A Phase 1b, Open-label, Boost-optimization Study of an Adenoviral- Vector Based Oral Norovirus Vaccine (VXA-G1.1-NN) Expressing GI.1 VP1 Administered Orally to Healthy Adult Volunteers
Phase: PHASE1
Conditions: Norovirus Infections
Sponsor: Vaxart

 
CLINICAL STUDY PROTOCOL 
TITLE PAGE 
 
Protocol Title: 
A Phase 1b, Open-Label, Boost-Optimization Study of an Adenoviral- 
vector Based Oral Norovirus Vaccine (VXA-G1.1-NN) Expressing 
GI.1 VP1 Administered Orally to Healthy Adult Volunteers  
Protocol Number: 
VXA-NVV-105 
Product Name: 
Norovirus GI.1 Norwalk VP1 Vaccine, Oral E1-/E3-Deleted 
Replication Defective Recombinant Adenovirus 5 with double-stranded 
RNA Adjuvant (VXA-G1.1-NN) 
Indication: 
Prevention of noroviral gastroenteritis caused by norovirus GI.1 
Study Phase 
Phase 1b 
Sponsor Name and 
Vaxart Biosciences, Inc. 
Address 
170 Harbor Way, Suite 300 
South San Francisco, CA 94080 
U.S. IND Number 
IND: 16796 
Sponsor Contact 
Shaily J. Garg, PMP 
SVP, Clinical Development and Project Management 
Phone: 650-521-4496 
Email: sgarg@vaxart.com 
Medical Monitor 
Dave Liebowitz, MD, PhD 
Phone: +1 (408) 340-8605 
Email: dliebowitz@vaxart.com 
Version and 
Approval Date                Amendment 1; August 25, 2021 
 
Previous version           Original; March 31, 2021 
 
Confidentiality Statement 
This document is confidential and is to be distributed for review only to investigators, potential investigators, 
consultants, study staff, and applicable independent Ethics Committees and/or Institutional Review Boards. 
The contents of this document shall not be disclosed to others without written authorization from Vaxart (or 
authorized designees) unless it is necessary to obtain informed consent from potential study participants. 

VAXART 
Protocol Number: VXA-NVV-105 
 
Amendment 1,  August 25 2021 
 
Page 2 of 62 
 
 
SIGNATURE PAGE/STATEMENT OF COMPLIANCE 
 
 
Title: 
A Phase 1b, open-label, boost-optimization study of an adenoviral- 
vector based oral norovirus vaccine (VXA-G1.1-NN) expressing 
GI.1 VP1 administered orally to healthy adult volunteers 
 
Protocol Number: 
VXA-NVV-105 (Amendment 1) 
 
 
 
Vaxart, Inc.:   
 
Date  
 
 
 
 
The study will be conducted in accordance with the International Council for Harmonisation 
(ICH) E6 and the Code of Federal Regulations on the Protection of Human Subjects (45 CFR 
Part 46). Except where necessary to eliminate an immediate hazard(s) to the study participants, 
the Principal Investigator will assure that no deviation from, or changes to the protocol will take 
place without prior agreement from the Sponsor and documented approval from the Institutional 
Review Board (IRB) and/or Independent Ethics Committee (IEC). All personnel involved in the 
conduct of this study have completed Human Subjects Protection Training. 
 
 
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments. 
 
 
 
 
Principal Investigator: 
Name: 
  
 
Signature 
  
 
  
 
Date 
(Print) 
Site & Address: 
  
 
 
 
 
 
 
 
 
 
 

VAXART 
Protocol Number: VXA-NVV-105 
 
Amendment 1,  August 25 2021 
 
Page 3 of 62 
 
TABLE OF CONTENTS 
TITLE PAGE ............................................................................................................................ 1 
SIGNATURE PAGE/STATEMENT OF COMPLIANCE ................................................... 2 
TABLE OF CONTENTS ......................................................................................................... 3 
LIST OF TABLES .......................................................................................................................................................... 5 
1. 
PROTOCOL SUMMARY ........................................................................................... 6 
1.1. 
SYNOPSIS ....................................................................................................................................................... 6 
1.2. 
SCHEDULE OF ACTIVITIES ......................................................................................................................10 
2. 
INTRODUCTION. ...................................................................................................... 12 
2.1. 
STUDY RATIONALE ..................................................................................................................................12 
2.2. 
BACKGROUND ............................................................................................................................................13 
2.3. 
BENEFIT/RISK ASSESSMENT .................................................................................................................13 
2.3.1. Benefit Assessment ................................................................................................................... 14 
2.3.2. Overall Benefit/Risk Conclusion .............................................................................................. 14 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 15 
4. 
OVERALL STUDY DESIGN .................................................................................... 16 
4.1. 
SCIENTIFIC RATIONAL FOR STUDY DESIGN .....................................................................................17 
4.2. 
JUSTIFICATION FOR VARYING DOSE SCHEDULES ............................................................. 17 
4.3. 
STUDY DURATION ....................................................................................................................................17 
4.4. 
END OF STUDY DEFINITIONS .................................................................................................................17 
4.5. 
4.5.  SAFETY AND FINAL DATABASE Lock ....................................................................... 17 
5. 
ELIGIBILITY CRITERIA ........................................................................................ 18 
5.1. 
INCLUSION CRITERIA ...............................................................................................................................18 
5.2. 
EXCLUSION CRITERIA ..............................................................................................................................19 
5.3. 
SCREEN FAILURES ....................................................................................................................................21 
6. 
STUDY DRUG, CONCOMITANT THERAPY AND LIFE-STYLE 
CONSIDERATIONS .................................................................................................. 22 
6.1. 
STUDY DRUG ADMINISTRATION ..........................................................................................................22 
6.2. 
COMPLIANCE OF STUDY DRUG .............................................................................................................23 
6.2.1. Dose Adjustments/Modifications/Delays. ................................................................................. 23 
6.3. 
HANDLING AND ACCOUNTABILITY .....................................................................................................23 
6.4. 
TREATMENT OF OVERDOSE ...................................................................................................................25 
6.5. 
CONCOMITANT THERAPY .......................................................................................................................25 
6.5.1. Prohibited Concomitant Medication ......................................................................................... 25 
6.6. 
INTERVENTION AFTER THE END OF THE STUDY .............................................................................25 
7. 
DISCONTINUATION OF STUDY DRUG AND PARTICIPANT 
WITHDRAWAL FROM STUDY ............................................................................. 26 
7.1. 
DISCONTINUATION OF STUDY DRUG..................................................................................................26 
7.2. 
Early Termination Visit (Active or Follow-Up Period)………………………….……………27 
7.3. 
PARTICIPANT WITHDRAWAL FROM THE STUDY .............................................................................27 

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7.4. 
LOST TO FOLLOW-UP ...............................................................................................................................27 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 28 
8.1. 
IMMUNOGENICITY ASSESSMENTS .......................................................................................................28 
8.2. 
SAFETY ASSESSMENTS ............................................................................................................................29 
8.2.1. Physical Examination ................................................................................................................ 29 
8.3.       VITAL SIGNS .................................................................................................................. 29 
8.3.1      Clinical Safety Laboratory Assessments .................................................................................. 29 
8.4.         ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS......................................................29 
8.4.1.    Time Period and Frequency for Collecting AE, SAE and Other Reportable 
 
Safety Event Information .......................................................................................................... 30 
8.4.2     Method of Detecting AEs and SAEs ......................................................................................... 32 
8.4.3.    Follow-up of AEs and SAEs ..................................................................................................... 32 
8.4.4.    Regulatory Reporting Requirements for SAEs ......................................................................... 32 
8.4.5.    Death Events ............................................................................................................................. 32 
8.4.6.    Pregnancy .................................................................................................................................. 32 
9. 
STATISTICAL CONSIDERATIONS ...................................................................... 33 
9.1. 
SAMPLE SIZE DETERMINATION ............................................................................................................33 
9.2. 
STATISTICAL ANALYSES ........................................................................................................................33 
9.2.1. Safety Analysis ......................................................................................................................... 34 
9.2.2. Immunogenicity Analysis ......................................................................................................... 35 
9.3. 
SAFETY OVERSIGHT .................................................................................................................................35 
9.3.1. Internal Sponsor Review ........................................................................................................... 35 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS .................................................................................................. 37 
10.1. APPENDIX 1: REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS ........37 
10.1.1. Regulatory and Ethical Considerations ..................................................................................... 37 
10.1.2. Financial Disclosure .................................................................................................................. 37 
10.1.3. Informed Consent Process ......................................................................................................... 38 
10.1.4. Exclusion of Women, Minorities, and Children (Special Populations) .................................... 38 
10.1.5. Data Protection .......................................................................................................................... 38 
10.1.6. Dissemination of Clinical Study Data ....................................................................................... 39 
10.1.7. Data Quality Assurance............................................................................................................. 39 
10.1.8. Source Documents .................................................................................................................... 39 
10.1.9. Publication Policy ..................................................................................................................... 40 
10.2. APPENDIX 2: SAFETY CLINICAL LABORATORY TESTS ................................................................41 
10.3. APPENDIX 3: ADVERSE EVENTS: DEFINITIONS AND PROCEDURES FOR RECORDING, 
 
EVALUATING, FOLLOW-UP, AND REPORTING .................................................................................42 
10.4. APPENDIX 4: CONTRACEPTIVE GUIDANCE AND COLLECTION OF PREGNANCY 
INFORMATION  ........................................................................................................................................... 50 

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10.4.1. Definitions ................................................................................................................................. 50 
10.4.2. Contraception Guidance ............................................................................................................ 50 
10.4.3. Collection of Pregnancy Information ........................................................................................ 50 
10.5. APPENDIX 5: ADVERSE EVENTS OF SPECIAL INTEREST (AESIS) .................................... 51 
10.6. APPENDIX 6: ABBREVIATIONS .............................................................................................................53 
11. 
REFERENCES ............................................................................................................ 55 
 
List of Tables 
 
Table 1 
Treatment Arm, Doses and Sample Size ................................................................. 9 
Table 2 
Schedule of Activities ............................................................................................ 10 
Table 3 
Risk Assessment .................................................................................................... 14 
Table 4 
VXA-G1.1-NN Study Drug ................................................................................... 22 
Table 5 
Adverse Event Reporting Timelines to the Sponsor .............................................. 31 
Table 6 
Protocol-Required Safety Laboratory Assessments .............................................. 41 
Table 7 
Definition of AE (Unsolicited and Solicited) ........................................................ 42 
Table 8 
Events Meeting Definition of AE .......................................................................... 42 
Table 9 
Definition of SAE .................................................................................................. 43 
Table 10     Definition of AESI and NOCI……………………………………………………43 
Table 11 
Recording of AE and/or SAE ................................................................................ 44 
Table 12 
Grading the Severity of AEs .................................................................................. 45 
Table 13 
Grading of Solicited Symptoms of Reactogenicity ............................................... 46 
Table 14 
Grading of Laboratory Abnormalities (Serum Chemistry) ................................... 47 
Table 15 
Grading of Laboratory Abnormalities (Hematology) ............................................ 47 
Table 16 
Grading of Laboratory Abnormalities (Urinalysis) ............................................... 48 
Table 17 
Assessment of Causality ........................................................................................ 48 
Table 18 
Reporting of SAEs ................................................................................................. 49 

VAXART 
Protocol Number: VXA-NVV-105 
 
Amendment 1,  August 25 2021 
 
Page 6 of 62 
 
1. 
PROTOCOL SUMMARY 
1.1 Synopsis 
Protocol Title 
A Phase 1b, open-label, boost-optimization study of an adenoviral- vector based oral norovirus 
vaccine (VXA-G1.1-NN) expressing GI.1 VP1 administered orally to healthy adult volunteers. 
 
Study Rationale and Hypothesis 
VXA-G1.1-NN is an E1/E3-deleted, replication-incompetent, adenovirus 5 (Ad5) vaccine 
vectors designed for use as an oral vaccine for the prevention of noroviral gastroenteritis caused 
by norovirus genogroups GI.1. The monovalent vaccine vector encodes the full-length of viral 
protein 1 (VP1) gene of Norwalk virus (Norovirus GI.1). The adjuvant consists of a double- 
stranded RNA Toll-like receptor 3 (TLR3) agonist which enhances immune induction to 
expressed antigen in the gut mucosa. 
Noroviruses are a genetically diverse group of small, non-enveloped, single-stranded positive 
sense RNA viruses belonging to the Caliciviridae family (Bresee, 2002). Norovirus infections are 
a leading cause of sporadic and epidemic gastroenteritis across all age groups worldwide (Hoa 
Tran, 2013; de Graaf, 2016). There is an urgent public health need for rapid development of 
novel interventions to prevent the spread of this disease, including prophylactic measures, such 
as vaccines (Esposito, 2020). 
A unique and advantageous immune response elicited by oral vaccination is the induction of 
antibodies derived from mucosal cells. Given that the mucosal route of immunization produces 
superior mucosal immunity compared to injected vaccines, it is hypothesized that VXA-G1.1- 
NN oral vaccine may enable higher degrees of mucosal protection against infection when 
compared to a parenteral immunization method. 
VXA-G1.1-NN is designed to elicit both antibody and T cell responses, mucosally and 
systemically, to Norovirus GI.1 Norwalk VP1. Prior completed Phase 1 studies with the Vaxart 
Vector Adjuvant Antigen Standard Technology (VAASTTM) platform have demonstrated 
protective immunity to viruses, such as norovirus, influenza, and respiratory syncytial virus, with 
both systemic and mucosal immune responses against the antigen of choice (Kim, 2016; Kim, 
2018; Liebowitz, 2020). 
Clinical data is available from 3 Phase 1 studies (VXA- NVV-101, VXA-NVV-102, and 
VXA-NVV-103) which evaluated multiple single- and multi-dose ranging of the monovalent 
vaccine VXA-G1.1-NN in over 200 healthy young adult subjects (18 to 49 years old). These 
studies indicate that the vaccine was tolerated well and generated robust immune responses 
including systemic and mucosal antibodies as well as memory immunoglobulin A (IgA)/ 
immunoglobulin G (IgG). In addition to increase in serum blocking titer fifty assay (BT50) titers, 
vaccine recipients also developed mucosally primed VP1-specific circulating antibody secreting 
cells (ASCs), IgA+ memory B cells expressing gut-homing receptor (α4β7), and fecal IgA, 
indicating substantial and local responses potentially relevant to prevent norovirus infection 
(Kim, 2018). 

