A Phase 1, Randomized, Observer Blinded, Placebo Controlled, Single Center, Dose Escalation Study to Evaluate the Safety and Immunogenicity of 3 Vaccinations With Shigella Sonnei Vaccine (1790GAHB) Administered Intramuscularly in Healthy Adults.
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Shigellosis
- Sponsor
- GSK Vaccines Institute For Global Health S.r.l.
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Number of Subjects With Solicited Systemic Reaction After Any Vaccination
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Males and females of age ≥18 years to ≤45 years.
- •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.
- •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.
- •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.
- •Individuals affiliated to a social security regimen.
Exclusion Criteria
- •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.
- •Individuals with any progressive or severe neurological disorder, seizure disorder or Guillain-Barré syndrome.
- •Individuals who are not able to understand and to follow all required study procedures for the whole period of the study.
- •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.
- •Individuals human leukocyte antigen (HLA) -B27 positive and/or with history of reactive arthritis.
- •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.
- •Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
- •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).
- •Individuals who have any malignancy or lymphoproliferative disorder.
- •Individuals with history of allergy to vaccine components.
Outcomes
Primary Outcomes
Number of Subjects With Solicited Systemic Reaction After Any Vaccination
Time Frame: During a 7-day (Days 1 to 7) post vaccination period following any injection
Any= Incidence of any symptom regardless of intensity grade. Grade 3 = symptom that prevented daily activities
Number of Subjects With Neutrophils Results Below and Above the Normal
Time Frame: At Day 225
Day 225: VISIT 6 (6 months post 3rd vac.)
Number of Subjects With Solicited Local Reaction After Any Vaccination
Time Frame: During a 7-day (Days 1-7) post vaccination period following any injection
Any erythema/induration refers to: ≥25 mm in diameter. Grade 3 (severe) refers to erythema/induration \>100 mm in diameter. Grade 3 (severe) for injection site pain refers to: prevents daily activity
Number of Subjects With Neutrophils Results Below and Above the Normal Ranges
Time Frame: At Day 8
Day 8: VISIT 2 (D7 post 1st vac)
Secondary Outcomes
- Number of Subjects With High Seroresponse for Anti-LPS S. Sonnei (IgG ELISA ≥121 EU)(At baseline, at 28 days after each vaccination and at 168 days after last vaccination)
- Anti-LPS S. Sonnei Serum IgG Geometric Mean Concentration (GMCs)(At baseline, at 28 days after each vaccination and at 168 days after last vaccination)
- Number of Subjects With Seroresponse for Anti-LPS S. Sonnei(At 28 days after each vaccination and 168 days after last vaccination)