Phase 2 Randomized, Controlled, Human Influenza A (H1N1) Challenge Study Following Administration of an Oral H1N1 HA Adenoviral-Vector Based Seasonal Influenza Vaccine and dsRNA Adjuvant to Healthy Adult Volunteers
Phase: PHASE2
Conditions: Influenza
Sponsor: Vaxart

STUDY TITLE 
A Phase 2 Randomized, Placebo- and Active-Controlled, Human Influenza 
A/California/04/2009 (H1N1) Challenge Study Following Administration of an Oral 
H1N1 HA Adenoviral-Vector Based Seasonal Influenza Vaccine and dsRNA Adjuvant 
(VXA-A1.1) to Healthy Adult Volunteers 
 
Protocol Number:   
 
VXA-CHAL-201 
 
Phase: 
2 
 
Investigational Product: 
 
Indication 
VXA-A1.1 Oral Vaccine 
 
Prevention of Seasonal Influenza  
 
Sponsor: 
 
Vaxart, Inc. 
385 Oyster Point Blvd, Suite 9A 
South San Francisco, California 94080 
 
 
 
Sponsor Contact: 
Shaily Jaini Garg, PMP, CCRA 
Vice President, Clinical Development & Regulatory Affairs 
Vaxart, Inc. 
P:  650-521-4496; email:  sgarg@vaxart.com 
 
 
Sponsor Chief Medical Officer: 
Dave Liebowitz, MD, PhD 
Chief Medical Officer 
Vaxart, Inc. 
P:  408-340-8605; email:  dliebowitz@vaxart.com 
Study Medical Monitor: 
Michelle Abada, MD 
Study Medical Monitor 
WCCT Medelis, Inc. 
P: (714) 252-0700 Ext 1068; email: 
Michelle.Ababa@wcct.com 
 
 

Protocol VXA-CHAL-201 
VXA-A1.1 Vaccine 
08 June 2017 (Amend. 3) 
-CONFIDENTIAL- 
2 
Protocol Date and Version: 
 
 
   Replaces: 
 
June 8, 2017 (Amendment 3) 
September 27, 2016 (Amendment 2) 
July 27, 2016 (Amendment 1) 
June 28, 2016 (Original)  
 
 
 
 
Note of Confidentiality:  The information contained in this clinical protocol or arising during the study are 
proprietary and confidential and may not be disclosed without the expressed, written consent of Vaxart Inc. 
 
 

Protocol VXA-CHAL-201 
VXA-A1.1 Vaccine 
08 June 2017 (Amend. 3) 
-CONFIDENTIAL- 
3 
INVESTIGATOR’S STATEMENT 
 
I agree to conduct the study as outlined in the Protocol entitled: 
 
A Phase 2 Randomized, Placebo- and Active-Controlled, Human Influenza 
A/California/04/2009 (H1N1) Challenge Study Following Administration of an Oral 
H1N1 HA Adenoviral-Vector Based Seasonal Influenza Vaccine and dsRNA Adjuvant 
(VXA-A1.1) to Healthy Adult Volunteers 
Amendment 3 
  
in accordance with the guidelines and all applicable government regulations (21 CFR 50, 54, 
56, 312; ICH E6), and the Declaration of Helsinki.  I have read and understand all sections of 
the protocol, including Section 9, Administrative Items, and the Investigator’s Brochure. 
I will provide copies of the protocol and all pertinent information to all individuals responsible 
to me who assist in the conduct of this clinical trial.  I will discuss this material with them to 
ensure that they are fully informed regarding the investigational vaccine and the conduct of the 
study. 
I understand that Vaxart, its representatives, and regulatory agencies, shall have access to any 
source documents relevant to this study including documents that demonstrate protocol and 
regulatory compliance. 
 
 
 
 
 
 
Investigator Printed Name 
 
Signature 
 
Date 
 

VXA-CHAL-201 
VXA-A1.1 Vaccine 
08 June 2017 (Amend. 3) 
CONFIDENTIAL 
4 
STUDY 
NUMBER 
VXA-CHAL-201   (NCT: 02918006)  
STUDY TITLE 
A Phase 2 Randomized, Placebo- and Active-Controlled, Human Influenza 
A/California/04/2009 (H1N1) Challenge Study Following Administration of an Oral 
H1N1 HA Adenoviral-Vector Based Seasonal Influenza Vaccine and dsRNA 
Adjuvant (VXA-A1.1) to Healthy Adult Volunteers  
SPONSOR 
Vaxart, Inc. 
PHASE 
2 
STUDY POPULATION 
180 healthy adult volunteers age 18 to 49 years 
(~180 subjects will be vaccinated in Part A to ensure at least 150 subjects are available to 
participate in the challenge phase in Part B)   
NO. OF SITES 
1 qualified U.S. Site (with isolation unit) 
DURATION  
OF STUDY 
PARTICIPATION 
One year following successful pre-screening, screening and enrollment, to include: 
•
PART A: Vaccination and initial safety follow-up phase (Study Day 1 – Day 90)
•
PART B: Influenza challenge phase (Study Day 90) and long-term safety follow-up
(through Day 365 post-vaccination).
Enrollment, vaccination, challenge and follow-up visits will be staggered into approximately  
6 cohorts of subjects enrolled at approximately 30-day intervals. Individual subject involvement 
in study activities is estimated to last ~16 months. 
INVESTIGATIONAL 
VACCINE 
VXA-A1.1 is an E1/E3-deleted replication-defective Adenovirus serotype 5 vaccine vector 
for prevention of seasonal influenza H1N1. The vaccine vector encodes for a full-length 
hemagglutinin (HA) gene from the influenza A/California/04/2009 (H1N1) and a double-
stranded RNA (dsRNA) adjuvant (TLR3 agonist). The adjuvant is a short hairpin RNA, 
expressed as a 21 nucleotide sequence as a tandem sequence in forward and reverse 
orientations separated by 6 nucleotides that comprise the loop of the RNA.  The suspension 
cell-based production process utilizes a lineage of HEK 293 cells adapted to a protein-free 
medium. VXA-A1.1 final drug product (DP) is an oral enteric-coated tablet formulation.  
Subjects will be dispensed 7 vaccine tablets (1.5 x 1010 IU/tablet) to administer a dose of 
1.05 x 1011 IU [1 x 1011 IU ±0.5 log]  
CONTROL 
PRODUCTS 
Active Comparator: 
•
Fluzone Quadravalent (Fluzone®) influenza vaccine (QIV) suspension for
intramuscular (IM) injection (2015-2016 formula, Lot # U1440AB)
o
The potency of Fluzone® is being continuously monitored by SRID assay to
ensure that the vaccine remains within specification during the dosing period
of the study.
o
Stability testing (time 0) was initiated prior to the labeled expiry date (June 30,
2016) of the Fluzone®   Lot # U1440AB
Placebo:  
•
Oral tablets similar in appearance and number to active oral vaccine tablets
•
0.9% Sodium Chloride for Injection, USP

