Dose-Escalating Trial Using Vero Cell-culture Derived H5N1 +/- Aluminum in Adults
Condition: Influenza
MeSH terms: Influenza, Human; Influenza in Birds
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this research study is to compare how the body reacts to different strengths
      of an experimental cell culture-grown whole virus A/H5N1 flu vaccine when given with or
      without the addition of aluminum hydroxide adjuvant. Researchers will also look at how much
      antibody is made to the influenza virus hemagglutinin (HA) after subjects receive the H5N1
      vaccine. Three hundred healthy adults aged 18-40 years will participate for approximately 9
      months, which includes screening. Participants will receive 2 doses of vaccine or placebo
      injected 28 days apart. Participants will have blood samples taken up to 7 times and have 8
      scheduled study visits.
    

Detailed description: 
      This is a phase I, randomized, double-blind, placebo-controlled, dose-ranging clinical trial
      of the safety, reactogenicity, and immunogenicity of intramuscular immunization with
      inactivated, Vero cell-culture derived influenza A/H5N1 vaccine given alone or with aluminum
      hydroxide to healthy young adults. The primary objectives are to determine the dose-related
      safety of an inactivated, cell-culture grown whole virus influenza A/H5N1 vaccine with or
      without aluminum hydroxide adjuvant in healthy adults; to determine the potential for
      aluminum hydroxide to enhance the immune response to inactivated whole virus H5N1 vaccine in
      healthy adults approximately 1 month following receipt of 2 doses of vaccine; and to 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. The primary endpoints are adverse
      event (AE) or serious adverse event (SAE) information (solicited in the clinic and via memory
      aids, concomitant medications, periodic targeted physical assessment, and laboratory safety
      evaluations in a subset of subjects); proportion of subjects in each dose group achieving a
      serum neutralizing antibody titer of greater than or equal to 40 against the influenza A/H5N1
      virus 28 days after receipt of the second dose of vaccine (approximately Day 56); proportion
      of subjects in each dose group achieving a serum hemagglutination inhibition (HAI) antibody
      titer of greater than or equal to 40 against the influenza A/H5N1 virus 28 days after receipt
      of the second dose of vaccine (approximately Day 56); 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; and GMT 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 (approximately Day 56). 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; and GMT 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. Approximately 300 healthy adults, 18-40 years old inclusive, will be enrolled at
      up to 5 sites in the United States for up to 9 months, including the screening period. Two
      doses of vaccine or placebo will be injected into the deltoid muscle approximately 28 days
      apart. The study will be conducted in 2 stages. During Stage 1, 90 subjects will be
      randomized to receive saline placebo or 7.5 micrograms (with or without aluminum hydroxide),
      15 micrograms (with or without aluminum hydroxide), or 45 micrograms (without aluminum
      hydroxide) (6 groups; N=15 per group). Blood for safety evaluations will be obtained from all
      subjects in the Stage 1 cohort at screening, and before and 1 week after each vaccination.
      Subjects in Stage 1 will receive their second vaccinations following review of available
      clinical and laboratory safety data by the Safety Monitoring Committee (SMC). If no
      dose-limiting toxicity or safety-related issues are noted during the week after
      administration of the first dose of vaccine during Stage 1 (based on review of clinical and
      laboratory safety data by the SMC), then Stage 1 subjects will receive a second vaccination.
      A complete Stage 1 safety report will be reviewed by the SMC prior to the enrollment of the
      210 additional subjects in Stage 2 (N=50 per formulation group total). Sera for immune
      assessment of antigen-specific immune responses will be collected from all subjects at
      baseline (Day 0), 1 month after each vaccine dose, and 6 months after the second vaccine
      dose. This study is linked to DMID protocol 07-0022.
    

Intervention name(s): Aluminum hydroxide; Inactivated Vero cell based whole virus influenza A/H5N1; Placebo
Intervention type(s): Biological; Biological; Drug
Intervention description(s): Adjuvant administered with A/H5N1 vaccine dosages 7.5 mcg and 15 mcg.; Inactivated Vero cell-grown, whole virus, influenza A/H5N1 vaccine at dosages 7.5 mcg and 15 mcg of hemagglutinin (HA) per 0.5 mL, each dosage with and without aluminum hydroxide adjuvant; 45 mcg HA/0.5 mL without adjuvant.; Saline injected into the deltoid muscle. 2 identical dosages will be given approximately 28 days apart.
Intervention MeSH terms: Aluminum Hydroxide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: influenza, vaccine, A/H5N1, aluminum hydroxide, Vero cell