Dose-Finding Study of Lyophilized Shigella Sonnei 53G Challenge Strain
Condition: Healthy
MeSH terms: Dysentery, Bacillary
Intervention: Shigella sonnei 53G
Intervention description: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast.
Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 56.0
Sex: All
Minimum age: 18 Years
Maximum age: 49 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: shigella

Summary:

      Development of an S. sonnei human challenge model using a newly manufactured lyophilized lot
      of S. sonnei strain 53G (Lot 1794) that can be used in the future as a challenge strain for
      all S. sonnei vaccine candidates. An adaptable dosing plan was used to determine the dose of
      Shigella sonnei 53G that induces the primary outcome in approximately 60% of subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or non-pregnant female between 18 and 49 years of age (inclusive).

          2. General good health defined as (a) no significant medical illness, (b) no clinically
             significant physical examination findings and (c) no screening laboratory values
             significantly outside the normal limits of the testing laboratory within 45 days of
             challenge.

          3. Demonstrate comprehension of the protocol procedures and knowledge of study by passing
             a written examination (pass grade ≥70%) on day -1.

          4. Willing to sign an informed consent form (ICF).

          5. Willingness to participate for an inpatient stay lasting up to 11 days and an
             outpatient follow-up lasting 6 months from challenge.

          6. Willing to not smoke during the inpatient stay.

          7. Available for all planned follow-up visits.

          8. Negative serum pregnancy test at screening and negative urine pregnancy test on the
             day of admission to the inpatient phase for female subjects of childbearing potential.
             Females of childbearing potential must agree to use an effective method of birth
             control (birth control pills, injection hormonal contraceptive, implant hormonal
             contraceptive,

             hormonal patch, intrauterine device (IUD), sterilization by hysterectomy or tubal
             ligation, spermicidal products and barrier methods such as cervical sponge, diaphragm,
             or condom) within two months of challenge and during the entire study. Abstinence is
             acceptable. A woman is eligible if she is monogamous with a vasectomized partner.

          9. Willing to not donate blood for up to 6 months after completion of the inpatient phase
             of the study.

         10. Willing to refrain from participation in another investigational vaccine or drug trial
             at least until after completion of the 6 month follow-up safety call.

        Exclusion Criteria:

          1. Presence of a significant medical condition (e.g. psychiatric conditions, alcohol or
             illicit drug abuse/dependency, or gastrointestinal disease, such as peptic ulcer,
             symptoms or evidence of active gastritis or gastroesophageal reflux disease,
             inflammatory bowel disease), or other laboratory abnormalities which in the opinion of
             the investigator precludes participation in the study.

          2. Immunosuppressive illness or immunoglobulin A (IgA) deficiency

          3. Positive serology results for HIV, HBsAg, hepatitis C virus (HCV), or syphilis (RPR)
             antibodies.

          4. Evidence of inflammatory arthritis on exam and/or human leukocyte antigen B27
             (HLA-B27) positive.

          5. Family history of inflammatory arthritis.

          6. Significant abnormalities in screening lab hematology or serum chemistry, as
             determined by PI.

          7. Allergy to fluoroquinolones or trimethoprim-sulfamethoxazole

          8. Fewer than 3 stools per week or more than 3 stools per day as the usual frequency.

          9. History of diarrhea in the 2 weeks prior to planned inpatient phase

         10. Use of antibiotics during the 7 days before receiving the challenge inoculum dosing

         11. Use of prescription and/or over the counter (OTC) medications that contain Imodium,
             acetaminophen, aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs,
             during the 48 hours prior to investigational product administration

         12. Travel within two years prior to dosing to countries where Shigella infection is
             endemic.

         13. Use of any medication known to affect the immune function [e.g., oral steroids,
             parenteral steroids, or high-dose inhaled steroids (>800 μg/day of beclomethasone
             dipropionate or equivalent and others): nasal and topical steroids are allowed] within
             30 days preceding receipt of the challenge inoculum or planned use during the active
             study period.

         14. Serologic evidence of Shigella sonnei (titer > 1:2500)

         15. A positive urine test for opiates.

         16. A chronic disease (such as hypertension, hyperlipidemia or anxiety/depression) for
             which doses of prescription medications are not stable for at least the past 3 months.

         17. Scheduled and/or long-term use of oral steroids, parenteral steroids, or high-dose
             inhaled steroids (>800 μg/day of beclomethasone dipropionate or equivalent) within the
             preceding 6 months (Nasal, intra-articular, and topical steroids are allowed)

         18. Have immunocompromised household contacts.

         19. A clinically significant abnormality on physical examination, including a systolic
             blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg, or a resting pulse
             >100 beats/min or <55 beats/min (<50 beats/min for conditioned athletes).

         20. Pregnant, nursing, or plan to become pregnant within 6 months of receipt of the study
             product.

         21. In the 4 weeks following challenge, subject will be living with or having daily
             contact with elderly persons aged 70 years or more, diapered individuals, persons with
             disabilities, children <2 years old, or a woman known to be pregnant or nursing, or
             anyone with diminished immunity. This includes contact at home, school, day-care,
             nursing homes, or similar places.

         22. Work in a health care setting, day care center, or as a food handler in the 4 weeks
             following the challenge with S. sonnei.

         23. Use of any investigational drug or any investigational vaccine within 60 days
             preceding challenge, or planned use during the 6 months after receipt of the study
             agent.

         24. Have received a licensed, live vaccine within 28 days or a licensed inactivated
             vaccine within 14 days of receiving the challenge inoculum.

         25. Inability to comply with inpatient rules and regulations.

         26. Has any other condition that, in the opinion of the Investigator, would jeopardize the
             safety or rights of a participant or would render the subject unable to comply with
             the protocol.

         27. Received blood or blood products within the past six months.