VXA-CHAL-201 
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08 June 2017 (Amend. 3) 
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5 
CHALLENGE VIRUS 
STRAIN AND DOSE 
Wild-type Influenza virus (A/California/H1N1 2009) human challenge strain (BB-MF 15915 and 
BB-MF 15942; WCCT Global).  WCCT Global has submitted Letters of Authorization for FDA 
to refer to and incorporate by reference, any and all information contained in the two Master Files 
for the use of the influenza challenge strain product described in Protocol VXA-CHAL-201. 
RESCUE 
TREATMENT 
Rescue treatment with oseltamivir will be available to any subject who develops severe 
influenza illness post-challenge, as judged by the Investigator. Otherwise, challenged 
subjects will receive a 5-day course of therapy if symptomatic at discharge, based on 
Investigator discretion. 
STUDY OBJECTIVES 
Primary Objectives: 
•
Further establish the safety and tolerability of the VXA-A1.1 oral vaccine
•
Determine the clinical efficacy of VXA-A1.1 to protect against illness caused by
the homologous A strain influenza virus challenge 3 months following a single
immunization in comparison to placebo and QIV
Secondary Objectives: 
•
Determine the ability of VXA-A1.1 to modify disease severity compared to QIV
and placebo
•
Determine the correlation of immunogenicity parameters with clinical outcome
•
Determine the quantity and duration of influenza virus shedding by qRT-PCR
•
Evaluate the immunogenicity of VXA-A1.1:
•
Assess the ability of VXA-A1.1 to elicit serological and cellular immune
responses against the matched challenge strain in comparison to licensed
QIV
•
Assess the ability of VXA-A1.1 to elicit more broadly cross- reactive
serological immune responses in comparison to licensed QIV
Exploratory Objectives: 
•
Determine the resulting vaccine specific immune response by CyTOF (Mass flow
cytometry) and antibody repertoire sequence analysis, comparing oral VXA-A1.1
to the inactivated QIV vaccine for homing, memory, and activation of B and T
cells.
STUDY DESIGN, 
REGIMEN AND 
DOSING 
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 (+30 day window) 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 (Fluzone®), and/or 
placebo (double-dummy design).   
An independent Safety Monitoring Committee (SMC) will convene at regular intervals during 
the influenza challenge period, and also ad hoc as needed during the vaccination and challenge 
periods, to 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 
approximately 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: Fluzone®: Placebo).   

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08 June 2017 (Amend. 3) 
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STUDY DESIGN, 
REGIMEN AND 
DOSING (cont.) 
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 tablets [1x1011 IU±0.5 log] + placebo IM injection
(n=72 subjects) 
•
Arm 2:  Fluzone® IM injection + oral placebo tablets (n=72 subjects)
•
Arm 3: Placebo IM injection + oral placebo tablets (n=36 subjects)
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 (see Study 
Schedule section below as well as Schedule of Study Events, Table 1). 
Part B: Following confirmation of eligibility, subjects will be challenged with a wild-type 
influenza A H1 virus strain (A/H1N1 pdm09) 90 days (+30 day window) following 
vaccination (~25 subjects/ cohort). Blood samples will be collected to evaluate 
immunogenicity at pre-challenge. Subjects will remain in the isolation unit for at least 6, 
and up to 9 days post-challenge (see Study Schedule section below as well as Schedule of 
Study Events, Table 1). 
Following challenge, influenza symptoms will be systematically collected using the Flu-
PRO questionnaire, which will be completed by the subject once daily in the evening 
through 14 days post challenge. Additionally, signs of influenza will be assessed by the 
Investigator once daily via a targeted physical exam during the sequestration period.  
Blood samples, nasopharyngeal swab samples and tissue paper weights will also be 
collected (Table 1). Vital signs will be measured approximately every 4 hours, starting at 
the time of challenge administration.  After release from the isolation unit subjects will 
return to the site 30 days post-challenge for a final efficacy and routine safety (unsolicited 
AEs) follow-up visit.   
Part B will continue for purposes of collecting long term safety follow-up (SAEs and 
AESIs/NOCIs) via monthly phone contacts through 1 year post-vaccination  
(Day 365). 

