H5 Vaccine Alone or With Adjuvant in Healthy Adults
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This randomized, controlled, double-blinded, dose-ranging, Phase I-II study in 600 healthy
      adults, 18 to 49 years old, is designed to investigate the safety, reactogenicity, and
      dose-related immunogenicity of an investigational inactivated influenza A/H5N1 virus vaccine
      when given alone or combined with aluminum hydroxide. A secondary goal is to guide selection
      of vaccine dosage levels for expanded Phase II trials based on reactogenicity and
      immunogenicity profiles. This dose optimization will be applied to both younger and older
      subject populations in subsequent studies. Subjects who meet the entry criteria for the study
      will be enrolled at one of 4 study sites and will be randomized into one of 8 groups to
      receive 2 doses of influenza A/H5N1 vaccine containing 3.75, 7.5, 15, or 45 mcg of HA with or
      without aluminum hydroxide adjuvant by intramuscular injection. Participants may be involved
      in study related procedures for up to 8 months.
    

Detailed description: 
      This randomized, controlled, double-blinded, dose-ranging, Phase I/II study in healthy
      adults, 18 to 49 years old, is designed to investigate the safety, reactogenicity, and
      dose-related immunogenicity of an investigational inactivated influenza A/H5N1 virus vaccine
      when given alone or combined with aluminum hydroxide. The primary objectives are to:
      determine the dose-related safety of subvirion-inactivated H5N1 vaccine adjuvanted with
      aluminum hydroxide in healthy adults; determine the potential for aluminum hydroxide to
      enhance the immune response to subvirion-inactivated H5N1 vaccine in healthy adults
      approximately 1 month following receipt of 2 doses of vaccine; and provide information for
      the selection of the best dosage level for further studies. The secondary objective is to
      evaluate dose-related immunogenicity and the percent of subjects responding approximately 1
      and 7 months after the first vaccination. This dose optimization will be applied to both
      younger and older subject populations in subsequent studies. Subjects who meet the entry
      criteria for the study will be randomized into 8 groups to receive 2 doses of influenza
      A/H5N1 vaccine containing 3.75, 7.5, 15, or 45 mcg of hemagglutinin (HA) with or without
      aluminum hydroxide adjuvant by intramuscular (IM) injection (N=60 or 120/vaccine dose group).
      The first vaccination will occur on Day 0. Symptoms and signs will be assessed in the clinic
      for at least 15 minutes after inoculation, and the subjects will maintain a memory aid to
      record oral temperature and systemic and local adverse events (AEs) for 7 days after each
      immunization. Subjects will be encouraged to take their temperature around the same time each
      day. All subjects will return to the clinic 2 days and 8 days after each vaccination for
      assessment of adverse events (AEs) and concomitant medications and targeted physical
      examination (if indicated). Memory aids will be reviewed at each visit. Approximately Day 28
      after the first vaccination, subjects will return to the clinic for blood sample collection
      and safety follow-up, followed by a second vaccination. Approximately 56 days after first
      immunization (or about 28 days after the second vaccination), subjects will return to the
      clinic for immunogenicity blood sample collection, AE and concomitant medication assessment,
      and targeted physical examination (if indicated). At approximately Day 208 (7 months after
      the first vaccination), subjects will return to the clinic for a final immunogenicity blood
      sample collection and for follow-up (which includes a targeted physical examination [if
      indicated]). Blood samples collected prior to each vaccination and on Days 56 and 208 after
      the first vaccination will be tested in a central laboratory for the levels of neutralizing
      and HAI antibodies. 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 greater than or equal to 1:40 against the influenza A/H5N1 virus on Day 56. Serum
      HAI and neutralizing antibody responses (including frequencies of 4 fold or greater rise in
      titers; geometric mean titers; and proportions of subjects achieving putative protective
      titers of neutralizing antibody 1 month after each dose of vaccine and 7 months after first
      dose) also will be assessed. Although the correlate of protection for infections caused by
      influenza A/H5N1 viruses in humans is unknown, a serum neutralizing antibody titer of greater
      than or equal to 1:40 may be considered protective, based on limited data regarding the
      levels of serum neutralizing antibody present in serum samples collected from humans who
      survived infections caused by influenza A/H5N1 viruses. This study is linked to DMID protocol
      07-0022.
    

Intervention name(s): Aluminum hydroxide; Inactivated Influenza A/H5N1 Vaccine (sanofi pasteur pre-adsorbed)
Intervention type(s): Drug; Biological
Intervention description(s): Aluminum hydroxide adjuvant at 1200 mcg/mL.; Inactivated monovalent subvirion influenza H5N1 vaccine produced with and without Aluminum hydroxide adjuvant. All formulations of the H5N1 vaccine are supplied in a unit dose (0.5 mL) vial as a sterile solution for intramuscular injection. Vaccine with adjuvant is a turbid liquid whitish-grey in color. Vaccine without adjuvant is essentially clear and slightly opalescent in color.
Intervention MeSH terms: Aluminum Hydroxide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: H5N1, Influenza, vaccine