VAXART 
Protocol Number: VXA-NVV-105 
 
Amendment 1,  August 25 2021 
 
Page 7 of 62 
 
Over the past year, global efforts for the development of effective COVID-19 vaccines have been 
strongly reliant, among other technologies, on the use of adeno-associated viral vectors (AAV) 
(Callaway, 2020). AAV-based COVID-19 vaccines from AstraZeneca, Johnson & Johnson, and the 
Gamaleya Research Institute of Epidemiology and Microbiology have been granted emergency use 
authorization in many countries worldwide. Contextually, emerging evidence generated in clinical 
settings with the AstraZeneca COVID-19 vaccine (AZD1222) indicates that a 12-week interval 
between vaccine doses might significantly improve efficacy and immunogenicity of AAV-based 
vaccination strategies compared to a shorter 4- or 6-week dosing interval (Voysey et al., 2021; Hung 
and Poland, 2021). Specifically, subjects who received two vaccine doses with a dose interval of at 
least 12 weeks showed neutralizing and anti-SARS-CoV-2 spike IgG antibody responses more than 
two-fold higher than those who received the two-dose regimen at an interval of less than 6 weeks. 
Accordingly, AZD1222 vaccine efficacy increased from 55% (<6-week interval) to 81% with an 
interval of at least 12 weeks. In light of these findings, the current Phase 1b study VXA-NVV-105 is 
designed to assess the safety and immunogenicity of the VXA-G1.1-NN vaccine with a 2-dose 
vaccination schedule using different repeat-dosing intervals (4, 8, or 12 weeks apart) in healthy 
young adults (18 to 55 years old). 
The current phase 1b, open-label, boost-optimization study objectives and endpoints for an 
adenoviral- vector based oral norovirus vaccine (VXA-G1.1-NN) expressing GI.1 VP1 
administered orally to healthy adult volunteers is presented below. 
Objectives and Endpoints (Primary and Secondary) 
Objectives 
Endpoints 
Primary 
• 
To evaluate the immunogenicity of VXA-
G1.1-NN with repeat-dose administration at 
Day 1 and varying boost schedules (Week 
4, 8 or 12 post initial dose) in healthy adults 
aged 18-55, inclusive 
• 
VP1 specific IgA ASC by enzyme-linked 
immunospot (ELISpot) 
• 
Norovirus G1.1 histo-blood group antigen 
(HBGA) blocking antibodies (BT50) 
• 
VP1 specific serum IgG by Mesoscale 
Discovery (MSD) assay 
• 
 
Secondary 
• 
To assess the safety and tolerability of 
VXA- G1.1-NN with repeat-dose 
administration at varying boost schedules 
(Week 4, 8 or 12) in healthy adults aged 
18-55, inclusive 
• 
Frequency, duration, and severity of 
solicited symptoms of reactogenicity 
(local, systemic) for 1 week following 
each dose of study drug 
• 
Frequency, duration, and severity of 
unsolicited serious AEs (SAEs), AEs of 
special interest (AESIs) and New Onset of 
Chronic Illness (NOCIs) through  each Study 
Period (4 weeks post each vaccination) 
 

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Protocol Number: VXA-NVV-105 
 
Amendment 1,  August 25 2021 
 
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Overall Design 
This is an open-label study in healthy adult participants age 18-55 years old. The study will 
enroll 30 subjects to one of three treatment cohorts. 
 
Cohort 1: (4-week boost vaccination) 10 subjects will receive two doses of 1x1010 IU± 0.5 log 
at Day 1 and Week 4 
Cohort 2: (8-week boost vaccination) 10 subjects will receive two doses of 1x1010 IU± 0.5 log 
at Day 1 and Week 8 
Cohort 3: (12-week boost vaccination) 10 subjects will receive two doses of 1x1010 IU± 0.5 log 
at Day 1 and Week 12 
The study will include a screening period, Study Period 1 (Day 1 to 4 weeks post initial 
vaccination), Study Period 2 (4 Weeks from second vaccination will be initiated at Week 4 for 
Cohort 1, Week 8 for Cohort 2 and Week 12 for Cohort 3), and a follow-up period of 6 months 
post second vaccination in each cohort. Study assessments will be conducted as shown in the 
Schedule of Activities (SoA) in Section 1.2 (Table 2). In addition, participants will be contacted 
by phone between site visits to monitor for safety as specified in the SoA. 
After signing an informed consent, participants will undergo screening assessments to determine 
study eligibility within a 45-day screening period. 
Eligible participants will be enrolled and receive their first dose of study vaccine on Day 1. 
During the Active study period, participants will record any potential symptoms of 
reactogenicity daily for 1  week post each vaccination, administered on Day 1 and Week 4, 8 
or 12, depending on cohort assignment, using a Solicited Symptom Diary. Participants will 
return to the site as specified in the SoA to have safety assessments and samples collected for 
evaluation of immunogenicity. 
At the participant’s second vaccination visit (Week 4, 8 or 12 depending on Cohort assignment) 
they will have pre-dose safety assessments to determine eligibility to continue with the second 
vaccination. Additionally, female participants of childbearing potential must have a negative 
pregnancy test before receiving their second vaccination. Participants deemed ineligible for the 
second vaccination due to acute illness or new medical condition may be re-assessed, and if the 
condition resolves, may have a delayed second vaccination within 1 week of their scheduled 
vaccination Visit (+7 days window from Week 4, 8 or 12 depending on Cohort assignment). 
Participants with a delayed second vaccination will follow the delayed schedule through the rest 
of their Active Period as specified in the SoA. 
If a subject remains ineligible for the second vaccination, they will complete an Early 
Termination visit and then enter the scheduled follow-up period per Cohort assignment as 
outlined in the SoA (1.2).   
All participants will enter the follow-up period 4 weeks after their last vaccination and will be 
monitored for SAEs including AESIs and NOCIs through End of Study. Participants will also 
have samples collected for evaluation of immunogenicity as specified in the SoA. 
 

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Protocol Number: VXA-NVV-105 
 
Amendment 1,  August 25 2021 
 
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Intervention Group and Number of Participants 
Table 1 
Treatment Arm, Doses and Sample Size 
Group 
Study Drug 
Dose (IU ±0.5 log) 
No. of Doses 
Dosing Schedule 
No. of Subjects 
Cohort 1 
VXA-G1.1-NN 
1x1010 
2 
Day 1 & Week 4a 
10 
Cohort 2 
VXA-G1.1-NN 
1x1010 
2 
Day 1 & Week 8a 
10 
Cohort 3 
VXA-G1.1-NN 
1x1010 
2 
Day 1 & Week 12a 
10 
Total 
30 
a Subjects not eligible for the second dose (within the 7-day dosing window) will immediately enter the follow-up period. 
 
 
 
 
 
 
Study Duration for Each Participant 
For each subject, study participation is expected to last as follows: 
 
Study Period 
Cohort 1 
(Day 1 and Week 4) 
Cohort 2 
(Day 1 and Week  8) 
Cohort 3 
(Day 1 and Week 12) 
Screening Period: 
45 days 
45 days 
45 days 
Study Period 1: 
4 weeks (Day 1 – Week 4) 4 weeks (Day 1 – Week 4) 4 weeks (Day 1 – Week 4) 
Study Period 2: 
4 weeks (Week 4 – 8) 
4 weeks (Week 8 – 12) 
4 weeks (Week 12 – 16) 
Follow-Up Period: 
6 months following boost 6 months following boost 
6months following boost 
Total Duration 
7 Months 
8 Months 
9 Months 
 
Safety Monitoring Committee (SMC): No 

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Protocol Number: VXA-NVV-105 
 
Amendment 1, 25 August 2021  
 
 
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1.2  Schedule of Activities 
Active Period 
 
Screen Study Period 1 – Cohorts 1, 2, 3 
 
 
 
 
Study Period 2 – Cohort 1 
 
 
 
 
Study Period 2 – Cohort 2 
 
 
 
 
Study Period 2 – Cohort 3 
Study Day 
-45d to 
–1 d 
Day 1  
(Wk 0) 
Day 8  
(Wk 1) 
Day 29  
(Wk 4) 
Day 36  
(Wk 5) 
Day 57  
(Wk 8) /ET1 
Day 64  
(Wk 9) 
Day 85 
(Wk 12)/ET2 
Day 92  
(Wk 13) 
Day 113  
(Wk16)/ET3 
Visit Window (days) 
 
n/a 
0 
±2 
0 
±2 
0 
±2 
0 
±2 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
X 
 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
Stool for occult blood 
X 
 
 
 
 
 
 
 
 
 
Blood Sample (HBsAg, HCV, 
HIV) 
X 
 
 
 
 
 
 
 
 
 
Urine drug screen 
X 
 
 
 
 
 
 
 
 
 
Alcohol Testing 
X 
 
 
 
 
 
 
 
 
 
Pregnancy Testa 
X 
X 
 
X1 
 
X2 
 
X3 
 
 
Physical examination 
X 
Xb 
Xb 
Xb 
Xb 
Xb 
Xb 
Xb 
Xb 
Xb 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Safety laboratory tests 
X 
Xc 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
COVID vaccination status 
X 
 
 
 
 
 
 
 
 
 
Vaccination 
 
X
 
X1, d,e 
 
X,2, d,e
 
X3, d,e
 
 
Dispense Solicited Symptom Diary 
 
X1,2,3
 
X1
 
X2
 
X3
 
 
Review & Collect Solicited 
Symptom Diary 
 
 
X 
 
X1 
 
X2 
 
X3 
 
Review prior & concomitant 
medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Query for AEs, SAEs, AESIs and 
NOCIs 
 
X 
X 
X 
X1,f 
X1,f 
X2,f 
X2,f 
X3,f 
X3,f 
Sample Collection Immunogenicity Assessments 
Serum  
 
X1,2,3,g
 
X1,2,3
 
X1,2
 
X2,3
 
X3 
Whole blood (Flow Based) 
 
X1,2,3
X1,2,3 
X1
X1 
X2
X2 
X3
X3 
 
Whole blood (PBMC) 
 
X1,2,3
X1,2,3 
X1
X1 
X2
X2 
X3
X3 
 
Nasal Swab (Sam Device) 
 
X1,2,3
 
X1,2,3
 
X1,2
 
X2,3
 
X3 
Saliva Sample 
 
X1,2,3
 
X1,2,3
 
X1,2
 
X2,3
 
X3 

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Protocol Number: VXA-NVV-105 
 
Amendment 1, 25 August 2021  
 
 
Page 11 of 62 
 
AE, adverse vent; AESI, Adverse event of special interest; EOS, End of Study; ET, Early Termination (7.2); HCV, Hepatitis C Virus; HIV, Human Immunodeficiency Virus; NP, 
Nasopharyngeal; NOCI, New Onset of Chronic Illness; PBMC, peripheral blood mononuclear cells; SAE, serious adverse event. 
1 = Cohort 1; 2 = Cohort 2; 3  = Cohort 3. 
a For women of childbearing potential. Test at Day 1 and at second dose (boost). Test can be serum or urine test. 
b Targeted. 
c If screening lab tests are performed within 2 days prior to dosing, no need to repeat at Day 1. 
d Assess eligibility to receive second dose. Participants with acute illness or new medical condition may be re-assessed, and if the condition resolves, have a delayed 2nd dose 
within 1 week of scheduled visit. 
e If participants are not eligible to receive their 2nd dose, they immediately enter the follow-up period. 
f AEs will only be collected for 4 weeks following each study drug administration. 
g.An aliquot of serum collected at baseline will be stored for testing (e.g. Platelet Factor 4 [PF4] antibody ELISA) should an AESI related to blood clots be reported anytime during 
the study period. 
 
 
Follow-Up Period 
 
COHORT 1 
COHORT 2 
COHORT 3 
Study Day 
Months 3, 4, 
5, 6 
Month 7 
(Wk 28)/ EOS 
Months 4, 
5, 6, 7  
Month 8 
(Wk 32)/EOS  
Months 5, 6, 7, 
8 
Month 9 (Wk 36)/ 
EOS 
Telephone Visit 
  X 
X 
 
X 
 
Visit Window (days) 
±7 
±7 
±7 
±7 
±7 
±7 
Query for SAEs, AESIs and 
NOCIs  
X 
X 
X 
X 
X 
X 
Sample Collection Immunogenicity Assessments 
Serum  
X 
X 
 
X 
Whole blood (Flow Based) 
 
 
 
 
Whole blood (PBMC)a 
X 
X 
 
X 
Nasal Swab (Sam Device) 
X 
X 
 
X 
Saliva  
X 
X 
 
X 
AE, adverse event; AESI, Adverse event of special interest; EOS, End of Study; ET, Early Termination;  HCV, Hepatitis C Virus; HIV, Human Immunodeficiency Virus; NP, 
Nasopharyngeal; NOCI, New Onset of Chronic Illness; PBMC, peripheral blood mononuclear cells; SAE, serious adverse event. 
a Optional. 
 
 

VAXART 
Protocol Number: VXA-NVV-105 
 
Amendment 1, 25 August 2021 
 
Page 12 of 62 
 
 
2. 
INTRODUCTION 
 
2.1. Study Rationale 
VXA-G1.1-NN is an E1/E3-deleted, replication-incompetent, adenovirus 5 (Ad5) vaccine 
vectors designed for use as an oral vaccine for the prevention of noroviral gastroenteritis caused 
by norovirus genogroups GI.1. The monovalent vaccine vector encodes the full-length of viral 
protein 1 (VP1) gene of Norwalk virus (Norovirus GI.1). The adjuvant consists of a double- 
stranded RNA Toll-like receptor 3 (TLR3) agonist which enhances immune induction to 
expressed antigen in the gut mucosa. 
Noroviruses are a genetically diverse group of small, non-enveloped, single-stranded positive 
sense RNA viruses belonging to the Caliciviridae family (Bresee, 2002). Norovirus infections are 
a leading cause of sporadic and epidemic gastroenteritis across all age groups worldwide (Hoa 
Tran, 2013; de Graaf, 2016). There is an urgent public health need for rapid development of 
novel interventions to prevent the spread of this disease, including prophylactic measures, such 
as vaccines (Esposito, 2020). 
A unique and advantageous immune response elicited by oral vaccination is the induction of 
antibodies derived from mucosal cells. Given that the mucosal route of immunization produces 
superior mucosal immunity compared to injected vaccines, it is hypothesized that VXA-G1.1- 
NN oral vaccine may enable higher degrees of mucosal protection against infection when 
compared to a parenteral immunization method. 
VXA-G1.1-NN is designed to elicit both antibody and T cell responses, mucosally and 
systemically, to Norovirus GI.1 Norwalk VP1. Prior completed Phase 1 studies with the Vaxart 
Vector Adjuvant Antigen Standard Technology (VAASTTM) platform have demonstrated 
protective immunity to viruses, such as norovirus, influenza, and respiratory syncytial virus, with 
both systemic and mucosal immune responses against the antigen of choice (Kim, 2016; Kim, 
2018; Liebowitz, 2020). 
Clinical data is available from 3 Phase 1 studies (VXA- NVV-101, VXA-NVV-102, and 
VXA-NVV-103) which evaluated multiple single- and multi-dose ranging of the monovalent 
vaccine VXA-G1.1-NN in over 200 healthy young adult subjects (18 to 49 years old). These 
studies indicate that the vaccine was tolerated well and generated robust immune responses 
including systemic and mucosal antibodies as well as memory immunoglobulin A (IgA)/ 
immunoglobulin A (IgG). In addition to increase in serum blocking titer fifty assay (BT50) titers, 
vaccine recipients also developed mucosally primed VP1-specific circulating antibody secreting 
cells (ASCs), IgA+ memory B cells expressing gut-homing receptor (α4β7), and fecal IgA, 
indicating substantial and local responses potentially relevant to prevent norovirus infection 
(Kim, 2018). 
The current Phase 1b study is designed to assess the immunogenicity of VXA-G1.1-NN with 
repeat-dose administration at Day 1 and 2nd vaccination at Weeks 4, 8 or 12 (depending on 
Cohort assignment) in healthy adults aged 18-55, inclusive, with varying boost schedules.  
 