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08 June 2017 (Amend. 3) 
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STUDY SCHEDULE 
The following study visits and telephone contacts will be conducted during the study (also 
see Tables 1a and 1b, Schedule of Study Events): 
Part A Visits (Vaccine-related): 
•
Pre-Screening Period (within 120 days prior to vaccination) [for purposes of
ascertaining subjects with low or undetectable pre-existing HAI antibodies (≤10) to
A/California/7/2009 (H1N1)-like virus]
•
Screening Period (within 45 days prior to vaccination)
•
Day 1 Visit (Baseline assessments; day of randomization and vaccination)
•
Day 3 Visit (Safety labs and cellular immunological sample collection)
•
Day 8 Visit (Cellular immunological sample collection)
•
Day 30 Visit (Serological sample collection)
•
Day 60 Visit (Safety checks)
•
Day 90 Visit (Serological and cellular immunological sample collection)
In Part A subjects will be followed via phone call on Days 2, 4 to 7, 15 and then every two 
weeks between site visits on Days 45 and 75 for safety.  
Part B Visits (Challenge-related):  
Starting at Day 90 post vaccination (Day of Challenge is Day B1) 
•
Day 90 (B1) (+30 day window; subjects challenged with influenza virus)
•
Days 89 – 95+ (B[-1] – B6+) (Subjects sequestered)
•
Day 120 (B30) (Post-Challenge; End of Active/Interventional Period)
•
Day 365 (End of Study Follow-up Period)
In Part B subjects will be sequestered one day prior to viral challenge at Day 89 (B[-1]),
with challenge at Day 90 (+30 days) at Day B1, and remain sequestered for 6 to 9 days.
They will return to the site 30 days following their challenge, for their final efficacy and
routine safety (unsolicited AEs) site visit.
Daily clinical assessments, Flu-PRO questionnaire by subjects (symptoms of influenza), 
targeted physical exam by physician (signs of influenza), blood collection for cellular 
immunological, nasopharyngeal swabs and tissue paper weight (nasal secretions) collection 
will be performed routinely during the sequestration period per the schedule of events in 
Table 1b.  Flu-PRO questionnaire will continue to be completed once daily by the subject 
from discharge to Day 14 post challenge. 
Blood samples for safety laboratory assessments (chemistry and hematology) will also be 
collected at Days B1, B3 and B6 post challenge, and more often if clinically indicated, per 
the discretion of the Investigator. 
Clinical assessments for safety and safety laboratory and cellular immunological blood 
sample collection will also be performed on the Day B30 post challenge clinic visit 
Subjects will also be contacted monthly between their Day B30 post-challenge visit and 
Day 365 for long-term safety follow-up (SAEs and AESIs/NOCIs). 

VXA-CHAL-201 
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08 June 2017 (Amend. 3) 
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INCLUSION 
CRITERIA 
1.
Male or female volunteers aged 18 – 49 years, inclusive
2.
Able to give written informed consent
3.
Low or undetectable pre-existing antibodies to the study vaccine as determined by an 
HAI titer of ≤10 against A/California/7/2009 (H1N1)-like viruses, measured within 120
days prior to vaccination 
4.
Healthy (no clinically significant health concerns), as determined by medical
history, physical examination, 12-lead ECG, and vital signs at screening
5.
Safety laboratory values within the following range criteria at screening:
a.
Normal range or < grade 1 elevation from normal (or decreased with NCS) for
ALP, ALT, AST and bilirubin;
b.
Normal range for neutrophils (neutropenia) or elevated with NCS;
c.
Normal range (or abnormality with NCS) for:
albumin, magnesium, total protein, hemoglobin, lymphocytes, white blood
cells, platelets; phosphorous, amylase, BUN, CPK, creatinine, eosinophils,
calcium, glucose, potassium and sodium;
d.
Negative laboratory value (or positive with NCS) for urine protein and blood
urine
6.
Body mass index between 17 and 35 at screening
7.
Comprehension of the study requirements with ability and willingness to complete
all assessments and comply with scheduled visits and contacts
8.
Female participants must have a negative pregnancy test at screening and baseline and
fulfill one of the following criteria:
a.
At least one year post-menopausal;
b.
Surgically sterile;
c.
Use of oral, implantable, transdermal or injectable contraceptives for 30 days
prior to immunization and until 30 days after challenge (Day B30);
•
A reliable form of contraception approved by the Investigator
(e.g. double barrier method, Depo-Provera, intrauterine device, Norplant,
oral contraceptives, contraceptive patches, abstinence)
EXCLUSION 
CRITERIA 
1.
Receipt of any influenza vaccine within two years prior to study vaccination or plans to
receive influenza vaccine during the active/interventional period of the study (i.e.,
through Day B30)
2.
Administration of any investigational vaccine or investigational adjuvanted vaccine
within 8 weeks preceding vaccination, or planned use of the above stated during the
study through the 12-month safety follow-up period
3.
Use of any investigational drug or device the greater of:  within 4 weeks preceding 
vaccination, or planned use of the above stated during the study through the study active
period (Day B30) OR within 5 half-lives of an investigational drug product
4.
Administration of any licensed vaccine within 30 days prior to vaccination or planned
use of the above stated during the active/interventional period of the study (i.e., through 
Day B30)
5.
Presence of significant uncontrolled medical or psychiatric illness (acute or chronic)
including institution of new medical/surgical treatment or significant dose alteration for
uncontrolled symptoms or drug toxicity within 3 months of screening and reconfirmed
at baseline
6.
Any one of the following ECG findings within 30 days prior to vaccination:
a.
QTc F (interval duration > 450 msec (male) or > 470 msec (female),
b.
QRS interval greater than 120 msec,

