Booster Trial to 07-0019 With A/Anhui/05 With and Without MF59
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1

Summary: 
      This research will study safety and the body's immune (defense system) responses, including
      anti-H5 flu antibodies (the body's protective proteins found in the blood), to an inactivated
      influenza "H5" bird flu, virus vaccine. Participants will be assigned by chance to receive
      the vaccine injections with and without an adjuvant, (substance that can improve vaccine
      effectiveness so less vaccine may be used) MF59, or placebo (inactive substance). Five
      different vaccine dose strengths will be evaluated. About 735 healthy participants, ages
      18-49 will be asked to take part in this study. Study procedures include physical exam, blood
      sampling, and use of a memory aid. Volunteers will participate for up to 13 months.
    

Detailed description: 
      Severe disease in humans due to avian influenza viruses of the H5N1 subtype has raised
      considerable concern regarding the potential emergence of these viruses in pandemic form.
      Planning for control of such pandemics is of vital importance, and a cornerstone of this
      planning is the development of effective vaccines for H5N1. This study is designed to gather
      critical information on the safety, tolerability, and immunogenicity of booster vaccination
      with influenza A/Anhui/05 with and without the adjuvant MF59 in subjects previously primed
      with the clade 1 vaccine or unprimed individuals. Primary objectives are: to evaluate booster
      vaccination with a different variant/clade of A/Anhui/05 vaccine to assess possible prime for
      a broad immune response by 1 or 2 previous doses of A/Vietnam/1203/04; to compare 1-dose
      versus 2-dose priming of A/Vietnam/1203/04 followed by heterologous boosting with A/Anhui/05;
      to assess the safety of MF59 adjuvanted A/Anhui/05 vaccine in primed subjects; and to compare
      safety and immunogenicity of 1 and 2 doses of A/Anhui/05 with or without MF59 adjuvant, or to
      saline placebo, in a Phase I dose response study in naïve subjects. Up to 180 healthy adult
      subjects aged 18 through 49 (Subjects previously enrolled in 07-0019 will be eligible for
      08-0013 even if they are older than 49 years of age at the time of enrollment into 08-0013.)
      who were previously enrolled in Division of Microbiology and Infectious Diseases (DMID)
      07-0019 and received either 1 or 2 priming doses of A/Vietnam/1203/04 H5 influenza vaccine
      will be enrolled in this study. Additionally, approximately 555 healthy adult subjects aged
      18 through 49 H5 vaccine naïve will be recruited to receive 2 doses, 28 days apart, of
      A/Anhui/05 vaccine with or without MF59 adjuvant or placebo. Entry criteria for the newly
      enrolled subjects will be the same as those used in DMID 07-0019. Because extensive safety
      data were collected for similar H5 vaccines, subjects will not be screened with clinical
      laboratory tests. The booster for Groups 8-9 will be randomized to 1 of 2 possible doses,
      with approximately 20 subjects per Group (allocation ratio 1:1) in each dose assignment: 3.75
      micrograms (mcg) MF59, or 3.75 mcg. Newly enrolled, vaccine naïve subjects in Group 10 will
      be randomized to 1 of 9 possible dosages with or without MF59 adjuvant, with approximately 50
      subjects in each dosage assignment: 3.75 mcg MF59, 3.75 mcg, 7.5 mcg MF59, 7.5 mcg, 15.0 mcg
      MF59, 15.0 mcg, 45.0 mcg MF59, 45.0 mcg, 90 mcg, or saline placebo with 3 groups of 35
      subjects each, receiving different volumes of: one injection of 0.5 mL, one injection of 0.75
      mL or 2 injections of 0.75 mL, for comparison. Volunteers will be observed in the clinic for
      at least 20 minutes after vaccination, and will maintain a Memory Aid to record oral
      temperature and systemic and local adverse events (AEs) and serious adverse events (SAEs) for
      8 days after vaccination. Volunteers will be contacted by telephone 1 to 3 days after
      vaccination (approximately Day 2 post dose) to assess for the occurrence of AEs/SAEs, and
      they will return to the clinic 7 to 9 days after vaccination for AE/SAE and concomitant
      medication assessment, a targeted physical examination (if indicated), and review of the
      Memory Aid. Volunteers in Group 10 will return to clinic on Day 28 for review of eligibility
      criteria to receive Dose Number 2 of A/Anhui/05 or placebo. Volunteers in this group will
      then follow the same study schedule as following the first vaccination. All subjects will
      continue to be followed for 12 months after the last vaccination. It is anticipated that this
      study will enroll up to 735 subjects over 10-14 weeks. This
    

Intervention name(s): MF-59; A/Anhui/05; Placebo
Intervention type(s): Biological; Biological; Drug
Intervention description(s): Doses of A/Anhui/05 vaccine (A) will be administered with or without MF59 adjuvant.; Monovalent inactivated surface antigen influenza A/H5N1 (modified Hemagglutinin and Neuraminidase of A/Anhui/01/2005) vaccine supplied in 5mL multi-dose vials with thimerosal [0.01%(w/v)] as a preservative. Each dose level includes both unadjuvanted and MF59C.1 adjuvanted formulations: 7.5, 15, 30, or 60 micrograms (mcg) of H5 Hemagglutinin per milliliter (mL) with MF59C.1, and 7.5, 15, 30, or 60 micrograms (mcg) of H5 Hemagglutinin per milliliter (mL) without MF59C.1 adjuvant.; Sterile normal saline for injection (0.9% Sodium Chloride Injection, USP Preservative-Free).
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Influenza, H5N1, vaccine, avian influenza