2.2.  Background 
Noroviruses are a leading cause of foodborne disease and outbreaks of gastroenteritis worldwide 
and are responsible for substantial morbidity, mortality, and healthcare costs (Bányai, 2018). The 

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virus affects people of all ages; however, the incidence of disease is higher in younger children 
and in adults ≥65 years old (Lopman, 2016; Esposito, 2020). Noroviruses are highly infectious 
with major mode of transmission by fecal-oral spread, usually via contaminated food or water 
(Teunis, 2008; de Graaf, 2016; Gaythorpe, 2018). The incubation period of norovirus is 10-51 
hours. 
Noroviruses are genetically diverse viruses. Genogroups I, II and IV are human-transmitted. 
Genogroup I and II account for the majority of norovirus outbreaks (Vega, 2014). Each 
genogroup is further divided into genotypes based on the similarity of the amino acid sequence 
of the major viral capsid protein, VP1. Genotypes GI.1 and GII.4 represent the genogroups 
responsible for most outbreaks and the majority of the disease burden globally (Lopman, 2016). 
Norovirus causes extensive morbidity with clinical symptoms of nausea, vomiting, non-bloody 
diarrhea, and abdominal cramps. Fever, headache, and body aches have been reported as well. 
These symptoms usually last 2-4 days. Additionally, asymptomatic infections are estimated to 
occur in approximately one-third of infected people. Currently no specific therapy exists for 
norovirus gastroenteritis. The standard treatment is oral rehydration with fluids and electrolytes 
(Glass, 2009). There are currently no licensed vaccines for norovirus. 
Norovirus is an enteric pathogen and infects the epithelial cells of the small intestine. Vaxart’s 
platform is based on oral delivery of the vaccine to the intestinal mucosa, which is analogous to 
the natural route of norovirus infection and entry. Human and animal experience with Vaxart’s 
orally administered platform has demonstrated that substantial transgene specific intestinal IgA 
responses can be generated in addition to systemic IgG responses to the expressed antigen 
(influenza HA and norovirus VP1). These platform attributes may allow for better protection 
against norovirus infection than an injected protein-based vaccine. 
As indicated, VXA-G1.1-NN was well tolerated in 3 Phase 1 studies and generate robust 
immune responses. In study VXA-NVV-101, the primary immunological endpoint (increase in 
BT50 titers) was met in the high-dose group (P = 0.0003), with 78% showing a ≥2-fold rise in 
titers after a single immunization (Kim, 2018). Statistically significant increases in geometric 
mean titers were also seen in Study VXA-NVV-103 with VXA-G1.1-NN compared with placebo 
(p=0.0008), with 43% of subjects showing a ≥4-fold increase in titers post vaccination. 
A detailed description of the chemistry, pharmacology, efficacy, and safety of VXA-G1.1-NN is 
provided in the Investigator’s Brochure (IB). 
 
2.3.  Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of VXA-G1.1-NN may be found in the IB. 
 
 
 
 
 
 
 
 
 
 

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Table 3 
Risk Assessment 
Clinically Significant Risk 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Study Drug VXA-G1.1-NN 
Potential for vaccine 
related 
hypersensitivity, 
including 
anaphylaxis 
Similar to other drugs, vaccines have the 
potential to cause allergic reactions. 
Vaccine components including immunizing 
antigens, adjuvants, culture derived proteins 
(e.g., gelatin) and other agents may have the 
potential to cause complications. 
Monitor participants for any 
allergic reactions and onset 
of new illness during the 
active and follow-up period. 
Potential for systemic 
and gastrointestinal 
events (fever, 
headache, myalgia, 
abdominal pain, 
anorexia, nausea, 
vomiting, vomiting, 
diarrhea, and 
malaise/fatigue) 
following vaccination. 
These systemic events are common adverse 
reactions seen with other vaccines, as noted in 
the FDA Center for Biologics Evaluation and 
Research (CBER) guidelines on toxicity 
grading scales for healthy adult volunteers 
enrolled in preventive vaccine clinical studies. 
Given the route of delivery and mechanism of 
action for an ingestible vaccine, some 
additional GI events may 
also be observed. 
Actively monitor systemic 
and GI-associated reactions 
(solicited symptoms) for 7 
days following each study 
drug administration. 
Potential for severe 
events of thrombosis in 
combination with 
thrombocytopenia 
(Thrombosis with 
thrombocytopenia 
syndrome, TTS), in 
some cases 
accompanied by 
bleeding, as reported in 
rare cases following 
vaccination with two 
injected adenovirus-
vectored COVID-19 
vaccines. 
Severe cases of TTS have been reported 
following vaccination with two adenovirus-
vectored COVID-19 vaccines: the 
AstraZeneca COVID-19 vaccine (ChAdOx1; 
replication-deficient chimpanzee adenoviral 
vector ChAdOx1) and the Johnson and 
Johnson COVID-19 vaccine (Ad26.COV2.S; 
replication-incompetent adenovirus serotype 
26 vector). Reports include cases of 
thrombocytopenia in combination with arterial 
and venous thrombosis at unusual sites, such 
as cerebral venous sinus thrombosis (CVST) 
and splanchnic vein thrombosis, as well as 
more common sites such as veins of the lower 
extremity. Onset of symptoms associated with 
these AEs has typically occurred within 4 
weeks after vaccination, and most commonly 
within 1-2 weeks after vaccination, although 
some cases have been reported with later onset 
of symptoms. Cases have been reported mostly 
in women under 60 years of age, although 
cases have also been reported in men and in 
women older than 60 years. Some of these 
cases have been fatal. A causal relationship 
between these events and the two vaccines is 
considered plausible. The exact patho-
physiology of TTS is still under investigation. 
At this time, a mechanism related to the 
adenovirus vectors cannot be excluded. 
Exclude enrollment of 
participants at higher risk of 
clotting events per review 
of medical history, physical 
exam and safety laboratory 
tests at screening. Actively 
monitor for signs and 
symptoms of 
thromboembolism and/or 
thrombocytopenia. Study 
participants should be 
instructed to seek 
immediate medical 
attention if they develop 
symptoms including, but 
not limited to, shortness of 
breath, chest pain, leg pain 
and/or swelling, persistent 
abdominal pain, severe or 
persistent headaches, 
blurred vision or other 
vision changes, mental 
status changes or seizures, 
petechia, purpura beyond 
the site of vaccination, 
and/or easy bruising/ 
bleeding. 

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2.3.1.  Benefit Assessment 
Benefits to individual participants may include receipt of a potentially efficacious norovirus 
vaccine. Clinical data from Phase 1 studies demonstrated that VXA-G1.1-NN generated robust 
immune responses. 
 
2.3.2.  Overall Benefit/Risk Conclusion 
Taking into account the measures to be utilized to minimize risk to participants taking part in this 
study, the potential risks identified in association with the VXA-G1.1-NN vaccine for the 
prevention of norovirus infection are justified as by the anticipated benefits that may be afforded 
to healthy stable adult participants. 

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3.  OBJECTIVES AND ENDPOINTS 
 
Objectives 
Endpoints 
Primary 
• To evaluate the immunogenicity of 
VXA-G1.1-NN with repeat-dose 
administration at Day 1 and varying 
boost schedules (Week 4, 8 or 12 
post initial dose) in healthy adults 
aged 18-55, inclusive 
• VP1 specific IgA ASC by enzyme-linked 
immunospot (ELISpot) 
• Norovirus G1.1 histo-blood group antigen 
(HBGA) blocking antibodies (BT50) 
• VP1 specific serum IgG by Mesoscale 
Discovery (MSD) assay 
 
Secondary 
• To assess the safety and tolerability 
of VXA- G1.1-NN with repeat-dose 
administration at varying boost 
schedules (Week 4, 8 or 12) in 
healthy adults aged 18-55, inclusive 
• Frequency, duration, and severity of 
solicited symptoms of reactogenicity 
(local, systemic) for 1 week following 
each dose of study drug 
• Frequency, duration, and severity of 
unsolicited serious AEs (SAEs), AEs of 
special interest (AESIs) and New Onset of 
Chronic Illness (NOCIs) through  each Study 
Period (4 weeks post each vaccination) 
Exploratory 
• To assess additional safety 
parameters 
• Occurrence of clinically significant 
abnormalities in laboratory parameters 
(chemistry, hematology and urinalysis) at 1 
week after each study drug dose and in vital 
signs immediately following each dose 
• To assess long-term safety of VXA- 
G1.1-NN through 6 months after 
last vaccination 
• Frequency, duration, and severity of all 
SAEs, AESIs and NOCIs  through 6 months 
after last vaccination  
• To assess additional immunogenicity 
parameters of VXA-G1.1-NN 
• VP1 specific IgG ASC 
• VP1 specific serum IgA 
• Ad5 neutralizing antibodies 
• VP1 specific IgG and IgA memory B cells 
• B cell immunophenotyping 
• Saliva VP1 IgA 
• Nasal Swab VP1 IgA 
(Note: Additional exploratory 
immunogenicity assays may also be 
performed to further evaluate the activity  of 
the VXA-G1.1-NN vaccine candidate) 

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4. OVERALL STUDY DESIGN 
This is an open-label, boost-optimization study of an adenoviral- vector based oral norovirus 
vaccine (VXA-G1.1-NN) expressing GI.1 VP1 administered orally to health adult participants 
18-55, inclusive. This study will enroll approximately 30 participants in three cohorts stratified 
by varying boost vaccination schedules. 
The study will include a Screening period, Active study period through 4 weeks post last 
vaccination dose (Week 8 for Cohort 1, Week 12 for Cohort 2 and Week 16 for Cohort 3), and 
a Follow-up period of 6 months post vaccination (Month 7 for Cohort 1, Month 8 for Cohort 2 
and Month 9 for Cohort 3). Study assessments will be conducted as shown in the SoA in 
Section 1.2 (Table 2). In addition, participants will be contacted monthly by phone between 
site visits to monitor for safety as specified in the SoA. 
After signing an informed consent, participants will undergo screening assessments to determine 
study eligibility over a 45-day screening period. 
On Day 1, participants will be enrolled sequentially in order of eligibility. Participants may be 
assigned to cohorts based on their availability for the second dose (boost). Cohorts 3 and 2 may be 
enrolled prior to Cohort 1 to optimize the overall study timeline. 
 
Group 
Study Drug 
Dose (IU ±0.5 log) 
Doses 
Dosing Schedule 
Subjects 
Cohort 1 
VXA-G1.1-NN 
1x1010 
2 
Day 1 & Week 4 
10 
Cohort 2 
VXA-G1.1-NN 
1x1010 
2 
Day 1 & Week 8 
10 
Cohort 3 
VXA-G1.1-NN 
1x1010 
2 
Day 1 & Week 12 
10 
Total 
30 
 
Eligible participants will be enrolled to receive their first dose of study vaccine on Day 1. 
During the Active period, participants will record symptoms of reactogenicity daily for 1 week 
post each vaccination, administered based on Cohort assignment, using a Solicited Symptom 
Diary. Participants will return to the site as specified in the SoA to have safety assessments and 
samples collected for evaluation of immunogenicity. 
Additionally, female participants of childbearing potential must have a negative pregnancy test 
before their second dose of study drug. Participants deemed unsuitable for the second dose due 
to acute illness or new medical condition may be re-assessed, and if the condition resolves, may 
have a delayed second dose administered within 1 week of their originally scheduled 
second-dose visit (+7 days window). Participants with a delayed second study drug 
administration will follow the delayed schedule through their active period. 
All participants will enter the follow-up period 4 weeks after their second dose and will be 
monitored for SAEs, including AESI and NOCI, through End of Study. Participants will also be 
evaluated for immunogenicity as specified in the SoA. 
Any participants who are not eligible to receive the second study drug administration will enter 
the follow-up period at that visit rather than receiving the second dose and will be monitored 
for safety and evaluated for immunogenicity through their End of Study as specified in the 
SoA. 

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4.1. Scientific Rational for Study Design 
Emerging evidence generated in clinical settings with the AstraZeneca COVID-19 vaccine 
(AZD1222) indicates that a 12-week interval between vaccine doses might significantly 
improve efficacy and immunogenicity of AAV-based vaccination strategies compared to a 
shorter 4- or 6-week dosing interval (Voysey et al., 2021; Hung and Poland, 2021). In light of 
these findings, the current Phase 1b study is designed to assess the safety and immunogenicity 
of the VXA-G1.1-NN vaccine with a 2-dose vaccination schedule using different repeat-dosing 
intervals (4, 8, or 12 weeks apart) in healthy young adults (18 to 55 years old). 
4.2. Justification for Varying Dose Schedules 
Based on the safety results observed in completed and ongoing studies with prior vaccines 
utilizing the VAAST platform, the multiple dosing schedules of VXA-G1.1-NN selected for 
this Phase 1b study are second dose at 4 weeks for Cohort 1, 8 weeks in Cohort 2 and 12 
weeks at Cohort 3, with participants receiving at 1x1010 IU± 0.5 at both visits. 
Over 200 subjects have been immunized with multiple Vaxart recombinant adenovirus serotype 
5 (rAd5) vaccine candidates at 1x1010 IU and a similar number of subjects have been immunized 
at 1x1011 IU. These dose levels demonstrated a favorable safety profile and generated strong 
immune responses. Repeat dosing with the VXA-G1.1-NN oral vaccine has previously been 
tested at doses up to 1x1011 IU at Days 1 and 29 in two prior trials (VXA-G11-101 and VXA-
G11-102). These studies showed the vaccine to be safe and immunogenic. The current study will 
evaluate different dosing schedules of VXA-G1.1-NN in healthy adults at doses of 1x1010 IU. 
4.3.  Study Duration 
For each participant participation is expected to last as follows: 
Study Period 
Cohort 1 
(Day 1 and Week 4) 
Cohort 2 
(Day 1 and Week  8) 
Cohort 3 
(Day 1 and Week 12) 
Screening Period: 
45 days 
45 days 
45 days 
Study Period 1: 
4 weeks (Day 1 – Week 4) 4 weeks (Day 1 – Week 4) 4 weeks (Day 1 – Week 4) 
Study Period 2: 
4 weeks (Week 4 – 8) 
4 weeks (Week 8 – 12) 
4 weeks (Week 12 – 16) 
Follow-Up Period: 
6 months following boost 6 months following boost 6 months following boost 
Total Duration 
7 Months 
8 Months 
9 Months 
 
4.4.  End of Study Definitions 
A participant is considered to have completed the study if they complete through the study 
Active and Follow-Up Period for their Cohort.  
 
