A Phase I Study Priming With an Inactivated A/H7N9 Influenza Virus Vaccine With or Without MF59 Adjuvant Followed by Live Attenuated A/H7N9 Influenza Virus Vaccine
Condition: Avian Influenza; Immunisation
MeSH terms: Influenza, Human; Influenza in Birds
Study type: Interventional
Phase: Phase 1

Summary: 
      A phase I prospective, randomized study in healthy adult subjects at a single center. Adult
      subjects age 18 to 47 years and meeting all enrollment criteria will choose to participate as
      subjects who receive inactivated vaccine followed by a live vaccine boost at 4 weeks (Group
      1), 12 weeks (Group 2), or 24 weeks (Group 3), or to be in an observational group (Group 4)
      which will not be scheduled for a booster dose but may serve as a roll-over group for
      subjects who withdraw prior to the second vaccination but agree to remain in follow-up. A
      fifth group will receive two intramuscular doses of adjuvanted H7N9 pIIV separated by four
      weeks. The primary objectives of this study are to (1) assess the safety of H7N9 pLAIV
      administered to individuals who have previously received MF59-adjuvanted or unadjuvanted H7N9
      pIIV, (2) evaluate the ability of a single dose of unadjuvanted H7N9 pIIV to prime for
      enhanced immunogenicity (booster response) to subsequent administration of
      antigenically-matched H7N9 pLAIV vaccine, and to (3) evaluate the ability of a single dose of
      MF59-adjuvanted H7N9 pIIV to prime for enhanced immunogenicity (booster response) to
      subsequent administration of antigenically-matched H7N9 pLAIV vaccine.
    

Detailed description: 
      The study will be conducted as a Phase I prospective, randomized study in healthy adult
      subjects at a single center. Adult subjects age 18 to 47 years and meeting all enrollment
      criteria will choose to participate as subjects who receive unadjuvanted or adjuvanted H7H9
      pIIV vaccine followed by a live vaccine boost at 4 weeks (Group 1, n=24), 12 weeks (Group 2,
      n=24), or 24 weeks (Group 3, n=24), or to be in an observational group (Group 4, n=16) which
      will not be scheduled for a booster dose but may serve as a roll-over group for subjects who
      withdraw prior to the second vaccination but agree to remain in follow-up. Within each group,
      subjects will be randomized at a 1:1 ratio to receive a single dose of either unadjuvanted
      H7N9 pIIV at 15 mcg (Subgroup A), or the same vaccine adjuvanted with the oil-in-water
      emulsion, MF59, (Subgroup B) delivered intramuscularly. Finally, a fifth group (Group 5,
      n=12) will receive two intramuscular doses of adjuvanted H7N9 pIIV separated by four weeks.
      The total duration of study participation for all subjects will be approximately 13 months.
      Recruitment, enrollment and administration of study product will be suspended when one of the
      following occurs in the clinical or research laboratory at the clinical site: at least two
      respiratory cultures or PCR assays are determined to be positive for influenza or at least
      10% diagnostic tests (rapid tests, respiratory cultures or PCR assays) performed for
      influenza as positive during two consecutive weeks in the clinical or research laboratory at
      the clinical site. Recruitment, enrollment and administration of study product may be resumed
      after 2 weeks without a signal that influenza is still circulating in the community, as
      defined by the same measures that indicate the start of influenza season (i.e., less than 2
      respiratory cultures or PCR assays are determined to positive for influenza or less than 10%
      of diagnostic tests performed or influenza with positive results). The primary objectives of
      this study are to (1) assess the safety of H7N9 pLAIV administered to individuals who have
      previously received MF59-adjuvanted or unadjuvanted H7N9 pIIV, (2) evaluate the ability of a
      single dose of unadjuvanted H7N9 pIIV to prime for enhanced immunogenicity (booster response)
      to subsequent administration of antigenically-matched H7N9 pLAIV vaccine, and to (3) evaluate
      the ability of a single dose of MF59-adjuvanted H7N9 pIIV to prime for enhanced
      immunogenicity (booster response) to subsequent administration of antigenically-matched H7N9
      pLAIV vaccine. The secondary objectives of this study are to (1) assess the safety of priming
      with MF59-adjuvanted H7N9 pIIV or unadjuvanted H7N9 pIIV, (2) assess the immune response in
      subjects vaccinated with a single dose of MF59-adjuvanted H7N9 pIIV or a single dose of
      unadjuvanted H7N9 pIIV, and to (3) compare the booster effect seen after intervals of 4
      weeks, 12 weeks, or 24 weeks within each priming group.
    

Intervention name(s): Influenza Virus Vaccine, Live Attenuated H7N9 Anhui 2013/AA ca; Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013; MF59 adjuvant
Intervention type(s): Biological; Biological; Drug
Intervention description(s): MedImmune supplies pLAIV vaccines as a colorless to pale yellow and clear to slightly cloudy suspension in single, unit-dose, Becton-Dickinson Accuspray™ Nasal Spray Systems sprayer devices. Each filled sprayer device contains a 0.5 mL dose of 10^7FFU of H7N9 Anhui 2013/AA ca vaccine. Group I receives the IN dose on Day 29, Group 2 on Day 85, and Group 3 on Day 169.; Sanofi supplies the monovalent influenza A/H7N9 virus vaccine as a sterile, clear, and slightly opalescent suspension in single-dose vials containing 15 mcg HA per 0.5 mL. Group 1 through Group5 will receive the IM vaccine on Day 1; Novartis supplies the MF59 adjuvant as an oil-in-water milky emulsion in single-use vials containing a fill volume of 0.7 mL. Group 1 through Group 5 will receive MF59 IM on Day 1.
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: H7N9 pandemic; inactivated influenza vaccine (pIIV); live attenuated influenza vaccine (pLAIV); MF59 adjuvant