VXA-CHAL-201 
VXA-A1.1 Vaccine 
08 June 2017 (Amend. 3) 
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9 
EXCLUSION 
CRITERIA (cont.) 
c.
PR interval greater than 220 msec,
d.
Clinically significant ST-T wave changes or pathologic Q waves
7.
Positive serology for HIV-1 or HIV-2, or HBsAg or HCV antibodies
8.
Cancer, or treatment for cancer, within past 3 years (excluding basal cell carcinoma,
squamous cell carcinoma, and cervical cancer in situ)
9.
Presence of immunosuppression or medical condition possibly associated with impaired
immune responsiveness or increased risk of severe influenza illness, including diabetes
mellitus
10. Administration of any medications or treatments that may adversely affect the immune
system such as allergy injections, immune globulin, interferon, immunomodulators,
cytotoxic drugs or other drugs known to be associated with significant major organ
toxicity, or systemic/inhaled corticosteroids during 3 months prior to vaccination or
planned use of the above stated through 30 days post-challenge. Topical corticosteroids
allowed
11. Presence of household members who have received the Ad4 or Ad7 vaccines within
2 months prior to vaccination
12. Presence of household members who are neonates, pregnant women, or hematopoietic
stem cell transplant or solid organ transplant recipients or who are
immunocompromised including those who are HIV positive.
13. History of drug, alcohol or chemical abuse within 1 year prior to vaccination
14. Receipt of blood or blood products 6 months prior to vaccination or planned
administration during the follow-up study period
15. Donation of blood or blood products within 4 weeks prior to vaccination or
planned donation during the follow-up study period
16. Acute disease within 72 hours prior to vaccination defined as the presence of a
moderate or severe illness with or without fever (as determined by the Investigator
through medical history and physical examination) or any acute respiratory or
gastrointestinal illness even with mild symptoms occurring within 7 days of dosing the
vaccine and within 7 days of entering the challenge phase
17. Presence of a fever ≥ 38ºC measured orally at baseline
18. Stool sample with occult blood at screening 
19. Positive urine drug screen for drugs of abuse at screening or baseline
20. Positive breath or urine alcohol test at screening or baseline
21. Consistent/habitual smoking (> 2 cigarettes/week) within 2 months prior to
vaccination
22. History of serious reactions to any vaccination such as anaphylaxis, respiratory 
problems, Guillain-Barre syndrome, hives or abdominal pain
23. History of documented egg allergy
24. History of a hypersensitivity or allergic reaction to any component of the investigational
vaccine or placebo, including but not limited to fish gelatin
25. History of a hypersensitivity or allergic reaction to any component of the licensed QIV
comparator vaccine (Fluzone®), including but not limited to eggs
26. Diagnosed bleeding disorder or significant bruising or bleeding difficulties that could
make blood draws problematic or those with poor venous access that will make
venipuncture difficult
27. History of irritable bowel disease or inflammatory digestive or gastrointestinal
condition that could affect the distribution / safety evaluation of an orally administered
vaccine targeting the mucosa of the small intestine.
Such conditions may include but are not limited to:
a.
Esophageal Motility Disorder

VXA-CHAL-201 
VXA-A1.1 Vaccine 
08 June 2017 (Amend. 3) 
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EXCLUSION 
CRITERIA (cont.) 
b.
Malignancy
c.
Malabsorption
d.
Pancreaticobiliary disorders
e.
Irritable bowel syndrome
f.
Celiac Disease
g.
Inflammatory Bowel Disease
h.
Surgical Resection with the exception of appendectomy or a minor resection 
that is deemed acceptable by investigator and sponsor
i.
GERD
j.
Hiatal Hernia
k.
Peptic Ulcer
(History of cholecystectomy is not exclusionary)
28. Any condition that resulted in the absence or removal of the spleen
29. History of any form of angioedema
30. Use of concomitant medications such as those listed below unless the subject can safely 
discontinue these medications for the rest of the study; none of these can be taken 
within 30 days of vaccination:
a.
Proton pump inhibitors
b.
Over-the-counter probiotics
c.
H2-blockers
d.
Anti-seizure medications
e.
Pain relief medications (chronic use)
f.
Cardiovascular drugs
g.
Imidazoles, Triazoles, and Thiozole antifungals
h.
Antidiarrheals
i.
Antibiotics
i.
Use of a brief (≤ 10 days) course of oral or topical antibiotic for
minor URI, UTI, dental work, or skin infection allowed within the
screening period, but must be completed 7 days prior to vaccination
j.
Influenza antiviral medications (from screening to viral challenge)
31. The use of stable doses of prior and concomitant medications for the below
indications is allowed:
a.
Dyslipidemia:  No new agents for treatment or changes in dose of agents
already in use within 3 months prior to screening (includes niacin
obtained without prescription)
b.
Thyroid medications: Must be on a stable dose of medication
(eg, levothyroxine) for at least 3 months prior to screening
32. Any condition that, in the opinion of the Investigator, might interfere with ability to
assess the primary study objectives
33. Adulthood history of seasonal hay fever or a seasonal allergic rhinitis or perennial
allergic rhinitis or chronic or nasal or sinus condition such as chronic sinusitis,
abnormal nasal structure including septal deviation and nasal polyps unless the allergic
rhinitis has been asymptomatic for the last 5 years.
34. Asthma, bronchiectasis or chronic obstructive pulmonary disease
35. Any known allergy or intolerance to oseltamivir
SAFETY, 
IMMUNOGENICITY, 
AND EFFICACY 
ASSESSMENTS 
Safety: 
PART A: Post-Vaccination (Day 1 to Day 90) 
Safety and tolerability will be evaluated by:  
•
Solicited symptoms listed below through Day 8:
o
Gastrointestinal reactions (nausea, vomiting, diarrhea and abdominal pain) for