4.5.  Safety and Final Database Lock 
Following completion of the Active Period by all Cohorts, the database will be cleaned and 
locked. The Clinical Study Report (CSR) will be written based on the last Active Visit dataset 
(Cohort 1- Week 8; Cohort 2- Week 12, Cohort 3 – Week 16). 
Following completion of End of Study visit for all subjects, the safety database will be cleaned and 
locked and data collected during the Follow-Up Period will be amended to the Study CSR. 

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5. 
ELIGIBILITY CRITERIA 
 
5.1.  Inclusion Criteria 
To be eligible for this study, participants must meet all the following: 
Age 
1. 18 to 55 years old inclusive at the time of signing the Informed Consent Form (ICF). 
Type of Participants 
2. 
General good health, without significant uncontrolled medical illness, based on medical 
history, physical examination, vital signs, and clinical laboratories (CBC, chemistry, and 
urinalysis) as determined by the investigator in consultation with the Research Monitor and 
Sponsor  
3. Body mass index (BMI) between 17 and 35 kg/m2 at screening 
4. Available for all planned visits and phone calls, and willing to complete all protocol- 
defined procedures and assessments (including ability and willingness to swallow 
multiple small enteric-coated tablets per study dose). 
Gender and Reproductive Considerations 
5. Male or female participants 
Contraception use by men or women should be consistent with local regulations regarding the methods 
of contraception for those participating in clinical studies. Refer to Appendix 4 (Section 10.4) 
a. Female participants must provide a negative pregnancy test at each required visit and 
fulfill one of the following criteria: 
• At least 1 year post-menopausal (defined as amenorrhea for ≥12 consecutive 
months prior to Screening without an alternative medical cause). 
• Women under 60 years will need to verify post-menopausal status via a 
follicle-stimulating hormone (FSH) test if another option to prevent potential 
pregnancy will not be utilized for 30 days prior to baseline vaccination and 
until 60 days after the last vaccination. 
• Surgically sterile 
• Use of oral, implantable, transdermal or injectable contraceptives for 30 days 
prior to initial vaccination and until 60 days after the last vaccination. The 
form of contraception must be approved by the Investigator 
• A reliable form of contraception must be approved by the Investigator (e.g., 
double barrier method, Depo-Provera, intrauterine device, Norplant, oral 
contraceptives, contraceptive patches). 
• Not be sexually active (abstinent) or be in a relationship with partner who is 
sterile (must be discussed with site staff and documented). 
Informed Consent 
6. Capable of giving signed informed consent which includes compliance with the requirements 
and restrictions listed in the ICF and in this protocol. 

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5.2.  Exclusion Criteria 
The participants must be excluded from participating in the study if they meet any of the 
following: 
 
Medical Conditions 
1. 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 
2. Cancer, or received treatment for cancer, within past 3 years (excluding basal cell 
carcinoma or squamous cell carcinoma) 
3. Presence of immunosuppression or medical condition possibly associated with impaired 
immune responsiveness, including diabetes mellitus 1 and 2 
4. History of irritable bowel disease or other 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 
b. Malignancy 
c. Malabsorption 
d. Pancreaticobiliary disorders 
e. Irritable bowel syndrome 
f. Inflammatory Bowel Disease 
g. Surgical Resection 
h. GERD 
i. Hiatal Hernia 
j. Peptic Ulcer 
(History of cholecystectomy is not exclusionary) 
5. History of any form of angioedema 
6. History of serious reactions to any vaccination such as anaphylaxis, respiratory 
problems, hives or abdominal pain 
7. Diagnosed bleeding disorder or significant bruising or bleeding difficulties that could 
make blood draws problematic 
8. Any condition that resulted in the absence or removal of the spleen 
9. Acute disease within 72 hours prior to vaccination defined as the presence of a moderate 
or severe illness (as determined by the Investigator through medical history and physical 
exam). (Assessment may be repeated during screening period.) 
10. Presence of a fever ≥ 38oC measured orally at baseline (Assessment may be repeated 
during screening period) 
11. Any significant hospitalization within the last year which in the opinion of the 
Investigator or Sponsor could interfere with study participation. 
12. Any other condition that in the clinical judgment of the investigator would jeopardize the 

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safety or rights of a participant taking in the study, would render the participant unable to 
comply with the protocol or would interfere with the evaluation of the study endpoints 
Diagnostic Assessments 
13. Positive human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg) or 
hepatitis C virus (HCV) tests at the screening visit 
14. Positive urine drug screen for drugs of abuse at screening 
15. Positive breath or urine alcohol test at screening and baseline 
Prior/Concurrent Therapy 
16. Receipt of a licensed vaccine within 14 days prior to baseline vaccination or planned 
administration during the study active period (4 weeks post each study vaccination). 
17. Use of antibiotics, proton pump inhibitors, H2 blockers or antacids within 7 days prior to 
study drug administration or planned use during the active study period  
18. Use of medications known to affect the immune function (e.g., systemic corticosteroids 
and others) within 2 weeks before study drug administration or planned use during the 
active study period  
19. Daily use of nonsteroidal anti-inflammatory drugs within 7 days prior to study drug 
administration or planned use during the active study period  
20. Administration of any investigational vaccine, drug or device within 8 weeks preceding 
study drug administration (Day 1), or planned use within the duration of the study 
Other Exclusions 
21. Donation or use of blood or blood products within 30 days prior to study drug 
administration or planned donation during the active study period  
22. History of drug, alcohol or chemical abuse within 1 year of screening 
23. History of hypersensitivity or allergic reaction to any component of the investigational 
vaccine, including but not limited to fish gelatin 

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5.3.  Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently entered in the study. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure candidates to meet the Consolidated Standards of 
Reporting Trials (CONSORT) publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details, eligibility criteria, 
and any SAE. 
Re-screening/re-assessment outside the screening period will be possible on a case-by-case basis 
following Sponsor approval. Participants allowed to be re-screened will be assigned a new 
screening number; such participants will be determined a permanent screen failure after the 
second screening determines the participant is ineligible. 

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6. 
STUDY DRUG, CONCOMITANT THERAPY AND LIFE-STYLE 
CONSIDERATIONS 
Study drug is defined as any investigational intervention(s), marketed product(s), placebo, or 
medical device(s) intended to be administered to a study participant according to the study 
protocol. 
 
6.1.  Study Drug Administration 
VXA-G1.1-NN is an E1/E3-deleted, replication-incompetent, Ad5 vaccine vectors designed for 
use as an oral vaccine. The monovalent vaccine vector encodes the full-length of VP1 gene of 
Norovirus GI.1. The adjuvant consists of a double-stranded RNA TLR3 agonist which enhances 
immune induction to expressed antigen in the gut mucosa. 
Table 4 
VXA-G1.1-NN Study Drug 
 
Intervention Name 
VXA-G1.1-NN 
Type 
Biologic 
Dose Formulation 
Enteric-coated tablets 
Unit Dose Strength(s) 
6.7x109 IU per tablet 
(Drug Product Lot: DP-05.19004) 
Dosage Level(s) 
1x1010 IU ± 0.5 log 
(2 tablets of VXA-G1.1-NN (Lot DP-05.19004) will be dispensed to 
deliver each dose) 
Route of Administration 
Oral 
Administration 
instructions 
Participants should fast and refrain from ingesting solid food for at least 
8 hours prior to oral dosing. A trained member of the site study staff 
will dispense the tablet(s) constituting their assigned dose to the 
participant. The participants will swallow the tablets with 360 to 
480 mL of water or clear fruit juice (acidic, such as cranberry juice) 
followed by a light snack (e.g., crackers) at time of dosage administration 
to aid in tablet transit out of the stomach. Normal food consumption may 
resume 90 minutes after dosing. For more information refer to the Study 
Pharmacy Manual. 
Sourcing 
Study drug will be provided to the site by the Sponsor or 
designated representative. 
Packaging and Labeling 
The tablets are packaged into foil-sealed, high-density polyethylene 
(HDPE) screw-cap containers with 10 tablets per bottle. 
All packaging and labeling operations for study drug will be performed 
according to Good Manufacturing Practices (GMP) for Medicinal 
Products and the relevant regulatory requirements. Label text for the 
study drug bottle will at a minimum include name of the manufacturer, 
the protocol number, the name of the product, the lot number of the 

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Intervention Name 
VXA-G1.1-NN 
product, the concentration of the vaccine, the date of manufacturing or 
expiration. 
The final dispensing container (cup or secondary bottle) will be 
appropriately labeled with the participant’s unique identifier, the 
time/date of dose preparation within the pharmacy and additional 
information as deemed necessary per the site’s standard operating 
procedures. 
Storage Condition 
VXA-G1.1-NN vaccine tablets will be stored at 2 to    8°C at the 
clinical site until ready for use. Tablets should not be frozen. Do not 
use and contact Sponsor if DP tablets have been frozen. 
 
6.2.  Compliance of Study Drug 
Participants will receive study drug directly from the investigator or designee, under medical 
supervision. The date and time of each dose administered in the clinic will be recorded in the 
source documents and recorded in the eCRF. The study drug and study participant 
identification will be confirmed at the time of dosing by a member of the study site staff other 
than the person administering the study drug. 
 
6.2.1 Dose Adjustments/Modifications/Delays 
Dose adjustments and or modifications are not planned or allowed under this clinical protocol. 
All participants should receive the full dose of 1x1010 IU ± 0.5 log at the protocol-defined study 
visits by Cohorts as specified in the SoA after meeting eligibility. Any modification from this 
schedule or planned dose should be recorded as a protocol violation and reported to the Sponsor (or 
designee). 
 
6.3. Handling and Accountability 
1. The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for study drug received and any discrepancies are reported and 
resolved before use of study drug. 
2. Only participants enrolled in the study may receive study drug and only authorized site 
staff may supply or administer study drug. All bottles of study drug must be stored in a 
secure, environmentally controlled, and monitored (manual or automated) area in 
accordance with the labeled storage conditions with access limited to the investigator and 
authorized site staff. 
3. The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study drug accountability, reconciliation, and record maintenance (i.e., 
receipt, reconciliation, and final disposition records). 
4. At the end of the study active period, the monitor will conduct a final drug 
reconciliation for all participants and the study site overall. All records of study drug 

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administration, accountability records and study drug disposition records will be 
examined and reconciled by the study monitor. Further details will be provided in the 
Study Pharmacy Manual. 
Further guidance and information for the final disposition of unused study drug are provided in 
the Pharmacy Manual. 
 
6.4. Treatment of Overdose 
Any overdose of study drug should be recorded in the eCRF (including quantity of the excess 
dose and the duration of the overdose). AEs associated with an overdose or incorrect 
administration of study drug should be recorded in the AE eCRF. An overdose will not be 
considered an SAE unless the outcome of the overdose meets seriousness criteria. 
There is no specific management of an overdose of VXA-G1.1-NN. Participants should be 
closely monitored for toxicities and managed appropriately. 
6.5.  Concomitant Therapy 
Concomitant medication is defined as any prescription or over-the-counter preparation. 
Use of concomitant medication from 4 weeks before Day 1 through 4 weeks after the last dose 
administration (completion of Active Study period) must be recorded onto the eCRF from the 
participant’s medical file along with: 
• Reason for use 
• Dates of administration including start and end dates 
• Dosage information including dose and frequency 
Medications for pre-existing medical conditions or required for a medical condition during the 
study are allowed if not considered exclusionary. 
The Sponsor's Medical Monitor (or designee) should be contacted if there are any questions 
regarding concomitant or prior therapy. 
 
6.5.1. Prohibited Concomitant Medication 
Medications specifically prohibited in the exclusion criteria are not allowed during the Active 
Study period (Section 5.2 prior/concurrent therapy), unless deemed medically necessary by the 
Investigator. 
 
6.6.  Intervention after the End of the Study 
No additional intervention is planned beyond the end of the study. 
 
7. 
DISCONTINUATION OF STUDY DRUG AND 
PARTICIPANT WITHDRAWAL FROM STUDY 
 
7.1.  Discontinuation of Study Drug 
In some instances, it may be necessary for a participant to permanently discontinue study drug 
(that is, not receive the second vaccination).  

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Permanent discontinuation of study drug does not mean withdrawal from the study, and the 
participant will be encouraged to remain in the study and continue to complete all study follow- 
up visits.  
Participants may discontinue or be discontinued from study drug at any time. A participant may 
discontinue study drug for reasons including but not limited to: 
• Adverse event 
• Death 
• Lost to follow-up 
• Physician decision 
• Protocol deviation 
• Study terminated by Sponsor 
• Withdrawal by participant (only for discontinuing study drug, but will remain in 
study) 
The reason for participant discontinuation from study drug will be recorded in the eCRF. 
 
7.2. Early Termination Visit (Active or Follow-Up Period) 
If a participant is removed from the study or declines further participation during the study 
Active Period, the Early Termination (ET) visit should be the next visit completed as shown in 
the SoA per Cohort Assignment. Participants will enter the follow-up period to be monitored 
for safety and immunogenicity even if they discontinue study drug prematurely unless they 
withdraw consent. 
If a subject withdraws from the study after entering the follow-up period (i.e., after completed 
their Active Phase participation) the subject will be called for final assessments, per the End of 
Study Visit assessments as outlined in the SoA (0). 
 
