H5 Adult - Chiron Study of Bird Flu Vaccine
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This study is will gather critical information on the safety, tolerability, and the
      immunogenicity (capability of causing an immune response) of A/H5N1 (Bird flu) virus vaccine
      in healthy adults. Up to 400 healthy adults, aged 18 to 64, will participate. Each subject
      will participate for about 7 months and will be randomly placed in one of several different
      study groups receiving a different dose of vaccine or placebo. All subjects will receive two
      injections of their assigned study product, about 28 days apart, in the muscle. Subjects will
      keep a journal of their temperature and any adverse effects between study visits. A small
      amount of blood will also be drawn before the first injection, 7 days after each injection, 1
      month after the first injection, and 1 and 6 months after the second injection.
    

Detailed description: 
      The emergence of novel influenza A virus strains in humans (including subtype A/H5N1, H7N7
      H9N2 viruses) has added urgency to ongoing efforts to develop plans for responding to
      potential pandemic situations. This study compares the safety, reactogenicity, and
      immunogenicity of increasing doses of monovalent subvirion influenza A/H5N1 virus vaccine
      administered by intramuscular (IM) injection to healthy adults alone or combined with the
      adjuvants aluminum hydroxide or MF59. The primary objectives are to determine: the
      dose-related safety of subvirion inactivated H5N1vaccine with and without adjuvants in
      healthy adults; the dose-related immunogenicity of subvirion inactivated H5N1vaccine with and
      without adjuvants in healthy adults approximately 1 month following receipt of 2 vaccine
      doses; to provide information for the selection of the best dosage level for further studies.
      The secondary objectives are to evaluate dose-related immunogenicity and the percent of
      subjects responding about 1 and 7 months after the first vaccination. The primary endpoints
      are: adverse event (AE) or serious adverse event (SAE) information; proportion of subjects in
      each dose group achieving a serum neutralizing antibody titer of 1:40 against the influenza
      A/H5N1 virus 28 days after receipt of the second dose of vaccine; proportion of subjects in
      each dose group achieving a serum hemagglutination (HAI) antibody titer of 1:40 against the
      influenza A/H5N1 virus 28 days after receipt of the second dose of vaccine; geometric mean
      titer (GMT) and frequency of 4-fold or greater increases in neutralizing antibody titers in
      each group 28 days after receipt of the second dose of vaccine; geometric mean titer and
      frequency of 4-fold or greater increases in serum HAI antibody titers in each group 28 days
      after receipt of the second dose of vaccine. The secondary endpoints are: GMT and frequency
      of 4-fold or greater increases in neutralizing antibody titers in each group 1 month and 7
      months after receipt of the first dose of vaccine; geometric mean titer and frequency of
      4-fold or greater increases in serum HAI antibody titers in each group 1 month and 7 months
      after receipt of the first dose of vaccine; development of serum antibody responses against
      antigenically drifted variants of H5N1 influenza virus. The primary outcome measures will be
      the frequencies and severities of AEs in each group and the proportions of subjects who
      achieve a serum neutralizing antibody titer of 1:40 against the influenza A/H5N1 virus on Day
      56. About 390 healthy adults, 18 to 64 years old, inclusive, will be enrolled into this
      multicenter, randomized, placebo-controlled, dose-ranging clinical trial. Nine groups of
      randomized subjects will receive two doses of saline placebo or influenza A/H5N1 vaccine at
      45, 30, or 15 micrograms; or influenza A/H5N1 vaccine at 15 or 7.5 micrograms with MF59; or
      influenza A/H5N1 vaccine with aluminum hydroxide at 30, 15, or 7.5 micrograms (N=30, 60 or
      90/vaccine dose group total 390). Laboratory safety profile blood will be drawn prior to the
      first immunization. Subjects will receive 2 doses approximately 28 days apart. Subjects will
      be observed after inoculation and maintain a memory aid for 7 days afterwards. Subjects will
      be telephoned 1 to 3 days after vaccination for AE assessment, and they will return to the
      clinic on Day 7 for AE and concomitant medication assessment, targeted physical examination,
      safety laboratory tests and a review of the memory aid. Telephone calls assessing AEs will be
      performed after each vaccination. Serum for safety laboratory tests will be obtained prior to
      and approximately 7 days after first and second immunizations. I
    

Intervention name(s): Aluminum hydroxide; Inactivated Influenza A/H5N1 Vaccine (Chiron); MF-59; Placebo
Intervention type(s): Biological; Biological; Biological; Drug
Intervention description(s): Provided in vials that contain 0.8 mL volume per vial.; Monovalent subvirion H5N1 vaccine (HA of A/Vietnam/1203/04) provided in unit-dose vials containing 60 mcg/mL A/H5N1 HA as determined by single radial immunodiffusion. It may be formulated with MF59 or aluminum hydroxide. Dosages: 7.5 mcg, 15 mcg, 30 mcg, or 45 mcg.; Proprietary experimental adjuvant. Provided in vials that contain 0.7 mL volume per vial.; Saline placebo.
Intervention MeSH terms: Aluminum Hydroxide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: H5N1, Influenza, vaccine, parent protocol