VXA-CHAL-201 
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08 June 2017 (Amend. 3) 
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SAFETY, 
IMMUNOGENICITY, 
AND EFFICACY 
ASSESSMENTS (cont.) 
oral component 
o
Injection site reactions (localized pain, tenderness, erythema and induration)
for IM component,
o
Symptoms/signs of systemic reactogenicity (malaise/fatigue, myalgia,
anorexia, fever and headache)
•
Unsolicited AEs will be recorded through 120 days post-immunization
(90 days in Part A and 30 days post challenge in Part B)
•
SAEs and AESIs/NOCIs will be recorded through Day 365
•
Physical exams, routine urinalysis, complete blood counts and serum chemistries will
be collected pre-dose at Screening and Baseline and at Study Days 3, 8, 30, 90 (pre-
challenge)
•
Vital signs will be recorded at all study visits
•
Female participants will have serum/urine pregnancy tests at screening, baseline, Day
30 and pre-challenge (Day 89 or Day 90).
PART B: Challenge Phase: 
Safety: 
•
Unsolicited AEs through 30 days post-challenge (Day B30 Visit)
•
Pre-challenge and daily throughout the sequestration period post-challenge:
o
Pulmonary function using a spirometer to assess forced vital capacity (FVC),
(forced expiratory volume in one second) FEV1, peak expiratory flow (PEF),
and the FEV1/FVC ratio;
o
Vital signs (blood pressure, heart rate (HR), respiratory rate, oral body
temperature, and oxygen saturation (pulse ox) approximately every 4 hours,
starting at the time of challenge administration)
o
12-lead electrocardiograms (ECGs)
o
Assessment of safety laboratory panels (chemistry, hematology, and
urinalysis) on Days B1, B3 and B6. Additional time points may be collected
if clinically indicated per the discretion of the Investigator.
•
Follow-up clinic evaluations on 30 days post-challenge at Day B30 Visit
Immunogenicity/Efficacy:
Post-vaccination (See Table 1, Part A)
Cellular and/or humoral immune function assays from blood samples obtained at 
baseline (pre-dose) and at protocol-specified Study Days 8, 30 and 90 (pre-challenge), 
depending on the assay. In addition, a final evaluation for immune status may be 
performed 30 days post-challenge. 
HA antibody response will be determined using HAI assay, a microneutralizing (MN) 
assay and by ASC assay. Anti-Adenovirus 5 immune responses will be measured at 
baseline (pre-immunization) and on Day 30.  
T cell responses will be measured by an HA-specific interferon-γ (IFN-γ) / granzyme B 
(GrB) dual ELISpot assay  
Challenge Phase (See Table 1, Part B) 
Solicitation of acute influenza symptoms post-challenge once each evening by the 
subject (Flu-PRO) through to Day 14 post-challenge, and signs of influenza once daily 
by the investigator during the sequestration period. 
Daily Pulmonary function using a spirometer to assess forced vital capacity (FVC), 
(forced expiratory volume in one second) FEV1, peak expiratory flow (PEF), and the 
FEV1/FVC ratio 
Nasopharyngeal swabs for multiplex molecular testing for respiratory viruses by 
Biofire FilmArray System or Luminex; influenza virus shedding 2 times daily during 
the sequestration period by quantitative RT-PCR 

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Nasopharyngeal swabs to determine absence of viral shedding at baseline and 
prior to discharge: 
o A rapid influenza test will be used to access for the absence of viral shedding
starting on Day 5 post challenge; once the rapid influenza test becomes
negative on or after day 5, the subject’s negative shedding status will be
confirmed on that same day and the subsequent day using Biofire or Luminex
to document negative PCR for 2 consecutive days. Oseltamivir therapy (5
days) will be begun at discharge in subjects that are symptomatic at discharge,
per the discretion of the investigator.
Tissue paper weights (nasal secretions) will be determined once each day, in the 
morning during the sequestration period 
HALTING RULES 
Halting Rules for study Part B are listed below.  For each individual cohort, if any of these 
conditions are met during the sequestration period post viral challenge, no new enrollment 
or further challenge virus administration in subsequent cohorts will be initiated pending a 
full SMC safety review.   
1.
One or more subjects has a body temperature ≥103°F (39.4°C) that is not
responsive to acetaminophen;
2.
One or more subjects has a reduction of forced expiratory volume in one
second (FEV1) below 70% of the baseline value, difficulty breathing,
oxygen saturation <90% while awake, or other evidence of lower
respiratory tract involvement if deemed clinically significant by the
investigator;
3.
One or more subjects experience a treatment-related SAE or grade 4 clinical AE,
or two or more subjects experience the same treatment-related grade 3 clinical
AE or treatment-related grade ≥3 laboratory abnormality.
The SMC will provide study oversight throughout the duration of the trial interventional 
and safety follow-up period (Day 0 through Day 365 post-vaccination). The IRB and 
CBER will be notified if the study is halted for safety concerns. 

