Flublok or Fluzone With Advax-CpG55.2 or AF03
Condition: Influenza; Influenza Immunisation
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a Phase I, randomized, double blinded, clinical trial in up to 240 males and
      non-pregnant females, 18-45 years of age, inclusive, who are in good health and meet all
      eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity
      and immunogenicity of either the 2018/2019 seasonal Fluzone or Flublok Quadrivalent Influenza
      Vaccine (QIV) manufactured by Sanofi Pasteur (SP) given without adjuvant or with one of two
      adjuvant formulations, AF03 or Advax-CpG55.2. Eight Vaccine and Treatment Evaluation Unit
      (VTEU) sites will be included in the study. Study duration is approximately 18 months, and
      subject participation duration is 12 months. The primary objectives of this study are: 1) to
      assess the safety and reactogenicity of 2018/2019 Fluzone and Flublok with and without AF03
      or Advax-CpG55.2 adjuvant; 2) to assess the serum hemagglutination inhibition (HAI) antibody
      responses against 2018/2019 QIV strains from baseline (Day 1) to approximately Day 29 after
      receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 3)
      to assess the serum neuraminidase inhibition antibody (NAI) responses by enzyme-linked lectin
      assay (ELLA) against NA antigens in the 2018/2019 QIV from baseline (Day 1) to approximately
      Day 29 after receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2
      adjuvant; 4) to assess the influenza neutralizing (Neut) antibody titer responses against
      2018/2019 QIV strains from baseline (Day 1) to approximately Day 29 after receipt of
      2018/2019 Fluzone and Flublok with and without AF03 or Advax- CpG55.2 adjuvant.
    

Detailed description: 
      This is a Phase I, randomized, double blinded, clinical trial in up to 240 males and
      non-pregnant females, 18-45 years of age, inclusive, who are in good health and meet all
      eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity
      and immunogenicity of either the 2018/2019 seasonal Fluzone or Flublok Quadrivalent Influenza
      Vaccine (QIV) manufactured by Sanofi Pasteur (SP) given without adjuvant or with one of two
      adjuvant formulations, AF03 or Advax-CpG55.2. Subjects will be stratified by prior receipt of
      licensed, seasonal influenza vaccine (defined as receipt of at least one of the 2017/2018
      and/or 2018/2019 influenza vaccines) and will be randomly assigned to 1 of 6 treatment arms
      to receive a single dose of one of the two seasonal 2018/2019 QIV vaccine formulations with
      or without one of the two adjuvants (Day 1). On approximately Day 90, each subject will
      receive a single dose of the seasonal 2019/2020 QIV. Groups 1, 2 and 3 will receive 2019/2020
      Fluzone QIV and Groups 4, 5 and 6 will receive 2019/2020 Flublok QIV. Eight Vaccine and
      Treatment Evaluation Unit (VTEU) sites will be included in the study. Study duration is
      approximately 18 months, and subject participation duration is 12 months. The primary
      objectives of this study are: 1) to assess the safety and reactogenicity of 2018/2019 Fluzone
      and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 2) to assess the serum
      hemagglutination inhibition (HAI) antibody responses against 2018/2019 QIV strains from
      baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with
      and without AF03 or Advax-CpG55.2 adjuvant; 3) to assess the serum neuraminidase inhibition
      antibody (NAI) responses by enzyme-linked lectin assay (ELLA) against NA antigens in the
      2018/2019 QIV from baseline (Day 1) to approximately Day 29 after receipt of 2018/2019
      Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 4) to assess the
      influenza neutralizing (Neut) antibody titer responses against 2018/2019 QIV strains from
      baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with
      and without AF03 or Advax- CpG55.2 adjuvant. The secondary objectives of this study are: 1)
      to assess protocol specified adverse events of special interest (AESI), medically-attended
      adverse events (MAAEs), including new-onset chronic medical conditions (NOCMCs) and
      potentially immune-mediated medical conditions (PIMMCs) that occur after receipt of study
      product; 2) to assess the HAI, Neut and NAI ELLA responses to the 2019/2020 QIV strains prior
      to (Day 1) and approximately 28 days after vaccination with the 2019/2020 QIV in all study
      groups; 3) to assess the HAI antibody responses against heterologous influenza A/H1 and H3
      strains from baseline (Day 1) to approximately Days 8, 29, 57, 90 and 118 after receipt of
      2018/2019 Fluzone or Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 4) to assess
      NAI ELLA responses against heterologous N1 and N2 NA antigens from baseline (Day 1) to
      approximately Days 8, 29, 57, 90 and 118 after administration of 2018/2019 Fluzone with and
      without AF03 or Advax-CpG55.2 adjuvant; 5) to assess the influenza neutralizing (Neut)
      antibody titer responses against heterologous influenza A/H1 and H3 strains from baseline
      (Day 1) to approximately Days 8, 29, 57, 90 and 118 after administration of 2018/2019 Fluzone
      and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 6) to assess the longitudinal
      kinetics and durability of the HAI, NAI, and Neut responses against the 2018/2019 QIV strains
      on approximately Days 8, 57, 90 and 118 following receipt of the 2018/2019 Fluzone and
      Flublok with and without AF03 or Advax-CpG55.2 adjuvant.
    

Intervention name(s): AF03; Delta Inulin-CpG55.2; Influenza Virus Quadrivalent Inactivated Vaccine; Quadrivalent Recombinant Seasonal Influenza Vaccine
Intervention type(s): Drug; Biological; Biological; Biological
Intervention description(s): A squalene-in-PBS emulsion stabilized by nonionic surfactants, sorbitan oleate and macrogol cetostearyl ether; A combination adjuvant supplied as two separate components, Delta Inulin (Sypharma Pty Ltd.) and CpG55.2 (Nikko Denka Avecia and Sypharma Pty Ltd); 2018/2019 Fluzone QIV and 2019/2020 Fluzone QIV vaccines will be given with 90 days interval; 2018/2019 Flublok QIV and 2019/2020 Flublok QIV vaccines will be given with 90 days interval
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Immunogenicity; Influenza; Influenza Vaccine; Phase 1; Quadrivalent; Safety