Needle-free Jet Injection of Reduced-dose, Intradermal, Influenza Vaccine in >= 6 to < 24-month-old Children
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This is a sequential phase I and II, controlled, double-blinded study to determine whether
      immune responses suggesting protection against influenza can safely be induced in young
      children by two reduced doses one month apart of 0.1 mL of a trivalent inactivated influenza
      vaccine (INF) administered by the intradermal (ID) route with an investigational ID spacer on
      a United States (U.S.)-licensed needle-free jet injector (JI), compared to two standard
      intramuscular (IM) 0.25 mL doses by needle-syringe (N-S) in this age group. The locale is a
      developing country where financial restraints for the use of full-dose influenza vaccine
      would limit protection from an influenza pandemic threat, where N-Ss pose dangers and
      drawbacks in clinical use, and where Mantoux-type N-S ID injections are difficult to
      administer during mass campaigns.
    

Detailed description: 
      Randomized, observer-blinded, clinical pilot (phase I) trial of safety, followed by a
      clinical (phase II) trial of safety and non-inferiority of immune response to the standard
      route and dose for the merged subjects from both phases.

      Phase I - Influenza-vaccine naïve children (n = 48) aged >= 6 to < 24 months will be
      randomized in a 1:1:1 ratio to the following three study arms, each to receive two doses on
      days 0 and 28 of trivalent inactivated influenza (INF) vaccine (Vaxigrip®, Sanofi Pasteur,
      Lyon, France) into the left thigh (< 12 months) or left deltoid (≥ 12 months):

        -  Group "ID-JI-0.1" (n = 16) - reduced 0.1 mL INF doses administered intradermally (ID) by
           needle-free jet injector (JI) (Biojector® 2000 subcutaneous syringe no. 2 [green color
           code], with 2 cm investigational spacer, Bioject Medical Technologies, Inc., Portland,
           OR, USA)

        -  Group "IM-NS-0.1" (n = 16) - reduced 0.1 mL INF doses administered intramuscularly (IM)
           needle-syringe (NS) (via 22-25 gauge needle, minimum 25 mm/1-inch length)

        -  Group "IM-NS-0.25" (controls) (n = 16) - full 0.25 mL INF doses administered
           intramuscularly (IM) by needle-syringe (NS) (22-25 gauge needle, minimum 25 mm/1-inch
           length)

      Phase II - Upon assessment of the safety profile from phase I by the unblinded Data Safety
      Monitoring Board (DSMB), with its approval an additional 402 children will be recruited and
      randomized (134 per group) as in phase I above. Total subjects in phase I and II = 450 (150
      in each of three study arms).

      Adverse Event Diaries: Parents will be trained to complete a diary form to observe, measure,
      and record solicited local reactions for the injection site and systemic signs and symptoms
      for the child for days 0 through 7 after vaccination, plus unsolicited symptoms, illness, and
      medications for days 0 through 28.

      Followup: Return clinic visits will be scheduled on days 2, 7, and 28 after INF dose 1, at
      which times the diary card data will be recorded by staff and the card collected on day 28.
      Upon receiving dose 2 of vaccine, patients will be scheduled again to return to the study
      center 2, 7, and 28 days afterwards. The same procedures as for dose 1 regarding diary cards,
      telephone followup, and home visits will apply after dose 2.

      Upon returning to clinic on day 28 after dose 2 (day 56 after dose 1), the child will receive
      an unblinded, "insurance", full-volume, 0.25 mL dose (#3) of influenza vaccine by NS IM,
      unless he or she is in the full-dose IM control group IM-NS-0.25, in which case a mock
      injection will be administered instead of a 3rd full dose beyond the usual 2-dose series. All
      participants will return 6 months after this third injection for a fourth "bonus" dose of
      influenza vaccine to ensure protection for the following season.

      Serum Collection: Blood specimens to measure serologic responses will be collected three
      times, just prior to vaccination on day 0 (INF dose 1), on day 28 (INF dose 2), and on day 56
      (INF "insurance" dose 3).

      Ethical oversight additional to CDC IRB G by (1) World Health Organization Research Ethics
      Review Committee, (2) Consejo Nacional de Bioética en Salud, and (3) Fundación Dominicana de
      Infectología Comité de Etica/Investigaciones.
    

Intervention name(s): Vaxigrip® trivalent inactivated influenza vaccine; Intradermal spacer on Biojector® 2000 jet injector
Intervention type(s): Biological; Device
Intervention description(s): See full description elsewhere in this record.; See elsewhere in this record for full description.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: vaccination; influenza vaccine; jet injection; intradermal injection; infancy; children; dose-sparing; cutaneous vaccination; Dominican Republic; pandemic preparedness; jet injector; reduced dosage; immunogenicity; reactogenicity; safety; needle-free; immune response; hemagglutination inhibition; Infant