VXA-CHAL-201 
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STUDY ENDPOINTS 
Efficacy: 
Primary: 
The primary efficacy endpoint is the occurrence of illness (attack rate) caused by the 
homologous A strain influenza virus challenge at 3 months.   
Attack rate is defined as subjects experiencing at least one day with: 
1) Two symptoms present of at least “A little bit”, “1 time” or “Rarely” or one symptom
present of at least “Somewhat”, “2 times” or “Sometimes” among the acute influenza
symptoms on the Flu-PRO (Appendix 2)
and 
2) laboratory-confirmed infection (≥2 positive quantitative RT-PCR results while
sequestered)
Comparisons will be performed in: 
1) all challenged subjects in each respective vaccine group; and then
2) infected subjects (as defined by ≥2 positive quantitative RT-PCR results while
sequestered) in each vaccine group
Secondary: 
Flu-PRO symptom severity score (Appendix 2) 
Number of subjects with detectable shedding by qRT-PCR 
Virus shedding AUC by qRT-PCR  
Duration of shedding as detected by qRT-PCR 
Tissue paper weights 
Number of symptoms per Flu-PRO (Appendix 2) 
Number of signs per physician assessment (Appendix 3) 
Correlations between individual immunogenicity parameters (see below) and clinical 
efficacy 
Safety – Number (%) of subjects reported solicited (through Day 8), unsolicited adverse 
events (through Day 120), and SAEs and AESIs through Day 365; findings of clinical 

VXA-CHAL-201 
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14 
laboratory tests; findings of vital signs; and findings of physical examination and 
pulmonary function compared to placebo and QIV. 
Secondary Immunological: 
IgA and/or IgG ASC at Day 8, T cell (IFN-γ and GrB) responses at Day 8 against matched 
strain compared to licensed QIV and placebo 
Geometric mean titers of HAI, MN against matched strain compared to licensed QIV and 
placebo at Day 30 
Geometric mean titers of HAI, MN against mismatched strains when compared to licensed 
QIV at Day 30 
Geometric mean titers of HAI against matched strain compared to licensed QIV and 
placebo at Day 90 (pre-challenge) for all challenged subjects 
Exploratory: 
Determine the resulting vaccine specific immune response by CyTOF (Mass flow 
cytometry) and antibody repertoire sequence analysis, comparing oral VXA-A1.1 to the 
inactivated QIV vaccine for homing, memory, and activation of B and T cells. 
STATISTICAL 
CONSIDERATIONS 
This is a proof-of-concept study to determine whether VXA-A1.1 may enhance efficacy 
and/or immunogenicity when compared with licensed QIV. All analyses will be descriptive 
in nature, in which results for various endpoints described above will be compared among 
VXA-A1.1, QIV and placebo groups. No formal evaluation of sample size was performed 
with respect to these endpoints. Group sizes of 60, 60 and 30 are generally larger than those 
in previous influenza challenge studies in which subjects have received prior vaccination, 
and therefore should be large enough to detect any signals suggestive of improved efficacy 
or immunogenicity. No statistical adjustments will be made to account for multiplicity. 
In doing the analysis, any subjects who had elevated HAI titers greater than 1:10 on the pre 
vaccination (baseline) blood sample should be excluded from statistical analysis and should 
be excluded from the challenge phase analysis if they are enrolled. 

VXA-CHAL-201 
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08 June 2017 (Amend. 3) 
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Table 1 
Schedule of Events 
Part A (Vaccination Period) 
Assessments 
Pre-
Screen1 
(Day -120 
to Screen) 
Screen 
(Day -45 
to Day -1)
Baseline2 
(Day -2 to 
Day 1 Visit) 
Day 3 
Visit 
Days 2, 4-7 
and 
Day 15* 
Contact 
Day 8 
(Week 1) 
Visit 
Day 30 
Visit 
Day 60 
Visit 
Day 45 and 
Day 75 
Contact 
Day 90 Visit 
(Non-
Challenge 
Subject) 
Early Term 
(Day 0 – 
30) 
Early Term 
(Day 31 –90 
pre-
challenge) 
Windows 
N/A 
N/A 
N/A 
+1 day
±2 days* 
None 
±2 days 
±1 
week 
±1 week 
+30 days
N/A 
N/A 
Serum for Prescreening HAI Titer 
X1 
Informed Consent 
X 
X 
Demographics 
X 
Review Eligibility Criteria 
X 
Medical History 
X 
Physical Examination 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECG
X 
X 
Spirometry 
X 
Blood Sample – safety labs (fasting) 
X 
X 2 
X 
X 
X 
X 
X 
Blood Sample – HIV ELISA, HCV 
ELISA, HBV sAg 
X 
Urinalysis 
X 
X 2 
X 
X 
X 
X 
X 
Urine Drug Screen 
X 
X 
X 
Breath or Urine Alcohol Test 
X 
X 
X 
Serum/Urine Pregnancy Test 
X 
X 
X 
X 
X 
Immunogenicity: Serum Assays – 
anti-Ad5 3, HAI, MN 
X 2 
X 
X 
X 
X 
Immunogenicity: PBMC Assays – 
ASCs, CyTOF, Ab Sequencing) 
X 2 
X 
X 
X 
Immunogenicity: Fixed Whole Blood
– CyTOF, cytocines) [heparinized
tubes]
X 2 
X 
X 
X 
X 
X 
Gene Expression: RNA (PAXgene 
Blood RNA® Tubes) 
X 2 
X 
X 
Stool Sample for Occult Blood 
X 
Vaccination 
X 

