A Phase 2 Influenza A Challenge Study Following Oral Administration of an H1N1 HA Ad-Vector Seasonal Flu Vaccine

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).

Inclusion criteria

• Male or female volunteers aged 18 - 49 years, inclusive
• Able to give written informed consent
• Low pre-existing antibodies to the study vaccine
• In general good health (no clinically significant health concerns)
• Safety laboratory normal range or not clinically significant (NCS), with few exceptions
• Body mass index (BMI) between 17 and 35
• Comprehension of the study requirements with ability and willingness to complete all assessments and comply with scheduled visits and contacts
• Female participants must have a negative pregnancy test at screening

Exclusion criteria

• Receipt of any influenza vaccine within two years prior to study
• Use of any investigational vaccine/adjuvanted vaccine within 8 weeks of study
• Use of any investigational drug or device within 4 weeks of study
• Use of any licensed vaccine within 30 days of study
• Presence of significant uncontrolled medical or psychiatric illness within 3 months of study
• Clinically significant and/or protocol defined ECG abnormality
• Positive serology for HIV-1 or HIV-2, or HBsAg or HCV antibodies
• Cancer, or treatment for cancer, within 3 years of study
• History of drug, alcohol or chemical abuse within 1 year
• Receipt of blood or blood products within 6 months of study
• Donation of blood within 4 weeks of study
• Presence of a fever ≥ 38ºC measured orally at baseline
• Stool sample with occult blood at screening
• Positive urine drug screen for drugs of abuse at screening
• Positive breath or urine alcohol test at screening or baseline
• Consistent/habitual smoking within 2 months prior to vaccination
• History of serious reactions to any vaccination such as anaphylaxis, respiratory problems, Guillain-Barre syndrome, hives or abdominal pain
• Asthma, bronchiectasis or chronic obstructive pulmonary disease
• Any known allergy or intolerance to oseltamivir