A Phase 2 Influenza A Challenge Study Following Oral Administration of an H1N1 HA Ad-Vector Seasonal Flu Vaccine
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 2

Summary: 
      A Phase 2 Randomized, Placebo- and Active-Controlled, Human Influenza A/California/04/2009
      (H1N1) Challenge Study Following Administration of an Oral H1N1 Hemagglutinin (HA)
      Adenoviral-Vector Based Seasonal Influenza Vaccine and dsRNA Adjuvant (VXA-A1.1) to Healthy
      Adult Volunteers.
    

Detailed description: 
      This is a Phase 2 randomized, placebo- and active-controlled, two-part study in which healthy
      adult volunteers with low or undetectable pre-existing antibodies against
      A/California/7/2009(H1N1) pdm09-like virus will be challenged with an influenza A/H1N1 human
      challenge strain approximately 90 days after vaccination with a single dose of H1N1 HA
      Adenoviral-vector based seasonal influenza vaccine and dsRNA adjuvant (VXA-A1.1), an
      injectable QIV vaccine, and/or placebo.

      An independent Safety Monitoring Committee (SMC) will oversee the safety of the study.

      To accommodate the limited size of the isolation unit that will be utilized for the challenge
      and post-challenge sequestration period, subjects will move through the study (enrollment,
      vaccination and challenge) sequentially in a total of 6 cohorts. Each cohort will randomize
      30 subjects to obtain approximately 25 subjects per cohort for the challenge phase. Subjects
      will be randomized in a ratio of 2:2:1 (VXA-A1.1: Quadrivalent Influenza Vaccine (QIV):
      Placebo.

      The study will be conducted in two parts.

      Part A: Subjects will be randomized in a double-blinded manner to receive a single
      administration of one of three treatment arms:

        -  Arm 1: VXA-A1.1 oral vaccine + placebo Intramuscular (IM)

        -  Arm 2: QIV (IM) injection + oral placebo

        -  Arm 3: Placebo IM injection + oral placebo

      Subjects will return to the site for ~8 visits and be contacted remotely at defined time
      points to be followed for immunogenicity and safety during study Part A.

      Part B: Subjects will be challenged with a wild-type influenza A H1 virus strain ~90 days
      following vaccination. Blood samples will be collected to evaluate immunogenicity. Subjects
      will remain in the isolation unit for 6 to 9 days post-challenge.

      Following challenge, influenza symptoms and signs will be assessed during the sequestration
      period. Blood samples and nasopharyngeal swab samples will be collected. Vital signs will be
      measured every 4 hours during waking hours.

      After release from the isolation unit subjects will return to the site 30 days
      post-challenge. Part B will continue for purposes of collecting long term safety follow-up
      (serious adverse events (SAEs), AEs of special interest (AESIs) and any new onset of chronic
      illness (NOCI) via phone contacts through 1 year post-vaccination (Day 365).
    

Intervention name(s): VXA-A1.1; Fluzone®; Placebo Tablets; Saline Solution for Placebo IM Injection
Intervention type(s): Biological; Biological; Other; Other
Intervention description(s): Enteric coated oral vaccine tablet; Fluzone Quadravalent (Fluzone®) influenza vaccine (QIV) suspension for intramuscular (IM) injection; Placebo tablets similar in size, color and number to the active oral tablet vaccine drug product
Other intervention name(s): Oral H1N1 Ad5 Tableted Vaccine; Fluzone Quadravalent; Enteric Coated Placebo Tablets; 0.9% Sodium Chloride Injection, USP
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Oral vaccination followed by viral challenge at 3 months post vaccination
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Challenge; oral vaccine