7.3. Participant Withdrawal from the Study 
Participants have the right to withdraw from the study at any time and for any reason without 
prejudice to their future medical care by the Investigator or at the institution. A participant may 
withdraw from the study for reasons including but not limited to: 
• Death 
• Withdrawal by participant 
• Lost to follow-up 
• Study terminated by Sponsor 
The reason for participant withdrawal from the study will be recorded in the eCRF. 
At the time of withdrawal from the study, the ET visit should be completed, as shown in the SoA 
(Table 2). 
If the participant withdraws consent for disclosure of future information, the Sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. 
If a participant withdraws from the study, he/she may submit a written request of destruction 

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of any samples taken and not tested, and the investigator must document this in the site study 
records. 
 
7.4. Lost to Follow-Up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study. Consultation with the Sponsor is required if the new 
visit date is more than 7 days during each Cohort’s Active Period.  
• Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record. 
• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 

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8. 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and their timing are summarized in the SoA (Table 2). Protocol 
waivers or exemptions are not allowed. 
• Immediate safety concerns should be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or 
discontinue study intervention. 
• Adherence to the study design requirements, including those specified in the SoA is 
essential and required for study conduct. 
• All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log 
to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable. 
• Participants who experience any serious or severe AEs or any event of concern 
should be instructed to contact the study site and be scheduled for a visit for further 
evaluation. If an unscheduled visit occurs, the reason for the visit and data collected 
during the visit should be recorded and entered into the unscheduled eCRF. 
 
8.1. Immunogenicity Assessments 
Immunogenicity will be evaluated using cellular and humoral immune function assays from 
blood and mucosal (saliva and nasal swab) samples. Samples will be collected from all 
participants according to the time points specified in the SoA. The following analytes will be 
measured: 
Key Immunogenicity assessments: 
• VP1 specific IgA ASC by ELISpot 
• HBGA blocking antibodies by BT50 
• VP1 specific serum IgG MSD assay Exploratory Immunogenicity 
assessments: 
• VP1 specific IgG ASC 
• VP1 specific serum IgA 
• Ad5 neutralizing antibodies 
• VP1 specific IgG and IgA memory B cells 
• B cell immunophenotyping 
• Saliva VP1 IgA 
• Nasal VP1 IgA 
Additional exploratory immunogenicity assays may also be performed to further evaluate the 
activity of the VXA-G1.1-NN vaccine candidate. Note that not all sample timepoints may be 
relevant for some of the analysis, so not all assays may be performed at all timepoints. 
Sample collection, processing and shipping details are provided within the General and 
Immunogenicity Laboratory Manuals. 

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8.2.  Safety Assessments 
The safety of the VXA-G1.1-NN will be evaluated through the reporting of solicited symptoms 
of reactogenicity for 1 week following each study drug dose, unsolicited AEs for 4 weeks 
following each study drug dose, SAEs (including AESIs and NOCIs) for 6 months following the 
last study drug dose. The occurrence of these events should be reported to the Sponsor in an 
expedited manner, similarly to SAEs as described in Table 9. AESIs are listed in Appendix 5 
(Section 10.5). 
Planned time points for all safety assessments are provided in the SoA (Table 2). 
 
8.2.1 Physical Examination 
A complete physical examination will include, at a minimum, assessments of the skin, 
cardiovascular system, respiratory system, abdomen (gastrointestinal, liver and spleen) and 
neurological system. Height and weight will also be measured and recorded at Screening. 
A targeted, symptom-directed physical examination will include, at a minimum, assessments of 
the skin, respiratory system, cardiovascular system, and abdomen (liver and spleen) will be 
measured at site visits as specified in the SoA. 
 
8.3 Vital Signs 
Blood pressure, oral temperature, heart rate, and respiratory rate will be measured after the 
participant has been resting for 5 minutes. Vital signs will be measured prior to any blood 
draw that occurs at the same timepoint. 
 
8.3.1.  Clinical Safety Laboratory Assessments 
• See Appendix 2 (Section 10.2) for the list of clinical laboratory tests to be performed 
and the SoA for the timing and frequency. 
• The investigator must review the laboratory report, document this review, and record 
any clinically relevant changes occurring during the study in the AE section of the 
eCRF. The laboratory reports must be filed with the source documents. 
• All laboratory tests with values considered clinically significant during participation 
in the study or within 14 days after the last dose of study drug should be repeated 
until the values return to normal or baseline or are no longer considered clinically 
significant by the Investigator or Sponsor’s Medical Monitor (or designee). If such 
values do not return to normal/baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified, and the Sponsor notified. 
• Laboratory values which are abnormal AND lead to either the requirement for an 
intervention, the requirement for additional medications, or are felt to otherwise be 
medically important should be recorded as adverse events in the eCRF. 
• Hematology or serum chemistry parameters will be graded according to the FDA 
toxicity grading scale (Section 10.3.1.1.2) and will be adjusted according to local 
laboratory reference ranges. Participants have the ability to rescreen once should 
screening values fall outside of the allowed eligibility criteria, per the discretion of 
the Investigator. 
 

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8.4.  Adverse Events and Serious Adverse Events 
The definitions of any AE (solicited and unsolicited), SAE and AESIs/NOCIs can be 
found in Appendix 3 (Section 10.3). 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of any AE (solicited and unsolicited), or SAE.  
Investigators remain responsible for following up AEs, SAEs and other reportable safety events 
for outcome. 
 
8.4.1.  Time Period and Frequency for Collecting AE, SAE and Other Reportable Safety 
Event Information 
All AEs (solicited and unsolicited), SAEs and other reportable safety events that occur after the 
consent form is signed but before study administration must be reported by the investigator if 
the event cause the participant to be excluded from the study or is the result of a protocol-
specified intervention, including but not limited to washout or discontinuation of usual therapy, 
diet, or a procedure. 
 
Table 5 below summarizes the different reporting timelines for AEs (unsolicited and 
solicited), SAEs, SUSAR and pregnancy. 
Medical occurrences that begin before the start of study drug but after obtaining informed 
consent will be recorded on the Medical History/Current Medical Conditions section of the 
eCRF not the AE section. 
All SAEs will be recorded and reported to the Sponsor or designee immediately and under no 
circumstance should this exceed 24 hours, as indicated in Appendix 3 (Table 17). The 
investigator will submit any updated SAE data to the Sponsor within 24 hours of it being 
available. 

 
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Table 5 
Adverse Event Reporting Timelines to the Sponsor 
 
Type of Event 
AE (unsolicited) 
AE (solicited) 
SAE / AESI / NOCI 
Pregnancy 
Reporting period 
From first dose until 4 
weeks after last dose of 
study drug 
1 week after each 
study drug 
administration 
From first dose until end of 
Follow-Up Period/ EOS 
From first dose until end of 
Follow-Up Period/ EOS 
Reporting 
Timelines to the 
Sponsor 
Entered into the clinical 
database on an ongoing 
basis 
Entered into the 
clinical database on an 
ongoing basis 
Within 24 hours 
Within 24 hours 
Reporting 
Method 
AE eCRF 
Solicited Symptom 
Diary 
AE eCRF or SAER 
Form 
Pregnancy form 
AE, Adverse event; SAE, Serious adverse event; SUSAR, serious unexpected suspected adverse reaction.

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8.4.2. Method of Detecting AEs and SAEs  
Appendix 3 (Section 10.3) provides the method of recording (Table 10), evaluating 
severity (Table 11), and assessing causality (Table 16) of AEs and SAEs and the 
procedures for completing and transmitting SAE reports (Table 17). 
Care will be taken not to introduce bias when detecting AEs or SAEs. Open-ended and non-
leading questioning of participants is the preferred method to inquire for AE occurrences. 
 
8.4.3. Follow-Up of AEs and SAEs 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and evaluations as medically indicated to elucidate the nature and causality of the 
AE or SAE as fully as possible. This may include laboratory tests or investigations, 
histopathological examinations, or consultation with other health care professionals. 
The investigator will submit updated SAE data to Sponsor within 24 hours of receipt of the 
information. AEs and pregnancy will be followed by the investigator as specified in Appendix 4. 
 
8.4.4.  Regulatory Reporting Requirements for SAEs 
• Prompt notification by the investigator to the Sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of 
the study drug under clinical investigation are met. 
• The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of the study drug under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, Institutional Review Boards (IRB) and investigators. 
• Investigator safety reports must be prepared for SUSAR according to local regulatory 
requirements and Sponsor policy and forwarded to investigators as necessary. 
• An investigator who receives an investigator safety report describing a SAE or other 
specific safety information (e.g., summary or listing of SAEs) from the Sponsor will 
review and then file it along with the IB and will notify the IRB, if appropriate, according 
to local requirements. 
 
8.4.5.  Death Events 
Events resulting in death will be an SAE regardless of association to study drug. Death is an 
outcome and should not be reported as an event term. The event that leads to the death should be 
reported as the SAE term. 
 
8.4.6.  Pregnancy 
• Details of all pregnancies in female partners of male participants will be collected as 
outlined in Appendix 4 (Section 10.4). 
• If a pregnancy is reported, the investigator should inform the Sponsor within 24 hours 
of learning of the pregnancy and should follow the procedures outlined in Appendix 4 
(Section 10.4.3). 

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9. 
STATISTICAL CONSIDERATIONS 
 
9.1. 
Sample Size Determination 
The sample size was determined based on experience of a typical Phase 1 vaccine study, 
therefore there are no sample size calculations utilized for this study. Thirty subjects (30) will be 
enrolled in each cohort arm for a total planned enrollment of 30 subjects. The numbers of 
participants per scheduling group are predicted to yield meaningful safety and immunogenicity 
results in order to plan for future clinical trials. 
In previous human studies with Ad5 vectored oral tableted vaccines using the same vaccine 
platform (Ad5 vectored vaccine coding for target virus-specific antigens and dsDNA adjuvant), 
the vaccine was well tolerated at total doses up to 2x1011 IU. 
In this study we will observe the difference in IgA ASC responses of VXA-G1.1-NN given at 
multiple scheduled timepoints. In a prior Phase 1 study, for VXA-GI.1- NN at a dose of 1011 IU 
(N=23), the average IgA ASC count was 560 per 106 PBMCs with a standard deviation (SD) of 
740. Under the current protocol, immune responses with the initial vaccination at Day 1 versus 
with the second vaccination at will also be evaluated at each dose level in comparison to the 
multiple dosing schedules for the boost vaccination. 
Populations for Analyses 
 
Analysis Population 
Description 
Screened 
All subjects who enter screening (assigned a screening number) 
Dose 1 evaluable 
immunogenicity 
All enrolled participants who receive the study intervention to which they are 
assigned at the first dose, have at least 1 valid and determinate 
immunogenicity result after Dose 1, have blood collection within an 
appropriate window after Dose 1, and have no other important protocol 
deviations. 
Dose 2 evaluable 
immunogenicity 
All enrolled participants who receive 2 doses of the study intervention to 
which they are assigned, within the predefined window, have at least 1 valid 
and determinate immunogenicity result after Dose 2, have blood collection 
within an appropriate window after Dose 2, and have no other important 
protocol deviations. 
Dose 1 all-available 
immunogenicity 
All enrolled participants who receive at least 1 dose of the study intervention 
with at least 1 valid and determinate immunogenicity result after Dose 2. 
Safety 
All enrolled participants who receive at least 1 dose of the study drug. 
 
9.2. 
Statistical Analyses 
The statistical analysis plan (SAP) will be developed and finalized before database lock for any 
of the planned analyses. It will describe the participant populations to be included in the analyses 
and the procedures for accounting for missing, unused, and spurious data. This section provides a 
summary of the planned statistical analyses of the primary, secondary, and tertiary/exploratory 
endpoints. 

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9.2.1. Safety Analysis 
Safety will be summarized for each cohort:  
Cohort 1: (4-week boost vaccination) 10 subjects will receive two doses of 1x1010 IU± 0.5 log at 
Day 1 and Week 4 
Cohort 2: (8-week boost vaccination) 10 subjects will receive two doses of 1x1010 IU± 0.5 log at 
Day 1 and Week 8 
Cohort 3: (12-week boost vaccination) 10 subjects will receive two doses of 1x1010 IU± 0.5 log 
at Day 1 and Week 12 
 
Solicited symptoms of reactogenicity, unsolicited AEs, SAEs, clinical laboratory (blood 
chemistry, hematology, and urinalysis) test results, physical examination, and vital signs  will 
be summarized descriptively by study visit. 
All analyses will be performed separately for each cohort. 
 
Endpoint 
Statistical Analysis Methods 
Primary 
(measured from 
Day 1 through 
end of Active 
Period) 
VP1 specific IgA ASC by enzyme-linked  immunospot (ELISpot) 
Norovirus G1.1 histo-blood group antigen (HBGA) blocking antibodies (BT50) 
VP1 specific serum IgG by Mesoscale Discovery (MSD) assay 
Descriptive statistics will be provided for each reactogenicity endpoint for each dose 
and treatment group. Local reactions and systemic events from Day 1 through Day 8 
after each dose will be presented by severity and cumulatively across severity levels. 
Descriptive summary statistics will include counts and percentages of participants 
with the indicated endpoint. 
 Secondary 
(measured from 
Day 1 through 
end of Active 
Period) 
Frequency, duration, and severity of solicited symptoms of reactogenicity 
(local, systemic) for 1 week following  each dose of study drug 
Frequency, duration, and severity of unsolicited adverse events (AEs) and serious 
AEs (SAEs) through  each Study Period (4 weeks post each vaccination) 
AEs will be categorized according to the Medical Dictionary for Regulatory 
Activities (MedDRA) terms. Descriptive summary statistics (counts and 
percentages) will be provided for any AEs for each vaccine group. SAEs will be 
categorized according to MedDRA terms. The safety analyses are based on the 
safety population. Participants will be summarized by cohort. Missing 
reactogenicity diary data will not be imputed; missing AE dates will be handled 
according to the rules determined in the SAP. 
 Exploratory 
 
Occurrence of clinically significant abnormalities in laboratory parameters 
(chemistry, hematology and urinalysis) at 1 week after each study drug dose and in 
vital  signs immediately following each dose. 
Frequency, duration, and severity of all SAEs, AESIs and NOCIs through 6 months 
after last vaccination. 
Descriptive statistics will be provided for abnormal hematology and chemistry 
laboratory values at each time point as appropriate for each cohort, including 
grading shifts in hematology and chemistry laboratory assessments between 
baseline and each subsequent measurement. Descriptive summary statistics will 
include counts and percentages of participants with the indicated endpoint. 

