A Phase 1, Dose Escalation Study, to Evaluate a New Shigella Sonnei Vaccine in Healthy Adults.
Condition: Shigellosis
MeSH terms: Dysentery, Bacillary
Intervention: S. sonnei 1790GAHB; Placebo
Intervention MeSH terms: Vaccines
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: prevention; Shigella sonnei

Summary:

      This Phase 1 clinical trial is aimed to evaluate the safety and immunogenicity of 3 doses of
      5 sequentially escalating dosages of a candidate vaccine against Shigella sonnei (1790GAHB
      vaccine) administered by intramuscular route in healthy adults (18 to 45 years of age at
      enrollment). The safety profile of the 1790GAHB vaccine is evaluated in comparison to that of
      placebo (GAHB-Placebo), constituted by an aluminum hydroxide suspension having the same
      concentration as study vaccine formulations. A total of 50 eligible subjects will be assigned
      to one of five sequential cohorts of 10 subjects each.

      Within each cohort, in an observer-blind fashion, subjects will be randomized to receive
      three vaccinations, four weeks apart, of either 1790GAHB vaccine (at five antigen
      concentrations) or GAHB placebo. A Data Safety Monitoring Board will be in place to receive a
      summary of all safety data obtained during one week follow-up post-first vaccination with the
      lower dose. Based on evaluation of the safety data, the Data Safety Monitoring Board will
      make a recommendation, as to whether the next cohort should be vaccinated with higher antigen
      concentration or not.

      Expected duration of the study for an individual subject is 9 months. Each subject will be
      followed-up for 6 months after the 3rd vaccination.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Males and females of age ≥18 years to ≤45 years.

          2. Individuals who, after the nature of the study has been explained to them, and prior
             to any protocol specific procedures being performed, have given written consent
             according to local regulatory requirements.

          3. Individuals in good health as determined by the outcome of medical history, physical
             examination, hematological / hematochemical blood tests (including presence of high
             antibody titers against S. sonnei by agglutination test), urinalysis and clinical
             judgment of the investigator.

          4. If women of child-bearing potential, have a negative pregnancy test prior study
             vaccination and willingness to use acceptable birth control measures for the entire
             study duration.

          5. Individuals affiliated to a social security regimen.

        Exclusion Criteria:

          1. Individuals with behavioral or cognitive impairment or psychiatric disease that, in
             the opinion of the investigator, may interfere with the subject's ability to
             participate in the study.

          2. Individuals with any progressive or severe neurological disorder, seizure disorder or
             Guillain-Barré syndrome.

          3. Individuals who are not able to understand and to follow all required study procedures
             for the whole period of the study.

          4. Individuals with history of any illness that, in the opinion of the investigator,
             might interfere with the results of the study or pose additional risk to the subjects
             due to participation in the study.

          5. Individuals human leukocyte antigen (HLA) -B27 positive and/or with history of
             reactive arthritis.

          6. Individuals with known or suspected HIV infection or HIV related disease, with history
             of an autoimmune disorder or any other known or suspected impairment /alteration of
             the immune system, or under immunosuppressive therapy including use of systemic
             corticosteroids or chronic use of inhaled high-potency corticosteroids (i.e.
             prednisone, or equivalent ≥10 mg/day) within the previous 28 days, or in chemotherapy
             treatment within the past 168 days.

          7. Individuals with a known bleeding diathesis, or any condition that may be associated
             with a prolonged bleeding time.

          8. Individuals with any serious chronic or progressive disease according to judgment of
             the investigator (e.g., neoplasm, insulin dependent diabetes, cardiac, renal or
             hepatic disease).

          9. Individuals who have any malignancy or lymphoproliferative disorder.

         10. Individuals with history of allergy to vaccine components.

         11. Individuals participating in any clinical trial with another investigational product
             28 days prior to first study visit or intent to participate in another clinical study
             at any time during the conduct of this study.

         12. Individuals who received any other vaccines within 4 weeks prior to enrollment in this
             study or who are planning to receive any vaccine within the entire study duration
             except influenza vaccination, which is not allowed within the period included between
             28 days before 1st vaccination and 28 days after 3rd vaccination.

         13. Individuals who have received blood, blood products, and/or plasma derivatives
             including parenteral immunoglobulin preparations in the past 12 weeks.

         14. Individuals who are part of study personnel or close family members to the personnel
             conducting this study or employees of the clinical trial site institution.

         15. Individuals with body temperature > 38.0 degrees Celsius within 3 days of intended
             study vaccination.

         16. Individuals with Body Mass Index (BMI)> 30 kg/m2

         17. Individuals with history of substance or alcohol abuse within the past 2 years.

         18. Women who are pregnant or are breast-feeding, or are of childbearing age who have not
             used or do not plan to use acceptable birth control measures, for the duration of the
             study.

         19. Females with history of stillbirth, neonatal loss, or previous infant with anomaly.

         20. Individuals who have a previously laboratory confirmed or suspected disease caused by
             S. sonnei.

         21. Individuals who have had household contact with/and or intimate exposure to an
             individual with laboratory confirmed S. sonnei.

         22. Any condition, which, in the opinion of the investigator may pose an increased and
             unreasonable safety risk to the subject if participating to the present study