Dose Escalating Study of Intramuscular Invaplex[AR-DETOX]
Condition: Diarrhea
MeSH terms: Diarrhea
Intervention: Invaplex[AR-DETOX]; Placebo
Intervention description: Detoxified Shigella flexneri 2a Artificial Invasin Complex (Invaplex[AR-Detox]) Vaccine; Saline
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 58.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Shigella flexneri 2a; Enteric; Shigella

Summary:

      The main purpose of this study is to evaluate the safety of a Shigella flexneri 2a detoxified
      artificial invasin complex (Invaplex[AR-Detox]) vaccine candidate administered by
      intramuscular immunization.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy, adult, male or female, age 18 to 50 years (inclusive) at the time of
             enrollment.

          -  Completion and review of comprehension test (achieved ≥ 70% accuracy, two attempts
             allowed).

          -  Provide written informed consent before initiation of any study procedures.

          -  Agrees to complete all study visits and procedures and to provide a screening stool
             sample.

          -  Women of childbearing capacity: Negative pregnancy test with understanding (through
             informed consent process) to not become pregnant during the study or within three (3)
             months following the last vaccine dose.

        Exclusion Criteria:

          -  Health problems (for example, chronic medical conditions such as psychiatric
             conditions, diabetes mellitus, hypertension, or any other conditions that might place
             the subjects at increased risk of adverse events) - study clinicians, in consultation
             with the Principal Investigator (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.

          -  History of autoimmune disorders, cardiovascular and renal disease.

          -  Use of immunosuppressive medications (systemic corticosteroids or chemotherapeutics
             that may influence antibody development), or immunosuppressive illness, including
             immunoglobulin A (IgA) deficiency (defined by serum IgA < 7 mg/dL).

          -  Women who are pregnant or planning to become pregnant during the study period plus 3
             months beyond the last vaccine dose and currently nursing women.

          -  Participation in research involving another investigational product (defined as
             receipt of an investigational product or exposure to an invasive investigational
             device) 30 days before planned date of first vaccination or anytime throughout the
             duration of the study until the last in-clinic study safety visit.

          -  Positive blood test for hepatitis B surface antigen (HBsAG), hepatitis C virus
             antibody (HCV Ab), human immunodeficiency virus (HIV)-1/HIV-2 antibody.

          -  Clinically significant abnormalities on basic laboratory screening tests.

          -  Systemic antimicrobial treatment (i.e., topical treatments are not an exclusion)
             within 1 week before administration of the first vaccine dose.

          -  Allergies that may increase the risk of adverse events (AEs).

          -  Regular use (weekly or more often) of antidiarrheal, anti-constipation, or antacid
             therapy.

          -  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.

          -  Personal or family history of an inflammatory arthritis.

          -  Positive blood test for human leukocyte antigen (HLA) B27 (associated with increased
             risk of reactive arthritis secondary to Shigella infection)

          -  History of allergy to any vaccine.

          -  Exclusionary skin disease history/findings that would confound assessment or prevent
             appropriate local monitoring of AEs, or possibly increase the risk of a local AE.

          -  Serum immunoglobulin G (IgG) titer > 2500 to Shigella flexneri 2a lipopolysaccharide
             antigen (LPS).

          -  History of microbiologically confirmed Shigella infection.

          -  Received previous licensed or experimental Shigella vaccine or live Shigella
             challenge.

          -  Travel to countries where Shigella or other enteric infections are endemic (most of
             the developing world) within two years prior to dosing (clinician judgement).

          -  Occupation involving handling of Shigella bacteria currently, or in the past 3 years.