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9.2.2. Immunogenicity Analysis 
Immunogenicity will be summarized according to the treatment group to which the subject was 
assigned. 
Immunogenicity samples will be drawn for all participants. Immunogenicity analyses will be 
based upon results from appropriately sized subsets of samples, according to the purpose. The 
statistical analysis of immunogenicity results will be primarily based on the evaluable 
immunogenicity populations. An additional analysis will be performed based on the all-available 
populations if there is a large enough difference in sample size between the all-available 
immunogenicity population and the evaluable immunogenicity population. 
Immunogenicity will be summarized for each cohort: 
Cohort 1: (4-week boost vaccination) 10 subjects will receive two doses of 1x1010 IU± 0.5 log at 
Day 1 and Week 4 
Cohort 2: (8-week boost vaccination) 10 subjects will receive two doses of 1x1010 IU± 0.5 log at 
Day 1 and Week 8 
Cohort 3: (12-week boost vaccination) 10 subjects will receive two doses of 1x1010 IU± 0.5 log 
at Day 1 and Week 12 
 
Endpoint 
Statistical Analysis Methods 
Exploratory 
(Key 
Immunogenicity 
Endpoints) 
VP1 specific IgG ASC 
VP1 specific serum IgA 
Ad5 neutralizing antibodies 
VP1 specific IgG and IgA memory B cells 
B cell immunophenotyping 
Saliva VP1 IgA 
Nasal Swab VP1 IgA 
All measures will be summarized descriptively for each cohort, for all 
timepoints where measured. The Dose 1 and Dose 2 evaluable 
immunogenicity populations will be used for these analyses. 
 
 
 

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9.3. 
Safety Oversight 
9.3.1. 
Internal Sponsor Review 
Safety data will be monitored on an ongoing basis by the investigator (or medically qualified 
designee) and the Sponsor’s Medical Monitor (or designee) in order to promptly identify and flag 
any event that potentially raises concern regarding a participant’s safety. 
The Medical Monitor will be a physician experienced in the conduct of research clinical studies 
whose primary responsibility will be to monitor participant safety. The Medical Monitor will be 
responsible for reviewing the cumulative safety data, including a review of safety laboratory 
test results and adverse event reporting. The Medical Monitor will be become and familiar with 
study-specific data as well as relevant background information about the disease, 
investigational drug, and target population under study. The Medical Monitor(s) will be 
empowered to request a safety review which can suspend the study, recommend amendments to 
the protocol, and/or to request further information. 
 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
• This study will be conducted in accordance with the protocol and with the following: 
Consensus ethical principles derived from international guidelines including the Declaration of 
Helsinki and Council for International Organizations of Medical Sciences (CIOMS) International 
Ethical Guidelines 
Applicable ICH Good Clinical Practice (GCP) Guidelines 
Applicable laws and regulations 
• The protocol, protocol amendments, ICF, Investigator Brochure, and other relevant 
documents (e.g., advertisements) must be submitted to an IRB/IEC by the investigator 
and reviewed and approved by the IRB/IEC before the study is initiated. 
• Any amendments to the protocol will require IRB/IEC approval before 
implementation of changes made to the study design, except for changes necessary to 
eliminate an immediate hazard to study participants. 
• Protocols and any substantial amendments to the protocol will require health 
authority approval prior to initiation except for changes necessary to eliminate an 
immediate hazard to study participants. 
• The investigator will be responsible for the following: 
Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by the 
IRB/IEC. 
Notifying the IRB/IEC of SAEs or other significant safety findings as required by IRB/IEC 
procedures. 

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Providing oversight of the conduct of the study at the site and adherence to requirements of 21 
CFR, ICH guidelines, the IRB/IEC, European regulation 536/2014 for clinical studies (if 
applicable), European Medical Device Regulation 2017/745 for clinical device research (if 
applicable), and all other applicable local regulations 
 
10.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the Sponsor with sufficient, accurate financial 
information as requested to allow the Sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 
 
10.1.3. 
Informed Consent Process 
• The investigator or his/her representative will explain the nature of the study to the 
participant and answer all questions regarding the study. 
• Participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 
CFR 50, local regulations, ICH guidelines, Health Insurance Portability and 
Accountability Act (HIPAA) requirements, where applicable, and the IRB/IEC or 
study center. 
• The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF. 
• Participants must be re-consented to the most current version of the ICF(s) during 
their participation in the study. 
• A copy of the ICF(s) must be provided to the participant. 
A participant who is rescreened is not required to sign another ICF if the rescreening occurs 
within 30 days from the previous ICF signature date. 
 
10.1.4. 
Exclusion of Women, Minorities, and Children (Special Populations) 
This clinical study will include women and men who are 18-55 years of age, inclusive, and 
volunteers of all races and ethnicities who meet the inclusion/exclusion criteria, regardless of 
religion, sex, or ethnic background. 
 
10.1.5. 
Data Protection 
• Participants will be assigned a unique identifier by the Sponsor. Any participant 
records or datasets that are transferred to the Sponsor will contain the identifier 
only; participant names or any information which would make the participant 
identifiable will not be transferred. 
• The participant must be informed that his/her personal study-related data will be used 
by the Sponsor in accordance with local data protection law. The level of disclosure 
must also be explained to the participant who will be required to give consent for 
their data to be used as described in the informed consent. 

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• The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
Sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
10.1.6. 
Dissemination of Clinical Study Data 
A clinical study report will be developed by the Sponsor at completion of data analysis. This 
report will be an integrated clinical and statistical report prepared according to the ICH E3 
guidelines. 
Sponsor will register the study and post study results regardless of outcome on a publicly 
accessible website in accordance with the applicable laws and regulations. 
10.1.7. 
Data Quality Assurance 
All participant data relating to the study will be recorded on printed or eCRFs unless transmitted 
to the Sponsor or designee electronically (e.g., laboratory data). The Investigator is responsible 
for verifying that data entries are accurate and correct by physically or electronically signing the 
eCRF. 
The Investigator must maintain attributable, legible, contemporaneous, original, accurate, and 
complete documentation (source data) that supports the information entered in the eCRF. 
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
Details describing monitoring strategy (e.g., risk-based initiatives in operations and quality such 
as risk management and mitigation strategies and analytical risk-based monitoring), methods, 
responsibilities and requirements, including handling of noncompliance issues and monitoring 
techniques (central, remote, or on-site monitoring) are provided in the Monitoring Plan. 
The Sponsor or designee is responsible for the data management of this study including quality 
review of the data. 
The Sponsor maintains ultimate responsibility for the quality and integrity of study data, even if 
study-related duties and functions are transferred to other individuals or organizations (e.g., 
contractors or contract research organizations). 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF by authorized site personnel are attributable, legible, contemporaneous, original, 
accurate, and complete from source documents; that the safety and rights of participants are 
being protected; and that the study is being conducted in accordance with the currently approved 
protocol and any other study agreements, ICH GCP, and applicable regulatory requirements. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the Investigator per ICH-GCP and local regulations or institutional policies. No 
records may be destroyed during the retention period without the written approval of the 
Sponsor. No records may be transferred to another location or party without written notification 
to the Sponsor. 
10.1.8. 
Source Documents 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents should be generated utilizing good 
documentation practices and are filed at the Investigator’s site. 

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Source documents are original documents, data, and records from which the participant’s eCRF 
data are obtained. These include but are not limited to hospital records, clinical and office charts, 
laboratory and pharmacy records, diaries, microfiches, radiographs, and correspondence. 
Data entered in the eCRF that are transcribed from source documents must be consistent with the 
source documents or the discrepancies must be explained. The Investigator may need to request 
previous medical records or transfer records, depending on the study. Also, current medical 
records must be available. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF. 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
10.1.9. 
Publication Policy 
The Sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the Sponsor will generally support 
publication of multicenter studies only in their entirety and not as individual site data. In this 
case, a coordinating investigator will be designated by mutual agreement. Requests for 
publication of site-specific data should be presented to the Sponsor for review and approval at 
least 90 days prior to submission for publication. 
10.2. 
Appendix 2: Safety Clinical Laboratory Tests 
• The tests detailed in Table 6 will be performed by the local laboratory, unless 
otherwise specified. 
• All safety laboratory samples including hematology, serum chemistry and serology 
are to be drawn by standard phlebotomy techniques, into the site prescribed 
appropriate tubes for the specific tests and amounts prescribed by local laboratory. 
Refer to the laboratory manual for further details on specimen collection and handling 
procedures. 
• Protocol-specific requirements for inclusion or exclusion of participant are detailed in 
Section 5. 
• Additional tests may be performed at any time during the study as determined 
necessary by the investigator or required by local regulations. 
• Investigators must document their review of each laboratory safety report. 
 
 
 
 
 
 

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Table 6 
Protocol-Required Safety Laboratory Assessments 
Hematology 
Hemoglobin, lymphocytes, hematocrit, neutrophils, eosinophils, platelet 
count, and complete white blood cell count 
Serum Chemistry 
Alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate 
aminotransferase (AST), total bilirubin, BUN, CPK, creatinine, random 
glucose, calcium, potassium, sodium, phosphorous, albumin, magnesium, 
amylase and total protein 
Urinalysis 
Protein, glucose ketones, bilirubin, urobilinogen, hemoglobin, pH, specific 
gravity, appearance, color, leukocyte esterase, nitrite 
Urine drug screen 
Amphetamines, methamphetamines, methadone, barbiturates, 
benzodiazepines, cocaine, opiates, methylenedioxymethamphetamine, 
phencyclidine, tetrahydrocannabinol 
Other laboratory 
assessments 
Hepatitis B surface antigen, hepatitis C virus antibody, and human 
immunodeficiency virus antibody types 1 and 2 (Screening only) 
Female participants of child-bearing potential: urine or serum pregnancy tests 
 

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10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-Up, and Reporting 
Table 7 
Definition of AE (Unsolicited and Solicited) 
 
AE Definition 
• 
An AE is any untoward medical occurrence in a clinical study participant, temporally associated 
with the use of study intervention, whether or not considered related to the study intervention, 
occurring after first dose of study drug. 
• 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use 
of study intervention. 
Definition of Unsolicited and Solicited AE 
• 
Unsolicited AEs are any AEs reported spontaneously by the participant, observed by the study 
personnel during study visits or those identified during review of medical records or source 
documents. Unsolicited AEs (all AEs not collected in the Solicited Symptom Diary during the 
first week following each study drug administration) will be monitored and collected from the 
time of each dose through 4 weeks post each dose.  
• 
Solicited AEs are predefined systemic signs and symptoms of reactogenicity for which the 
participant is specifically questioned, and which are noted by the participant in their Solicited 
Symptom Diary, including: 
 fever (any temperature 100°F or higher) 
 headache 
 myalgia (muscle pain) 
 abdominal pain 
 anorexia (defined and not eating) 
 nausea 
 vomiting 
 diarrhea 
 malaise/fatigue 
Participants will utilize a Solicited Symptom Diary issued on the day of each study drug 
administration to record solicited AE daily for the 1 week following each dose. 
 
 
 
 
 
 
 
 
 
 
 
 

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Table 8 
Events Meeting Definition of AE 
 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety 
assessments (e.g., vital signs measurements) that worsen from baseline and are considered 
clinically significant in the medical and scientific judgment of the investigator. 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study drug administration even though it may have 
been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected intervention- intervention interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention or a 
concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an 
intentional overdose taken with possible suicidal/self-harming intent. Such overdoses should be 
reported regardless of sequelae. 
Events NOT Meeting the AE Definition 
• 
Events that occurred from consent to pretreatment 
• 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that leads to the 
procedure is the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected at 
the start of the study that do not worsen. 
 

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Table 9 
Definition of SAE 
 
An SAE is defined as any serious adverse event that, at any dose: 
1. Results in death 
2. Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the participant was at 
risk of death at the time of the event. It does not refer to an event, which hypothetically might have 
caused death, if it were more severe. 
3. Requires inpatient hospitalization or prolongation of existing hospitalization 
• 
In general, hospitalization signifies that the participant has been admitted (usually involving at 
least an overnight stay) at the hospital or emergency ward for observation and/or treatment that 
would not have been appropriate in the physician’s office or outpatient setting. Complications 
that occur during hospitalization are AEs. If a complication prolongs hospitalization or fulfills 
any other serious criteria, the event is serious. When in doubt as to whether “hospitalization” 
occurred or was necessary, the AE should be considered serious. 
• 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE. 
4. Results in persistent or significant disability/incapacity 
An SAE is defined as any serious adverse event that, at any dose: 
• 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. 
• 
This definition is not intended to include experiences of relatively minor medical significance 
such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle) which may interfere with or prevent everyday life functions but do not 
constitute a substantial disruption. 
5. Is a congenital anomaly/birth defect 
6. Other situations: 
• 
Medical or scientific judgment should be exercised by the investigator in deciding whether SAE 
reporting is appropriate in other situations such as significant medical events that may jeopardize 
the participant or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These events should usually be considered serious. 
o Examples of such events include invasive or malignant cancers, intensive treatment for allergic 
bronchospasm, blood dyscrasias, convulsions or development of intervention dependency or 
intervention abuse. 
 
 
 
 
 
 
 
 
 

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Table 10   Definition of AESI and NOCI 
 
 
 
Table 11 
Recording of AE and/or SAE 
 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation 
(e.g., hospital progress notes, laboratory reports, and diagnostics reports) related to the event. 
• 
The investigator will then record all relevant AE/SAE/ information. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s medical records to 
the Sponsor in lieu of completion of the Sponsor required form. 
• 
There may be instances when copies of medical records for certain cases are requested by the 
Sponsor. In this case, all participant identifiers, with the exception of the participant number, will 
be redacted on the copies of the medical records before submission to the Sponsor. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, and/or 
other clinical information. Whenever possible, the diagnosis (not the individual signs/symptoms) 
will be documented as the AE/SAE. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
New Onset of Chronic Illness (NOCI) 
• 
A New Onset of Chronic Illness (NOCI) is defined as diagnosis post-enrollment and vaccination 
of a new medical condition which is chronic in nature, including those potentially controllable by 
medication (e.g. diabetes, asthma). 
Adverse Events of Special Interest (AESI) 
• 
A Significant Event of Special Interest (AESI) is not necessarily ordinarily considered to be a 
SAE, even though the event may be of clinical significance. They are events where Vaxart wishes 
to be promptly informed and to collect information relevant to the event. The same process used 
for reporting SAEs (see Section 8.4.4.  Regulatory Reporting Requirements for SAEs) 
should be followed. Adverse Events of Special Interest are listed within Appendix 5, Section 10.5. 

