A/H5N1 Vaccine in Healthy Children Aged 2-9 Years
Condition: Influenza
MeSH terms: Influenza, Human; Influenza in Birds
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purposes of this study are: to make sure that there are no serious side effects of an
      experimental inactivated influenza A/H5N1 vaccine in children; and to see how the body's
      immune system reacts to the vaccine. To look at the side effects, researchers will follow
      children closely after vaccination. To look at immune system responses, researchers will test
      the children's blood before and a number of times after vaccination. Participants will
      include up to 130 healthy children ages 2-9 years. Participants will be assigned to receive
      2, up to 3 doses of vaccine, or placebo (inactive substance). Subjects will receive at least
      2 doses of vaccine approximately 28 days apart. If data shows an enhanced immune response
      from a third vaccination, children will be offered a third dose of the vaccine. Participants
      will be involved in study related procedures for up to 13 months, including up to 6 study
      visits, plus a number of telephone calls.
    

Detailed description: 
      The goals of this study are to assess the safety, reactogenicity, and immunogenicity of
      45-microgram dosage level of monovalent subvirion influenza A/H5N1 virus vaccine administered
      by intramuscular (IM) route to healthy children. The primary goal of this study is to
      determine if this dosage level of H5N1 will result in an acceptable proportion of children
      achieving a potentially protective post vaccination antibody titer (provisionally assigned as
      a serum neutralizing titer of 1:40, based on studies conducted in Hong Kong during the 1997
      H5N1 outbreak). Approximately 130 healthy children, aged 2 through 9 years, will be enrolled
      in this multicenter, randomized, double-blinded, placebo-controlled, clinical trial to
      receive at least 2 and up to 3 doses of an inactivated influenza A/H5N1 vaccine at a
      45-microgram dose. One hundred subjects will be enrolled and randomly assigned into the
      influenza A/H5N1 vaccine dose group and 20 subjects into the placebo group (in 5:1 ratio).
      Subjects will be stratified into 2 age groups (2 to 5 years old and 6 to 9 years old).
      Vaccine or placebo will be administered into the deltoid. Subjects randomized to receive
      vaccine will receive 2 doses of the vaccine approximately 28 days apart. At approximately
      month 5, subjects' parent(s) or guardian(s) will be called to remind them of the 6-month
      follow-up visit. At the 6-month visit, subjects will be assessed for serious adverse events
      (SAEs) and the randomization assignment, ie, to vaccine or placebo, will be unmasked to the
      subject and parent(s) or guardian(s). Should data evaluating a third dose of the influenza
      A/H5N1 vaccine in adults show enhanced immunogenicity, parents or guardians of subjects who
      received vaccine will be offered a third dose, with an additional blood draw immediately
      prior to the third dose and 28 days and 6 months thereafter. The 6-month post-Dose 3 blood
      draw is optional. For subjects assigned to placebo, the parents or guardians will be offered
      the opportunity to enroll the subject into a separate open-label protocol if the 2 dose
      regimen administered to the vaccine recipients is found to be safe and immunogenic. The
      primary endpoints of the study include: adverse event (AE) and SAE information (solicited
      in-clinic and via memory aids, concomitant medications, and periodic targeted physical
      assessments, as indicated); proportion of subjects achieving a serum neutralizing antibody
      titer of 1:40 against the influenza A/H5N1 virus 28 days after receipt of second dose of
      vaccine (approximately Day 56); and geometric mean titer (GMT) and the frequency of 4-fold or
      greater increases in hemagglutination inhibition and neutralizing antibody titers 28 days
      after receipt of second dose of vaccine (approximately Day 56). The secondary endpoints of
      the study include: proportion of subjects achieving a serum neutralizing antibody titer of
      1:40 against the influenza A/H5N1 virus 1 and 6 months after receipt of first and third doses
      (if third dose will be administered [see study design]) of vaccine; GMT and the frequency of
      4-fold or greater increases in serum hemagglutination inhibition antibody titer 1 and 6
      months after receipt of first and third (if third dose will be administered [see study
      design]) doses of vaccine; and development of serum antibody responses against antigenically
      drifted variants of influenza H5N1 virus. This study is linked to protocol 06-0072.
    

Intervention name(s): Influenza A/H5N1 Vaccine; Placebo
Intervention type(s): Biological; Drug
Intervention description(s): Monovalent inactivated subvirion influenza H5N1 vaccine (derived from A/Vietnam/1203/04). Packaged in single-dose vials of 90 mcg/mL (0.7 mL/vial). Dosage 45 mcg/0.5 mL administered intramuscularly.; Normal saline administered intramuscularly.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: H5N1, Influenza, children