Dose Escalating Study of a Prototype CS6 Subunit Vaccine With a Modified Heat-labile Enterotoxin From Enterotoxigenic Escherichia Coli (ETEC)
Condition: Diarrhea
MeSH terms: Escherichia coli Infections; Diarrhea
Intervention: CssBA; dmLT
Intervention description: Recombinant enterotoxigenic Escherichia coli (ETEC) surface antigen 6 containing modified structural subunits A and B; Escherichia coli double mutant heat-labile toxin with mutations at amino acids 192 and 211
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: ETEC; Escherichia coli; enteric

Summary:

      This study will evaluate the safety of a prototype Coli surface antigen 6 (CS6) subunit
      vaccine (CssBA) alone or in combination with Escherichia coli double mutant heat labile toxin
      (dmLT) given by intramuscular (IM) injection.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Healthy, adult, male or female, age 18 to 45 years (inclusive) at the time of
             enrollment.

          2. Completion and review of comprehension test (achieved > 70% accuracy).

          3. Signed informed consent document.

          4. Available for the required follow-up period and scheduled clinic visits.

          5. Women: Negative pregnancy test with understanding (through informed consent process)
             to not become pregnant during the study or within three (3) months following last
             vaccination.

        Exclusion Criteria:

          1. Health problems (for example, intercurrent febrile illness, chronic medical conditions
             such as psychiatric conditions, diabetes mellitus, hypertension or any other condition
             that might place the subject at increased risk of adverse events) - study clinicians,
             in consultation with the PI, will use clinical judgment on a case-by-case basis to
             assess safety risks under this criterion. The PI will consult with the Research
             Monitor as appropriate.

          2. Clinically significant abnormalities on physical examination.

          3. Immunosuppressive drugs (use of systemic corticosteroids or chemotherapeutics that may
             influence antibody development) or illness (including immunoglobulin A [IgA]
             deficiency, defined by serum IgA < 7 mg/dL).

          4. Women who are pregnant or planning to become pregnant during the study period plus
             three (3) months beyond the last received dose and currently nursing women.

          5. Participation in research involving another investigational product (defined as
             receipt of investigational product or exposure to invasive investigational device) 30
             days before planned date of first vaccination or anytime through the last study safety
             visit.

          6. Positive blood test for Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV),
             human immunodeficiency virus (HIV)-1/2.

          7. Clinically significant abnormalities on basic laboratory screening.

          8. Exclusionary skin disease history/findings that would confound assessment or prevent
             appropriate local monitoring of adverse events (AEs), or possibly increase the risk of
             a local AE

          9. History of chronic skin disease (clinician judgement)

         10. Acute skin infection/eruptions on the upper arms including fungal infections, severe
             acne or active contact dermatitis

         11. Allergies that may increase the risk of AEs

         12. Regular use (weekly or more often) of antidiarrheal, anti-constipation, or antacid
             therapy

         13. Abnormal stool pattern (fewer than 3 stools per week or more than 3 stools per day) on
             a regular basis; loose or liquid stools on other than an occasional basis

         14. History of microbiologically confirmed ETEC or cholera infection in the last 3 years

         15. Travel to countries where ETEC or V. cholerae or other enteric infections are endemic
             (most of the developing world) within 3 years prior to dosing (clinician judgement)

         16. Symptoms consistent with Travelers' Diarrhea or 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

         17. Vaccination for or ingestion of ETEC, cholera, or E. coli heat labile toxin within 3
             years prior to dosing

         18. Occupation involving handling of ETEC or V. cholerae currently, or in the past 3 years