VXA-CHAL-201 
VXA-A1.1 Vaccine 
08 June 2017 (Amend. 3) 
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Assessments 
Pre-
Screen1 
(Day -120 
to Screen) 
Screen 
(Day -45 
to Day -1)
Baseline2 
(Day -2 to 
Day 1 Visit) 
Day 3 
Visit 
Days 2, 4-7 
and 
Day 15* 
Contact 
Day 8 
(Week 1) 
Visit 
Day 30 
Visit 
Day 60 
Visit 
Day 45 and 
Day 75 
Contact 
Day 90 Visit 
(Non-
Challenge 
Subject) 
Early Term 
(Day 0 – 
30) 
Early Term 
(Day 31 –90 
pre-
challenge) 
Windows 
N/A 
N/A 
N/A 
+1 day
±2 days* 
None 
±2 days 
±1 
week 
±1 week 
+30 days
N/A 
N/A 
Dispense Diary Card(s) 4 
X 
X 
X 
X 
Collect Diary Card(s) 
X 
X 
X 
X 
X 
X 
Review of Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess for AEs5, SAEs and AESIs/ 
NOCIs & Review Diary Cards 
X 8 
X 8 
X 8 
X 8 
X 
X 
X 
X 
X 
X 
1 Pre-screening for low or undetectable pre-existing antibodies to the study vaccine as determined by an HAI titer of ≤10 against A/California/7/2009 (H1N1)-like viruses 
2 Baseline blood samples may be drawn at up to two days (Day -2) of vaccination. Baseline safety labs do not need to be repeated if screening safety labs collected within two days of 
vaccination. 
3 Anti-Ad5 assay is not performed on serum collected at Day 90 
4 (1) Symptom Diary Card: solicited symptoms of reactogenicity from Day 1 – Day 8 Visit; (2) General Diary Card: clinical symptoms/events and con meds from Day 8 – Day 120 (B30) 
Visit;  (3) AESIs/NOCIs Diary Card: AESIs/NOCIs from Day 120 (B30) Visit – Day 365 Contact 
5 Monitor AEs for acute symptoms of conjunctivitis, URI, loose stools/diarrhea within 7 days post-vaccination to evaluate for Ad5 infection. If reported, collect throat and rectal swabs and 
forward to test lab. 

Protocol VXA-CHAL-201 
VXA-A1.1Vaccine 
08 June 2017 (Amend. 3) 
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Part B (In-Patient Challenge Period) 
Study Visits/Quarantine 
Assessment Period (Days) 
Study Day (Part B) 
B(-1) 
(Day 89) 
(B1) 
(Day 90) 
(B2) 
(B3) 
(B4) 
(B5)1 
(B6)1 
(B7)1 
(B8)1 
(B9)1 
Windows 
-2 days
+ 30
N/A 
N/A 
N/A 
N/A 
N/A 
N/A 
N/A 
N/A 
Out Patient Period 
Quarantine Period 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Informed Consent 2 
X5 
X5 
Review Eligibility Criteria 
X5 
X5 
Vital Signs 3 
X5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG and Spirometry 4
X5 
X5 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Examination 
X5 
X5 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity: Serum Assays – anti-Ad5 6, 
HAI, MN 
X5 
X5 
X 
Immunogenicity: PBMC Assays – ASCs, CyTOF, 
Ab Sequencing) 
X5 
X5 
X 
X 
Immunogenicity: Fixed Whole Blood – CyTOF, 
cytokines) [heparinized tubes] 
X5 
X5 
X 
X 
X 
X 
X 
Gene Expression: RNA (PAXgene Blood RNA® 
Tubes) 
X5 
X5 
X 
Serum/urine Pregnancy Test 
X5 
X5 
Serum/urine Drug and Breath/urine Alcohol Tests 
X5 
X5 
Blood Sample – safety labs (fasting) 
X5 
X5 
X 
X 
Urinalysis 
X5 
X5 
X 
X 
Viral Challenge 
X7 
Influenza Symptom and Signs Scoring 8  
X5 
X5 
X 
X 
X 
X 
X 
X 
X 
X 
Nasopharyngeal Swabs for Viral 
Shedding/efficacy (qRT-PCR) 9 
X5 
X5 
X 
X 
X 
X 
X 
X 
X 
X 
Nasopharyngeal Swabs (rapid influenza test & 
Biofire/Luminex) 10 
X5 
X5 
X 
X 
X 
X 
X 

