A Safety and Immunogenicity Study of IVACFLU-A/H5N1
Condition: Avian Influenza
MeSH terms: Influenza, Human; Influenza in Birds
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The study hypothesis was that two 0.5 mL doses of whole virion monovalent A/H5N1 influenza
      vaccine (IVACFLU-A/H5N1) adjuvanted with alum would be safe and well tolerated in healthy
      adults, and that at least one of the two doses tested would be immunogenic in 60% or more of
      the subjects tested.
    

Detailed description: 
      Although the A/H1N1 (2009) pandemic has subsided and the virus has become endemic, the threat
      of another pandemic due to avian influenza A/H5N1 remains constant. Since 1997, highly
      pathogenic A/H5N1 avian viruses have caused both widespread outbreaks in poultry with high
      mortality and sporadic, severe, and fatal disease in humans. Southeast Asian countries,
      including Vietnam, have been affected by influenza A/H5N1. From 2003 through March 2015, WHO
      has reported 826 confirmed human cases of A/H5N1 influenza infection; including 440 fatal
      cases (World Health Organization, 2015). Southeast Asian countries accounted for 42% of all
      confirmed influenza A/H5N1 cases reported since 2003, and influenza A/H5N1 infection in
      animals is now thought to be endemic in the region (World Health Organization, 2015). As of
      March 2015, Vietnam has reported 127 confirmed human cases and 64 deaths. In 2014, two cases
      of A/H5N1 avian influenza were reported in Vietnam. Therefore, the risk of transmission to
      human is still present.

      At the time of the study, no influenza A/H5N1 vaccine had been licensed in Vietnam.
      IVACFLU-A/H5N1 is an influenza A/H5N1 vaccine produced by Institute of Vaccines and Medical
      Biologicals (IVAC) using embryonated chicken eggs. IVACFLU-A/H5N1 is a whole virus vaccine,
      collected in a linear sucrose density gradient solution using a continuous flow centrifuge
      (Alfa Wassermann, West Caldwell, NJ) and inactivated with formaldehyde. The vaccine is alum
      adjuvanted. Vaccine strain NIBRG-14 derived from original influenza A/Vietnam/1194/2004 was
      provided to IVAC by the National Institute for Biological Standards and Control of the Health
      Protection Agency of the United Kingdom. A clinical trial of IVACFLU-A/H5N1 vaccine conducted
      in 75 subjects at the Ben Luc Health District in Vietnam in 2014 showed that the vaccine is
      safe and immunogenic at doses of 7.5 and 15 mcg.

      This study was conducted in two stages: Phase 2 was a dose selection study where subjects
      were randomized to one of the three groups (15 mcg IVACFLU-A/H5N1 vaccine, 30 mcg
      IVACFLU-A/H5N1 vaccine or placebo) at a 1:1:1 ratio. The conduct of Phase 3 was dependent on
      showing hemagglutination inhibition (HAI) response titer of ≥1:40 in ≥60% of vaccine
      recipients in at least one of the two Phase 2 IVACFLU-A/H5N1 vaccine groups. Based on the
      review of immunogenicity and safety results from the Phase 2 study, a dose of study vaccine
      was selected for Phase 3. Subjects were randomized at two sites (Khanh Hoa and Hai Phong) to
      receive the IVACFLU-A/H5N1 vaccine dose selected in Phase 2 or placebo . Safety was assessed
      in all subjects and immunogenicity was measured in a subset of subjects at the Hai Phong
      study site.
    

Intervention name(s): IVACFLU-A/H5N1 vaccine; Placebo
Intervention type(s): Biological; Biological
Intervention description(s): Monovalent A/H5N1 influenza vaccine (MIV), whole virion inactivated, purified by sucrose gradient on ultracentrifuge. The vaccine was produced in eggs, inactivated with formaldehyde, and formulated with aluminum hydroxide 0.6 mg/0.5 mL with no preservative.; Includes 4.500mg sodium chloride, 0.685 mg sodium phosphate dibasic dihydrate, and 0.186 mg sodium phosphate monobasic dihydrate.
Other intervention name(s): Sterile Phosphate Buffered Saline (PBS)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Avian Influenza; A/H5N1 vaccine; IVAC