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.
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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
637
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).
Emory Children's Center - Pediatric Infectious Diseases
Atlanta, Georgia, United States
Emory University School of Medicine - Emory Children's Center - Pediatric Infectious Diseases
Atlanta, Georgia, United States
University of Iowa - Infectious Disease Clinic
Iowa City, Iowa, United States
University of Maryland School of Medicine - Center for Vaccine Development - Baltimore
Baltimore, Maryland, United States
Mayo Clinic, Rochester - Vaccine Research Group
Rochester, Minnesota, United States
Saint Louis University - Center for Vaccine Development
St Louis, Missouri, United States
Duke Translational Medicine Institute - Clinical Vaccine Unit
Durham, North Carolina, United States
Vanderbilt University - Pediatric - Infectious Diseases
Nashville, Tennessee, United States
University of Texas Medical Branch - Pediatrics - Infectious Diseases and Immunology - Galveston
Galveston, Texas, United States
Group Health Research Institute - Seattle
Seattle, Washington, United States
Geometric Mean Titer, frequency of 4-fold or greater antibody titer increases, and proportion of subjects achieving a serum HAI antibody titer of 1:40 or greater against the 2 antigens being evaluated, A/Vietnam/1203/04 and A/Anhui/05 H5N1 virus.
Time frame: 1 month and 6 months after last vaccination.
Local and systemic adverse event (AE) or serious adverse event (SAE) information (solicited in-clinic and via memory aids, concomitant medications, and periodic targeted physical assessments).
Time frame: Duration of study.
Geometric mean titer in primed versus unprimed subjects to A/Vietnam/1203/04 and A/Anhui/05.
Time frame: Days 8 and 14 post-vaccination.
Geometric mean titer (GMT), frequency of 4-fold or greater increases and proportion of subjects achieving a titer of 1:40 or greater in neutralizing antibody titers against the two antigens being evaluated, A/Vietnam/1203/04 and A/Anhui/05 H5N1 virus.
Time frame: 1 month and 6 months after last vaccination.
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