Clinical Trial: A Phase 1, Dose Escalation Study, to Evaluate a New Shigella Sonnei Vaccine in Healthy Adults.

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 1, Randomized, Observer Blinded, Placebo Controlled, Single Center, Dose Escalation Study to Evaluate the Safety and Immunogenicity of 3 Vaccinations With Shigella

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.


Detailed Summary:
Sponsor: GSK Vaccines Institute For Global Health S.r.l.

Current Primary Outcome:

  • 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 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 ranges [ Time Frame: At Day 8 ]
    Day 8: VISIT 2 (D7 post 1st vac)
  • Number of subjects with Neutrophils results below and above the normal [ Time Frame: At Day 36 ]
    Day 36: VISIT 3.1 (D7 post 2nd vac.)
  • Number of subjects with Neutrophils results below and above the normal [ Time Frame: At Day 57 ]
    Day 57: VISIT 4 (3rd vac.)
  • Number of subjects with Neutrophils results below and above the normal [ Time Frame: At Day 64 ]
    Day 64: VISIT 4.1 (D7 post 3rd vac.)
  • Number of subjects with Neutrophils results below and above the normal [ Time Frame: At Day 85 ]

    Original Primary Outcome: To evaluate the safety profile of 5 different dosages of 1790GAHB vaccine in healthy adults. [ Time Frame: 7 and 28 days after each vaccination and entire study duration ]

    • Numbers of subjects with deviations from normal values of hematological, haematochemical blood tests and urinalysis after vaccination.
    • Numbers of subjects with solicited local and systemic reactions during 7 days following each vaccination.
    • Numbers of subjects with reported unsolicited adverse events during 28 days following each vaccination.
    • Number of subjects with reported Serious Adverse Events throughout the study duration.
    • Number of subjects with reported reactive arthritis (AE of special interest).


    Current Secondary Outcome:

    • Anti-LPS S. sonnei serum IgG Geometric mean concentration (GMCs) [ Time Frame: 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 [ Time Frame: At 28 days after each vaccination and 168 days after last vaccination ]
      Seroresponse is defined as: If half of the baseline value is greater than 25 ELISA Unit (EU) then an increase of at least 50% in the post-vaccination sample as compared to baseline [i.e. ((Post-vac minus baseline)/baseline)100% ≥ 50%]. If half of the baseline value is less or equal to 25 EU then an increase of at least 25 EU in the post-vaccination sample as compared to baseline (i.e. [post-vac minus baseline] ≥25 EU)
    • Number of subjects with high seroresponse for anti-LPS S. sonnei (IgG ELISA ≥121 EU) [ Time Frame: At baseline, at 28 days after each vaccination and at 168 days after last vaccination ]
      High seroresponse is defined as a post vaccination titer ≥X anti-LPS serum IgG units in the GSK (former Novartis) ELISA that correspond to a titer of 1:800 in the ELISA method used by Cohen et al. (1989 J. Clin. Microbiol. 27:162). To determine the value for 'X' the GSK (former Novartis) anti-LPS ELISA was calibrated against the Cohen ELISA and it was found that a concentration of 121 EU EU/mL corresponds to a titer of 1:800 in the Cohen assay


    Original Secondary Outcome: To evaluate the immunogenicity profile of 5 different dosages of 1790GAHB vaccine in healthy adults. [ Time Frame: At 28 days after 1st vaccination, 28 days after 2nd vaccination and 28 and 168 days after 3rd vaccination ]

    • IgG Geometric mean concentrations (GMCs) before (day 1), 28 days after 1st vaccination, 28 days after 2nd vaccination, 28 and 168 days after 3rd vaccination as determined by ELISA, and applicable geometric mean ratios between post vaccination and baseline samples.
    • Percentage of subjects achieving at least a four-fold rise in IgG ELISA antibody concentration 28 days after 1st vaccination, 28 days after 2nd vaccination, and 28 and 168 days after 3rd vaccination relative to the baseline concentration.
    • Stool IgA Geometric mean concentrations (GMCs as determined by ELISA, and applicable geometric mean ratios relative to the baseline concentration), may be calculated in the stool specimens of at least one cohort , provided before (day 1), 28 days after 1st vaccination, 28 days after 2nd vaccination, and 28 days after 3rd vaccination


    Information By: GSK Vaccines Institute For Global Health S.r.l.

    Dates:
    Date Received: December 17, 2013
    Date Started: February 2014
    Date Completion:
    Last Updated: June 20, 2016
    Last Verified: June 2016