Efficacy of B7A BSIgG Against E. Coli Strain B7A Challenge
Condition: Healthy Volunteer
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Anti CS6 BSIgG product (Lot PD1601105CS); Anti B7A BSIgG product (Lot PD1601132ET); Bovine Immunoglobin Negative Control (Lot PD161071NC); B7A- CS6-expressing ETEC challenge strain
Intervention type(s): Biological; Biological; Biological; Biological
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: ETEC; Escherichia coli; enteritis; challenge; CS6; B7A