H5N8 Mix and Match With or Without AS03 or MF59 in Healthy Adults: Immunology
Condition: Avian Influenza
MeSH terms: Influenza, Human; Influenza in Birds
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a Phase I cohort-randomized, double-blind, controlled trial designed to assess the
      safety, reactogenicity, and immunogenicity of a monovalent inactivated influenza A/H5N8 virus
      vaccine administered at different dosages (3.75 and 15 mcg of HA per dose) given with or
      without AS03 or MF59 adjuvants. This study will be conducted at 6 sites and enroll 150 (up to
      380) males and non-pregnant females, 19 to 64 years old, inclusive who are in good health and
      meet all eligibility criteria. The entire study duration is approximately 24 months and each
      subject participation duration is approximately 13 months. The primary objectives are: 1) To
      assess the safety and reactogenicity of a monovalent inactivated influenza A/H5N8 virus
      vaccine following receipt of two doses administered intramuscularly at different dosages
      (3.75 and 15 mcg of HA per dose) given with or without AS03 or MF59 adjuvants approximately
      21 days apart. 2) To assess the serum HAI and Neut antibody responses to a monovalent
      inactivated influenza A/H5N8 virus vaccine following receipt of two doses administered
      intramuscularly at different dosages (3.75 and 15 mcg of HA per dose) given with or without
      AS03 or MF59 adjuvants approximately 21 days apart.
    

Detailed description: 
      This is a Phase I cohort-randomized, double-blind, controlled trial designed to assess the
      safety, reactogenicity, and immunogenicity of a monovalent inactivated influenza A/H5N8 virus
      vaccine manufactured by bioCSL administered at different dosages (3.75 and 15 mcg of HA per
      dose) given with or without AS03 or MF59 adjuvants manufactured by GlaxoSmithKline
      Biologicals (GSK) and Novartis Vaccines and Diagnostics (NVD), respectively. This study will
      be conducted at 6 VTEU sites and enroll 150 (up to 380) males and non-pregnant females, 19 to
      64 years old, inclusive who are in good health and meet all eligibility criteria. The entire
      study duration is approximately 24 months and subject participation duration is approximately
      13 months. Subjects will be enrolled in one of two cohorts, and within each cohort subjects
      will be randomized in a 2:2:1 ratio. Subjects in Cohort 1 will be randomly assigned to 1 of 3
      treatment arms to receive two doses of the A/H5N8 vaccine at varying antigen dosages (3.75 or
      15 mcg HA) with AS03 (30-76 subjects per treatment arm), or to a comparator arm receiving two
      doses of the A/H5N8 vaccine (15 mcg HA) without adjuvant (15-38 subjects). Subjects in Cohort
      2 will be randomly assigned to 1 of 3 treatment arms to receive two doses of the A/H5N8
      vaccine at varying antigen dosages (3.75 or 15 mcg HA) with MF59 (30-76 subjects per
      treatment arm), or to a comparator arm receiving two doses of the A/H5N8 vaccine (15 mcg HA)
      without adjuvant (15-38 subjects). All subjects will receive the same dosage of vaccine with
      or without the same adjuvant at both of their first and second study vaccinations, with the
      exception that subjects in Cohort 1 who do not receive Vaccination 2 prior to February 28,
      2017 will receive a second unadjuvanted vaccination with the same antigen dosage as their
      randomized assignment. All doses will be administered intramuscularly approximately 21 days
      apart. Primary objectives are: 1) To assess the safety and reactogenicity of a monovalent
      inactivated influenza A/H5N8 virus vaccine following receipt of two doses administered
      intramuscularly at different dosages (3.75 and 15 mcg of HA per dose) given with or without
      AS03 or MF59 adjuvants approximately 21 days apart. 2) To assess the serum HAI and Neut
      antibody responses to a monovalent inactivated influenza A/H5N8 virus vaccine following
      receipt of two doses administered intramuscularly at different dosages (3.75 and 15 mcg of HA
      per dose) given with or without AS03 or MF59 adjuvants approximately 21 days apart. Secondary
      objectives are: 1) To assess study unsolicited non-serious AEs following receipt of two doses
      of a monovalent inactivated influenza A/H5N8 virus vaccine administered intramuscularly at
      different dosages (3.75 and 15 mcg of HA per dose) given with or without AS03 or MF59
      adjuvants approximately 21 days apart. 2) To assess medically-attended adverse events
      (MAAEs), including new-onset chronic medical conditions (NOCMCs), potentially immune-mediated
      medical conditions (PIMMCs), and all serious adverse events (SAEs) following receipt of two
      doses of a monovalent inactivated influenza A/H5N8 virus vaccine administered intramuscularly
      at different dosages (3.75 and 15 mcg of HA per dose) given with or without AS03 or MF59
      adjuvants approximately 21 days apart. 3) To assess the serum HAI and Neut antibody responses
      to a monovalent inactivated influenza A/H5N8 virus vaccine following receipt of one dose
      administered intramuscularly at different dosages (3.75 and 15 mcg of HA per dose) given with
      or without AS03 or MF59 adjuvants.
    

Intervention name(s): AS03; MF59 adjuvant; Monovalent Influenza A/H5N8 vaccine
Intervention type(s): Drug; Drug; Biological
Intervention description(s): AS03 oil-in-water emulsion adjuvant.; Microfluoridized adjuvant 59 (MF59) is an oil-in-water emulsion.; Monovalent inactivated influenza A/H5N8 virus vaccine for IM injection. prepared from influenza virus propagated in chicken egg fluid using seed virus prepared from the candidate vaccine virus (CVV), influenza virus A/gyrfalcon/Washington/41088-6/2014(H5N8)-PR8-IDCDC-RG43A (abbreviated as IDCDC-RG43A).
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: A/H5N8; Adjuvants; AS03; Inactivated; Influenza; MF59; Monovalent