Clinical Trial: Evaluate a New Shigella Sonnei Vaccine Administered Either by Intradermal, Intranasal or Intramuscular Route in Healthy Adults

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

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

Brief Summary:

This Phase 1 clinical trial is aimed to evaluate the safety and immunogenicity of 3 doses of a candidate vaccine against Shigella sonnei (1790GAHB vaccine) when administered at different dosages by different routes (intradermally, intranasally or intramuscularly) 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 52 eligible subjects will be assigned to one of three sequential cohorts as follows:

Cohort A) 0.1 μg ID and 5 μg IN Cohort B) 1 μg ID and 20 μg IN Cohort C) 10 μg ID, 80 μg IN and 5 μg IM 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. Specifically for IN and ID administration routes, 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/swelling refers to: ≥25 mm in diameter. Grade 3 (severe) refers to erythema/induration/swelling >100 mm in diameter.

    Grade 3 (severe) for injection site pain/nasal pain/facial edema/rhinorrhea 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.)

  • Original Primary Outcome:

    • To evaluate the safety profile of different dosages of NVGH 1790GAHB vaccine in adults, when administered intradermally, intranasally or intramuscularly [ Time Frame: Day 28 after each vaccination ]
      • Numbers of subjects with deviations from normal values of hematology, renal, bone and liver panels and urinalysis (after 2nd and 3rd vaccination).
      • Numbers of subjects with reported unsolicited adverse events during 28 days following each vaccination.
    • To evaluate the safety profile of different dosages of NVGH 1790GAHB vaccine in adults, when administered intradermally, intranasally or intramuscularly [ Time Frame: Day 7 after each vaccination ]
      • Numbers of subjects with deviations from normal values of hematology, renal, bone and liver panels and urinalysis (after 1st vaccination)
      • Numbers of subjects with reported solicited adverse events during 7 days following each vaccination.
    • To evaluate the safety profile of different dosages of NVGH 1790GAHB vaccine in adults, when administered intradermally, intranasally or intramuscularly [ Time Frame: Throughout the study duration e.g. approximately 9 months ]
      • Adverse Events leading to study withdrawal
      • All Serious Adverse Events
      • All Adverse Events of special Interest (reactive arthritis according the s

        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 different dosages of NVGH 1790GAHB vaccine in adults when administered intradermally, intranasally, or intramuscularly [ Time Frame: Day 56 ]
          • IgG Geometric mean concentrations (GMCs) 28 days after 2nd 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 2nd vaccination relative to the baseline concentration.
          • Stool IgA GMCs 28 days after 2nd vaccination as determined by ELISA, and applicable geometric mean ratios relative to baseline concentration.
          • Number of subjects achieving at least a four-fold rise in IgA ELISA antibody concentration 28 days after 2nd vaccination relative to the baseline concentration.
        • To evaluate the immunogenicity profile of different dosages of NVGH 1790GAHB vaccine in adults when administered intradermally, intranasally, or intramuscularly [ Time Frame: Day 28 ]
          • IgG Geometric mean concentrations (GMCs) before (day 1) and 28 days after 1st 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 relative to the baseline concentration.
          • Stool IgA GMCs before (day 1), 28 days after 1st vaccination as determined by ELISA, and applicable geometric mean ratios relative to baseline concentration.
          • Number of subjects achieving at least a four-fold rise in IgA ELISA antibody concentration 28 days after 1st vaccination relative to the baseline concentration.
        • To evaluate the immunogenicity profile of different dosages of NVGH 1790GAHB vaccine in adults when administered intradermally, intranasally, or intramuscularly [ Time Frame: Day 84 ]
          • IgG Geometric mean concentrations (GMCs) 28 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 3rd vaccination relative to the baseline concentration.
          • Stool IgA GMCs 28 days after 3rd vaccination as determined by ELISA, and applicable geometric mean ratios relative to baseline concentration.
          • Number of subjects achieving at least a four-fold rise in IgA ELISA antibody concentration 28 days after 3rd vaccination relative to the baseline concentration.
        • To evaluate the immunogenicity profile of different dosages of NVGH 1790GAHB vaccine in adults when administered intradermally, intranasally, or intramuscularly [ Time Frame: Day 252 ]
          • IgG Geometric mean concentrations (GMCs) 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 168 days after 3rd vaccination relative to the baseline concentration.
          • Stool IgA GMCs 168 days after 3rd vaccination as determined by ELISA, and applicable geometric mean ratios relative to baseline concentration.
          • Number of subjects achieving at least a four-fold rise in IgA ELISA antibody concentration 168 days after 3rd vaccination relative to the baseline concentration.


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

        Dates:
        Date Received: January 2, 2014
        Date Started: March 2014
        Date Completion:
        Last Updated: June 20, 2016
        Last Verified: June 2016