Protocol VXA-CHAL-201 
VXA-A1.1Vaccine 
08 June 2017 (Amend. 3) 
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Study Visits/Quarantine 
Assessment Period (Days) 
Study Day (Part B) 
B(-1) 
(Day 89) 
(B1) 
(Day 90) 
(B2) 
(B3) 
(B4) 
(B5)1 
(B6)1 
(B7)1 
(B8)1 
(B9)1 
Windows 
-2 days
+ 30
N/A 
N/A 
N/A 
N/A 
N/A 
N/A 
N/A 
N/A 
Tissue Paper Weights (nasal secretions) 
X11 
X 
X 
X 
X 
X 
X 
X 
X 
Oseltamivir Administration 12 
X12 
Review Concomitant Medications 
X 
X11 
X 
X 
X 
X 
X 
X 
X 
X 
Assess for Adverse Events (including  SAEs and 
AESIs/NOCIs) 
X 
X11 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense  (at discharge) /Collect General 
Symptom Diary Card 
X11 
X 
X 
X 
Query for SAEs and AESIs. Review 
AESIs/NOCIs Diary Card 13 
1 Subjects will have rapid influenza test daily starting on Day B5. If rapid influenza is test negative subjects will have confirmatory test (Biofire or Luminex) performed the same day and the 
subsequent day.  Subjects will be discharged based on the Biofire/Luminex test results, their influenza signs and symptoms and any other available data at the discretion of the Investigator. 
Assessments will only be made once unless the subject is not fit to leave the unit. If subjects are not discharged on Day B6, the same assessments will be performed on Days 7 through 9, 
except immunological testing. Subjects who withdraw consent prior to absence of viral shedding will be requested to remain in quarantine but will only undergo assessments to determine 
absence of viral symptomology and shedding before discharge.   
2 
In addition to the main Informed Consent Form (ICF), subjects will confirm consent prior to challenge in Part B 
3 Vital signs include blood pressure, heart and respiratory rate and body temperature. Blood pressure and heart rate will be measured in seated position after 5 min rest. Body temperature will b
measured orally. 
On Day B1, the morning vital signs measurement will be performed pre-challenge. From Day B1 to the day of discharge, vital signs will be performed approximately every 4 hours, starting 
 at the time of challenge administration.   
4 ECG and spirometry will be measured once daily in supine and seated position, respectively, after 5 min of rest. 
5 
Pre-challenge assessment.  May be completed at Day B-1 or Day B1 pre-challenge.
6 Anti-Ad5 assay is not performed on serum collected at Day 90 
7 Administration of challenge virus will be in the morning. 
8 Solicitation of acute influenza symptoms (Flu-PRO) will be completed by the subject in the morning prior to challenge and then every evening (after 3pm) and signs will be assessed by the 
investigator/study staff daily during the sequestration period. Subjects will continue to complete the Flu-PRO once daily following discharge to Day 14 post-challenge. 
9 Nasopharyngeal swabs for viral shedding (qRT-PCR) will be collected twice daily approximately 12 hours apart from Day B1 to day of discharge. Swabs should be collected from 
alternating nostrils (left or right) at each collection time point. The initial swab at Day B1 will be collected pre-challenge. 
10    A second nasopharyngeal swab will be collected for testing by Biofire/Luminex at baseline visit.  Subsequent testing by rapid influenza test starting at Day B5 with confirmation of 
negative results by Biofire/Luminex test starting at Day B6. Data will be reviewed before discharging subject from unit; subjects with 2 consecutive negative values by Biofire/Luminex 
test may be discharged starting at Day B6. 
11    Pre-challenge 
12 Oseltamivir (5-day course) will be administered to symptomatic subjects starting on day of discharge per the discretion of the investigator. 
13    AESIs/NOCIs Diary Card will be dispensed at the Day B30 Visit (end of active period/last efficacy visit) to assist subjects in recording symptoms of AESIs/NOCIs through Day 365.  Prior 
to Day B30. AESIs/NOCIs will be collected from Part A, Day 1 (vaccination) to Part B, Day B30 via site visits and phone contacts. 

Protocol VXA-CHAL-201 
VXA-A1.1Vaccine 
08 June 2017 (Amend. 3) 
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Follow-up Period 
Study Visits/Quarantine 
Assessment Period (Days) 
Study Day (Part B) 
Day B30 
(D120)/ ET 
Monthly 
Contact 
(Thru Day 365) 
Early Term 
(Day B2-B9) 
Early Term 
(Discharge–B30) 
Early Term (B30 – 
End of Safety 
Follow-up) 
Windows 
±2 days 
±1 week 
Out Patient Period 
X 
X 
Vital Signs 1 
X 
12-lead ECG and Spirometry 2
X 
Physical Examination 
X 
Immunogenicity: Serum Assays – anti-Ad5, HAI, MN 
X 
X 
X 
Immunogenicity: PBMC Assays – ASCs, CyTOF, Ab 
Sequencing) 
X 
Serum/urine Pregnancy Test 
X 
X 
X 
Blood Sample – safety labs (fasting) 
X 
X 
X 
Urinalysis 
X 
X 
X 
Oseltamivir Administration 3 
X 3 
Review Concomitant Medications 
X 
 X 
Assess for Adverse Events (including  SAEs and AESIs/NOCIs) 
X 
X 
X 
Dispense  (at discharge) /Collect General Symptom Diary Card 
X 
 X 
X 
Query for SAEs and AESIs. Review AESIs/NOCIs Diary Card 4 
X 
X 
1   Vital signs include blood pressure, heart and respiratory rate and body temperature. Blood pressure and heart rate will be measured in seated
position after 5 min rest. Body temperature will be measured orally
2   ECG and spirometry will be measured in supine and seated position, respectively, after 5 min of rest 
3  Oseltamivir (5-day course) will be administered to symptomatic subjects starting on day of discharge or termination per the discretion of the investigator. 
4  AESIs/NOCIs Diary Card will be dispensed at the Day B30 Visit (end of active period/last efficacy visit) to assist subjects in recording
symptoms of AESIs/NOCIs through Day 365.  Prior to Day B30. AESIs/NOCIs will be collected from Part A, Day 1 (vaccination) to Part B, 
Day B30 via site visits and phone contacts