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Table 12 
Grading the Severity of AEs 
 
Assessment of Severity 
All AEs will be assessed by the investigator using a protocol-defined grading system. For events not 
included in the protocol-defined grading system, the following guidelines will be used to quantify 
severity: 
Mild: events require minimal or no treatment and do not interfere with the participant’s daily 
activities. 
Moderate: events result in a low level of inconvenience or concern with the therapeutic measures. 
Moderate events may cause some interference with functioning. 
Severe: events interrupt a participant’s usual daily activity and may require systemic drug therapy or 
other treatment. Severe events are usually incapacitating. 
Life threatening: any adverse drug experience that places the participant, in the view of the 
investigator, at immediate risk of death from the reaction as it occurred, i.e., it does not include a 
reaction that had it occurred in a more severe form, might have caused death. 
Changes in the severity of an AE should be documented to allow an assessment of the duration of the 
event at each level of intensity to be performed. Adverse events characterized as intermittent require 
documentation of onset and duration of each episode. 
 
Grading of Solicited Adverse Events 
Participants should be instructed to rate solicited symptoms of reactogenicity that are collected 
within their Solicited Symptom Diary based on the severity scale presented in Table 12. 
 
Table 13 
Grading of Solicited Symptoms of Reactogenicity 
 
Symptom 
Grading 
Normal 
0 
Mild 
Grade 1 
Moderate 
Grade 2 
Severe 
Grade 3 
Life Threatening 
Grade 4 
Fever 
(oral temp) 
< 100.4°F 
(< 38.0°C) 
100.4 – 101.1°F 
(38.0 – 38.4°C) 
101.2 – 102.0°F 
(38.5 – 38.9°C) 
102.1 – 104°F 
(39.0 – 40°C) 
> 104.0°F 
(>40°C) 
Headache 
None 
No interference with 
activity 
Repeated use of 
nonnarcotic pain 
reliever > 24 hours or 
some interference 
with activity 
Significant; any use of 
narcotic pain reliever 
or prevents daily 
activity 
ER visit or 
hospitalization 
Myalgia 
None 
Easily tolerated, 
causing minimal 
discomfort and does 
not interfere with 
everyday activitiesa 
Sufficiently 
discomforting to 
interfere with 
everyday activities 
Prevents normal 
everyday activities or 
requires medical 
advice 
ER visit or 
hospitalization 
Abdominal 
Pain 
None 
No interference 
with activity 
Some interference 
with activity not 
requiring medical 
intervention 
Prevents daily activity 
and requires medical 
intervention 
ER visit or 
hospitalization 
Anorexia 
None 
No interference 
with activity 
Some interference 
with activity not 
requiring medical 
intervention 
Prevents daily activity 
and requires medical 
intervention 
ER visit or 
hospitalization 

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Nausea/ 
Vomiting 
None 
No interference with 
activity or 1 to 2 
episodes/24 hours 
Some interference 
with activity or >2 
episodes/24 hours 
Prevents daily activity, 
requires outpatient IV 
hydration 
ER visit or 
hospitalization for 
hypotensive shock 
Diarrhea 
None 
2 to 3 loose stools or 
< 400 gms/24 hours 
4–5 stools or 400 
to 800 gms/24 hours 
6 or more watery stools 
or > 800gms/24 hours 
or requires outpatient 
IV hydration 
ER visit or 
hospitalization 
Malaise/ 
Fatigue 
None 
No interference with 
activity 
Some interference 
with activity 
Significant; prevents 
daily activity 
ER visit or 
hospitalization 
a Everyday activities include attendance at work, school and usual habits of the participants. 
 

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N
10.3.1.  Grading of Laboratory Abnormalities 
In accordance with the FDA’s Guidance on the toxicity grading scale for vaccine studies, new or 
worsening abnormalities in laboratory values for tests performed and listed in the guidance 
should be graded based on the severity scale presented in Table 13 (serum chemistry), Table 14 
(hematology) and Table 15 (urinalysis). 
 
Table 14 
Grading of Laboratory Abnormalities (Serum Chemistry) 
Seruma 
Mild 
(Grade 1) 
Moderate 
Severe 
(Grade 2) 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Sodium – Hyponatremia mEq/L 
132 to 134 
130 to 131 
125 to 129 
< 125 
Sodium – Hypernatremia mEq/L 
144 to 145 
146 to 147 
148 to 150 
> 150 
Potassium – Hyperkalemia mEq/L 
5.1 to 5.2 
5.3 to 5.4 
5.5 to 5.6 
> 5.6 
Potassium – Hypokalemia mEq/L 
3.5 to 3.6 
3.3 to 3.4 
3.1 to 3.2 
< 3.1 
Glucose – Hypoglycemia mg/dL 
65 to 69 
55 to 64 
45 to 54 
< 45 
Glucose – Hyperglycemia 
Insulin 
Fasting – mg/dL 
100 to 110 
111 to 125 
>125 
requirements or 
Random – mg/dL 
110 to 125 
126 to 200 
>200 
hyperosmolar coma 
BUN mg/dL 
23 to 26 
27 to 31 
> 31 
Requires dialysis 
Creatinine – mg/dL 
1.5 to 1.7 
1.8 to 2.0 
2.1 to 2.5 
> 2.5 or requires 
dialysis 
Calcium – hypocalcemia mg/dL 
8.0 to 8.4 
7.5 to 7.9 
7.0 to 7.4 
< 7.0 
Calcium – hypercalcemia mg/dL 
10.5 to 11.0 
11.1 to 11.5 
11.6 to 12.0 
> 12.0 
Magnesium – hypomagnesemia 
1.3 to 1.5 
1.1 to 1.2 
0.9 to 1.0 
< 0.9 
mg/dL 
Phosphorous – hypophosphatemia 
2.3 to 2.5 
2.0 to 2.2 
1.6 to 1.9 
< 1.6 
mg/dL 
CPK – mg/dL 
1.25 to 1.5 x ULN 
1.6 to 3.0 x ULN 
3.1 to 10 x ULN 
> 10 x ULN 
Albumin – Hypoalbuminemia g/dL 
2.8 to 3.1 
2.5 to 2.7 
< 2.5 
-- 
Total Protein – Hypoproteinemia 
5.5 to 6.0 
5.0 to 5.4 
< 5.0 
-- 
g/dL 
Alkaline phosphate – increase by 
1.1 to 2.0 x ULN 
2.1 to 3.0 x ULN 
3.1 to 10 x ULN 
> 10 x ULN 
factor 
Liver Function Tests – ALT, AST 
1.1 to 2.5 x ULN 
2.6 to 5.0 x ULN 
5.1 to 10 x ULN 
> 10 x ULN 
increase by factor 
Bilirubin – when accompanied by 
1.1 to 1.25 x ULN 
1.26 to1.5 x ULN 1.51 to 1.75 x UL 
> 1.75 x ULN 
any increase in Liver Function Test 
increase by factor 
Bilirubin – when Liver Function 
1.1 to 1.5 x ULN 
1.6 to 2.0 x 
2.0 to 3.0 x 
> 3.0 x ULN 
Test is normal; increase by factor 
ULN 
ULN 
Cholesterol 
201 – 210 
211 – 225 
> 226 
--- 
Pancreatic enzymes – amylase, 
1.1 to 1.5 x ULN 
1.6 to 2.0 x 
2.1 to 5.0 x 
> 5.0 x ULN 
lipase 
ULN 
ULN 
ULN = upper limit of normal 
a The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal parameters. 
Institutional normal reference ranges should be provided to demonstrate that they are appropriate. 
 

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Table 15 
Grading of Laboratory Abnormalities (Hematology) 
Hematologya 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Hemoglobin (Female), gm/dL 
11.0 to 12.0 
9.5 to 10.9 
8.0 to 9.4 
< 8.0 
Hemoglobin (Female) change 
Any decrease to 
1.6 to 2.0 
2.1 to 5.0 
> 5.0 
from baseline value, gm/dL 
1.5 
Hemoglobin (Male), gm/dL 
12.5 to 13.5 
10.5 to 12.4 
8.5 to 10.4 
< 8.5 
Hemoglobin (Male) change from 
Any decrease to 
1.6 to 2.0 
2.1 to 5.0 
> 5.0 
baseline value, gm/dL 
3 
WBC increase, cell/mm 
3 
WBC decrease, cell/mm 
3 
Lymphocytes decrease, cell/mm 
3 
Neutrophils decrease, cell/mm 
3 
Eosinophils, cell/mm 
3 
Platelets Decreased, cell/mm 
PT, increase by factor 
PTT, increase by factor 
Fibrinogen increase, mg/dL 
Fibrinogen decrease, mg/dL 
1.5 
10,800 to 15,000 
15,001 to 20,000 
20,001 to 
25,000 
> 25,000 
2,500 to 3,500 
1,500 to 2,499 
1,000 to 1,499 
< 1,000 
750 to 1,000 
500 to 749 
250 to 499 
< 250 
1,500 to 2,000 
1,000 to 1,499 
500 to 999 
< 500 
650 to 1500 
1501 to 5000 
> 5000 
Hypereosinophilic 
125,000 to 140,000 
100,000 to 
124,000 
25,000 to 
99,000 
< 25,000 
1.0 to 1.10 x ULN 
1.11 to 1.20 x 
ULN 
1.21 to 1.25 x 
ULN 
> 1.25 ULN 
1.0 to 1.2 x ULN 
1.21 to 1.4 x ULN 
1.41 to 1.5 x 
ULN 
> 1.5 x ULN 
400 to 500 
501 to 600 
> 600 
-- 
< 100 or 
150 to 200 
125 to 149 
100 to 124 
associated with 
gross bleeding 
or DIC 
DIC = disseminated intravascular coagulation; PT = prothrombin time; PTT = partial thromboplastin time; ULN = upper limit 
of normal; WBC = white blood cell 
a The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal parameters. 
Institutional normal reference ranges should be provided to demonstrate that they are appropriate. 
 
Table 16 
Grading of Laboratory Abnormalities (Urinalysis) 
Urine* 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life Threatening 
(Grade 4) 
Protein 
Trace 
1+ 
2+ 
Hospitalization or dialysis 
Glucose 
Trace 
1+ 
2+ 
Hospitalization for hyperglycemia 
Blood (microscopic), 
red blood cells per 
high power field 
1 to 10 
11 to 50 
> 50 and/or 
gross blood 
Hospitalization or packed red blood 
cells transfusion 
a The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal parameters. 
Institutional normal reference ranges should be provided to demonstrate that they are appropriate. 
 

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Table 17 
Assessment of Causality 
Assessment of Causality 
• 
For all solicited symptoms and unsolicited AEs and SAEs , the Investigator will make a judgment 
regarding the relationship of the AE to the study vaccine. All AEs must be recorded in the source 
documents as well as eCRF. 
• 
A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
• 
The investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as 
well as the temporal relationship of the event to study intervention administration will be 
considered and investigated. 
• 
The investigator will also consult the Investigator’s Brochure (IB) and/or Product Information, for 
marketed products, in his/her assessment. 
• 
For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred, and the investigator has minimal 
information to include in the initial report to the Sponsor. However, it is very important that the 
investigator always make an assessment of causality for every event before the initial transmission 
of the SAE data to the Sponsor. 
• 
The investigator may change his/her opinion of causality in light of follow-up information and 
send an SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
The relationship of the AE to study vaccine administration will be specified as follows: 
Not related: 
In the Investigator’s opinion, there is no causal relationship between study 
vaccine administration and the AE; 
Possibly Related: 
The AE follows a reasonable temporal sequence from the time of study 
vaccine administration but there may be another equally likely explanation for 
the event (e.g., the participant’s clinical state or other medications); 
Probably Related: 
The AE follows a reasonable temporal sequence from the time of study 
vaccine administration and cannot be reasonably explained by the known 
characteristics of the participant’s clinical state; 
Definitely Related: 
The AE follows a known temporal sequence from the time of study vaccine 
administration, cannot be explained by other disease or medications and the 
event is an objective and specific medical disorder or a recognized 
pharmacological phenomenon. 
 
 
 
 
 
 
 

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Table 18 
Reporting of SAEs 
SAE Reporting to Sponsor (or designee) via an Electronic Data Collection Tool 
• 
The primary mechanism for reporting an SAE to the Sponsor (or designee) will be the electronic 
data collection tool. 
• 
If the electronic system is unavailable, then the site will use the paper SAE data collection tool 
(see next section) to report the event within 24 hours. 
• 
The site will enter the SAE data into the electronic system as soon as it becomes available. 
• 
After the study is completed at a given site, the electronic data collection tool will be taken off- 
line to prevent the entry of new data or changes to existing data. 
• 
If a site receives a report of a new SAE from a study participant or receives updated data on a 
previously reported SAE after the electronic data collection tool has been taken off-line, then the 
site can report this information on a paper SAE form (see next section) or to the Medical Monitor 
by telephone. 
• 
Contacts for SAE reporting can be found in the Study Reference Manual (or equivalent). 

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10.4. 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information 
10.4.1. 
Definitions 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterilized (see below). 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study drug, additional evaluation should be considered. 
Women in the following categories are not considered WOCBP 
1. 
Premenarchal 
2. 
Premenopausal female with 1 of the following: 
• Documented hysterectomy 
• Documented bilateral salpingectomy 
• Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other than the above, (e.g., 
Mullerian agenesis, androgen insensitivity), investigator discretion should be applied to determining 
study entry eligibility. 
Note: Documentation can come from the site personnel’s review of the participant’s medical records, 
medical examination, or medical history interview. 
 
Postmenopausal female 
• A postmenopausal state is defined as no menses for 12 months without an alternative medical 
cause. 
Females on HRT and whose menopausal status is in doubt will be required to use one of the non-
estrogen hormonal highly effective contraception methods if they wish to continue their HRT during 
the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status 
before study enrollment. 

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10.4.2. 
Contraception Guidance 
Female Subjects 
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at 
least one of the following conditions applies: 
− Is not a woman of childbearing potential (WOCBP) 
OR 
− Is a WOCBP and using a contraceptive method that is highly effective (with a failure 
rate of < 1% per year), preferably with low user dependency (see table below), from 
consent through 60 days after the last dose of study drug, and agrees not to donate eggs 
(ova, oocytes) for the purpose of reproduction during this period. The investigator 
should evaluate the effectiveness of the contraceptive method in relationship to the 
first dose of study drug. 
− A WOCBP must have negative urine or serum pregnancy test (minimum sensitivity 25 
IU/L or equivalent units of human chorionic gonadotropin [HCG]) at extension 
enrollment visit before first administration of study drug in this study. 
Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. A reliable form of contraception must 
be approved by the Investigator (e.g., double barrier method, Depo-Provera, intrauterine device, 
Norplant, oral contraceptives, contraceptive patches). 
Male Subjects: 
Male participants are eligible to participate if they agree to the following from informed consent 
through 60 days after the last dose of study drug: 
• 
Refrain from donating sperm, except for the purpose of fertility analysis as part of 
this protocol 
PLUS: 
• 
Be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long term and persistent basis) and agree to remain abstinent 
OR 
• 
Must agree to use contraception/barrier (a male condom) 
10.4.3. 
Collection of Pregnancy Information 
Male participants with partners who become pregnant: 
• 
The investigator will attempt to collect pregnancy information on any male 
participant’s female partner who becomes pregnant while the male participant is in 
this study. 
• 
After obtaining the necessary signed ICF from the pregnant female partner directly, 
the investigator will record pregnancy information on the appropriate form and 
submit it to the Sponsor within 24 hours of learning of the partner’s pregnancy. The 
Sponsor will attempt to follow the female partner to determine the outcome of the 
pregnancy. Information on the status of the mother and child will be forwarded to the 
Sponsor. The Sponsor will follow the female partner until birth or termination of 

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pregnancy when possible. Any termination of the pregnancy will be reported 
regardless of fetal status (presence or absence of anomalies) or indication for the 
procedure. 
 
Female Subjects who become pregnant 
Any female participant who becomes pregnant while participating in the study will discontinue study 
drug or be withdrawn from the study. Additionally: 
• The investigator will collect pregnancy information, which will be recorded on the 
appropriate form and submitted to the Sponsor within 24 hours of learning of a participant's 
pregnancy. 
• The participant will be followed to determine the outcome of the pregnancy. The investigator 
will collect follow-up information on the participant and the neonate, and the information 
will be forwarded to the Sponsor. The participant will be followed until birth or termination 
of pregnancy. Any termination of pregnancy will be reported, regardless of fetal status 
(presence or absence of anomalies) or indication for the procedure. 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or SAE. A spontaneous 
abortion is always considered to be an SAE and will be reported as such. Any post-study 
pregnancy related SAE considered reasonably related to the study drug by the investigator 
will be reported to the Sponsor. While the investigator is not obligated to actively seek this 
information in former study participants, he or she may learn of an SAE through spontaneous 
reporting. 

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10.5. 
Appendix 5: Adverse Events of Special Interest (AESIs) 
 
The following adverse events (AEs) for potential immune-mediated medical conditions as well 
as events associated with thrombosis and thrombocytopenia are AEs of special interest (AESIs) 
and include new onset of chronic illness (NOCIs). These events should be monitored for actively 
throughout the entire study period and reported to the Sponsor in an expedited manner as 
outlined in Section 10.3. 
 
Gastrointestinal disorders: 
Liver disorders: 
• 
Celiac disease 
• 
Autoimmune cholangitis 
• 
Crohn’s disease 
• 
Autoimmune Hepatitis 
• 
Ulcerative colitis 
• 
Primary biliary cirrhosis 
• 
Ulcerative proctitis 
• 
Primary sclerosing cholangitis 
Metabolic diseases: 
• 
Addison’s disease 
• 
Diabetes mellitus type 1 
• 
Autoimmune thyroiditis (including 
Hashimoto thyroiditis) 
• 
Grave’s or Basedow’s disease 
Coagulopathy: 
 
• 
Acquired amegakaryocytic 
thrombocytopenia 
• 
Amegakaryocytic thrombocytopenia 
• 
Axillary vein thrombosis 
• 
Cavernous sinus thrombosis 
• 
Cerebral venous thrombosis 
• 
Deep vein thrombosis 
• 
Disseminated intravascular coagulation 
• 
Embolism venous 
• 
Hepatic vein thrombosis 
• 
Immune thrombocytopenia 
• 
Intracranial venous sinus thrombosis 
• 
Mesenteric vein thrombosis 
• 
Portal vein thrombosis 
• 
Pulmonary embolism 
• 
Pulmonary thrombosis 
• 
Pulmonary venous thrombosis 
• 
Severe fever with thrombocytopenia 
syndrome 
• 
Subclavian vein thrombosis 
• 
Thrombocytopenia 
• 
Thrombocytopenia purpura 
• 
Thrombotic thrombocytopenia purpura 
• 
Thrombosis 
• 
Transverse sinus thrombosis 
• 
Vena cava embolism 
• 
Vena cava thrombosis 
• 
Venous thrombosis 
Musculoskeletal disorders: 
• 
Antisynthetase syndrome 
• 
Polymyalgia rheumatic 
• 
Dermatomyosotis 
• 
Polymyositis 
• 
Juvenile chronic arthritis (including Still’s 
disease) 
• 
Psoriatic arthropathy 
• 
Mixed connective tissue disorder 
• 
Relapsing polychondritis 
• 
Scleroderma, including diffuse systemic 
form and CREST Syndrome 
• 
Rheumatoid arthritis 
• 
Systemic lupus erythematous 
• 
Systemic sclerosis 
• 
Spondyloarthritis, including ankylosing spondylitis, reactive arthritis (Reiter’s Syndrome) and 
undifferentiated spondyloarthritis. 
 

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Neuroinflammatory disorders: 
• 
Acute disseminated encephalomyelitis, including site specific variants (e.g., non-infections encephalitis, 
encephalomyelitis, myelitis, myeloradiculomyelitis) 
• 
Immune related peripheral neuropathies and plexopathies, including chronic inflammatory demyelinating 
polyneuropathy, multifocal motor neuropathy and polyneuropathies associated with monoclonal 
gammopathy 
• 
Cranial nerve disorders, including 
paralysis/paresis (e.g., Bell’s palsy) 
• 
Guillain-Barre syndrome, including Miller 
Fisher syndrome and other variants 
• 
Multiple sclerosis 
• 
Narcolepsy 
• 
Optic neuritis 
• 
Transverse Myelitis 
• 
Myasthenia gravis, including Eaton-Lambert syndrome 
Skin disorders: 
• 
Autoimmune bullous skin diseases 
(including pemphigus, pemphigoid and 
dermatitis herpetiformis 
• 
Rosacea 
• 
Alopecia aerate 
• 
Cutaneous lupus erythematosus 
• 
Erythema nodosum 
• 
Psoriasis 
• 
Morphoea 
• 
Sweet’s syndrome 
• 
Lichen planus 
• 
Vitiligo 

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Vasculitis: 
• 
Large vessels vasculitis including giant cell arteritis such as Takayasu’s arteritis and temporal arteritis 
• 
Medium sized/and or small vessels vasculitis including polyarthritis nodosa, Kawasaki’s disease, 
microscopic polyangiitis, Wegener’s granulomatosis, Churg-Strauss syndrome (allergic granulomatous 
angititis), Buerger’s disease thromboangitis obliterans), nerotizing vasculitis and anti-neutrophil 
cytoplasmic antibody (ANCA) positive vasculitis (type unspecified), Henoch-Schonlein purpura, Behcet’s 
syndrome, leulocytoclassic vasculitis 
Others: 
• 
Autoimmune glomerulonephritis (including IgA nephropathy, glomerulonephritis rapidly progressive, 
membranous glomerulonephritis, membranaoprolifative glomerulonephritis, and mesangioproliferative 
glomerulonephritis) 
• 
Antiphospholipid syndrome 
• 
Pernicious anemia 
• 
Autoimmune hemolytic anemia 
• 
Raynaud’ phenomenon 
• 
Autoimmune myocarditis/cardiomyopathy 
• 
Sarcoidosis 
• 
Autoimmune thrombocytopenia 
• 
Sjogren’s syndrome 
• 
Goodpasture syndrome 
• 
Stevens-Johnson Syndrome 
• 
Idiopathic pulmonary fibrosis 
• 
Uveitis 

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10.6. 
Appendix 6: Abbreviations 
 
Term 
Description 
Ad5 
Adenovirus type 5 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ANCA 
Anti-neutrophil cytoplasmic antibody 
ASC 
Antibody secreting cells 
BMI 
Body mass index 
CBER 
Center for Biologics Evaluation and Research – FDA 
CIOMS 
Council for International Organizations of Medical Sciences 
DP 
Drug product 
eCRF 
Electronic case report form 
ELISA 
Enzyme-linked immunosorbent assay 
ELISpot 
Enzyme-linked immunospot 
EOS 
End of Study 
ET 
Early Termination 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GI.1 
Norovirus genogroup I.1 
GII.4 
Norovirus genogroup II.4 
GMC 
Geometric mean concentration 
GMFR 
Geometric mean fold rise 
GMP 
Good Manufacturing Practice 
GMT 
Geometric mean titer 
HBGA 
Histo-blood group antigen 
HBsAg 
Hepatitis B surface antigen 
HCV 
Hepatitis C virus 
HDPE 
High-density polyethylene 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human immunodeficiency virus 
IB 
Investigator’s brochure 
ICF 
Informed Consent 
ICH 
International Council for Harmonisation 
SMC 
Safety Monitoring Committee 
IEC 
Independent Ethics Committee 

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IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G 
IND 
Investigational new drug 
IRB 
Institutional Review Board 
IU 
International units 
LS 
Least squares 
MedDRA 
Medical Dictionary for Regulatory Activities 
NOCI 
New Onset of Chronic Illness 
NoV 
Norovirus 
PBMC 
Peripheral blood mononuclear cells 
PF4 Antibody 
ELISA 
Platelet Factor 4 antibody ELISA 
PT/INR 
Prothrombin time and international normalized ratio 
RBD 
Receptor binding domain 
RCA 
Replication-competent Ad5 
RCC 
Radio-Controlled Capsules 
RNA 
Ribonucleic acid 
RT-PCR 
Reverse transcription polymerase chain reaction 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 
SoA 
Schedule of Activities 
SUSAR 
Serious unexpected suspected adverse reaction 
TLR3 
Toll-like receptor 3 
TTS 
Thrombolytic and thrombocytopenic syndrome 
VAAST 
Vector adjuvant antigen standard technology 
VP1 
Vaccine Protein 1, major capsid protein of norovirus 
WOCBP 
Women of childbearing potential 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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10.6  Appendix 7: Summary of Changes to Protocol 
 
 
PROTOCOL VXA-NVV-105 HISTORY: 
Document  
Date  
Protocol Amendment 1; Version 2.0  
25 August 2021 
Original Protocol; Version 1.0  
31 March 2021 
 
 
Overall Rationale for the Amendment:  
 
Per a request received from the FDA, Vaxart has amended this clinical protocol to incorporate 
information on the risk of  Thrombosis with Thrombocytopenia Syndrome (TTS) that has been observed 
with administration of two injected adenovirus-vectored COVID-19 vaccines being used under EUA. 
Enrollment under this protocol has completed, however subjects are currently in safety follow-up. All 
subjects will be reconsented with an updated informed consent form with updated risk information 
incorporating TTP at their next site visit. This requirement for updatd risk information has necessitated 
the modifications listed in the table below within protocol amendment 1 (Ver. 2.0). Additional minor 
changes incorporated into the amendment for added consistency/clarity are also summarized below. 
 
Section No. & Title 
Description of Change  
Brief Rationale 
Table 1.2: Schedule 
of Activities  
 
Table 1 has been updated to include 
allocation of an aliquot of serum collected at 
baseline to be stored for testing (e.g. PF4 
antibody ELISA) should an AESI related to 
blood clots be reported anytime during the 
study period. 
 
Per the direction of the FDA, a blood 
sample should be collected at baseline 
and stored for analysis should a 
participant experience a clotting adverse 
event. 
2.3 Benefit/ Risk 
Assessment 
The risk section has been updated to include 
language describing the adverse events 
reported with two injected adenovirus-
vectored vaccines (thromboembolism and/or 
thrombocytopenia), as well as with general 
information on how to monitor for and 
report the events should they occur in study 
participants. 
Because Vaxart’s VXA-G1.1-NN 
investigational vaccine utilizes an 
adenovirus vectored design, and per the 
director of the FDA, information on the 
risks of thromboembolism and /or 
thrombocytopenia have been added to 
Section 2.1 of the protocol. 
Appendix 5: 
Adverse Events of 
Special Interest 
(AESIs) 
The List of Adverse Events of Special 
Interest (AESIs) has been updated to include 
events to be monitored under the category of 
Coagulopathy 
Per the guidance received from FDA, 
the list of AEs of special interest (AESIs) 
has been updated to require sites to 
monitor study participants for the 
occurrence of TTS events. 
   
 
 
 

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Protocol Clarifications  
 
The following additional modifications have been incorporated within the current amendment to provide 
increased clarity and consistency: 
 
Section No. & Title 
Description of Change  
Inclusion Criteria #5 and 6.1. Appendix 
4: Contraceptive Guidance and 
Collection of Pregnancy Information 
Clarification added to inform that a pregnancy test should be 
conducted on all female participants and therefore the follicle-
stimulating hormone (FSH) testing will not be required. The 
women of childbearing potential category will no longer be utilized 
as a differential marker for pregnancy testing 
Inclusion Criteria #2 
Inclusion criterion #2 which refers to subjects “without significant 
medical” was revised to be worded consistent with exclusion 
criterion #1 which states subjects with “significant uncontrolled 
medical” should be excluded 
Section 1.1 Overall Design 
There was language present in error on page 8 of the original 
protocol which states that “absence of acute illness or new medical 
condition as confirmed by negative for SARS-CoV-2 if 
symptomatic”. SARS-CoV-2 negative testing is not a defining 
criterion for absence of acute illness or new medical condition and 
is not included elsewhere in the protocol. This erroneous language 
has been removed in the current amendment. 
Table 1.2: Schedule of Activities 
A serum or urine pregnancy test is acceptable prior to both the first 
and second vaccinations.  This has been clarified within the 
amendment. 
Section 8.3 Vital Signs 
Oral temperature will be collected as part of the Vital Sign 
procedures 
Table 1.2: Schedule of Activities 
For Day 57 vaccination day (Cohort 2) the super script has been 
corrected to “e” from “3”, which was in error. 
Table 1.2: Schedule of Activities 
Alcohol testing, required to evaluate the associated exclusion 
criteria, was included in the protocol however not listed out as a 
separate assessment within the Schedule of activities. It has been 
added there for consistency and added clarity. 
Exclusion Criteria #14 
Exclusion criterion #14 has been modified to clarify that subjects 
who test positive for THC use at screening will be allowed to 
participate in the trial if they commit to not using THC for the 
duration of the study, meet all other criteria and have a negative 
drug test at their Day 1 visit. 
Section 10.1.3 Informed Consent Process Language regarding the use of a second ICF has been deleted as a 
separate consent for future use is not applicable to this protocol. 
The current ICF form already addresses storage of samples for 
future use. 
 
 

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11. 
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