Single-ascending-dose Study of the Safety and Immunogenicity of NasoVAX
Phase: PHASE2
Conditions: Influenza
Sponsor: Altimmune, Inc.

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CLINICAL TRIAL 
PROTOCOL 
 
 
Study Title: 
Single-ascending-dose Study of the Safety and Immunogenicity of 
NasoVAX  
Study Number: 
ALT-103-201 
Study Phase: 
Phase 2a 
Test Product: 
Influenza vaccine, intranasal (NasoVAX) 
Indication: 
Prophylaxis of influenza 
Sponsor: 
Altimmune, Inc. 
19 Firstfield Road 
Gaithersburg, MD  20878  
USA 
 
 
Version 
Date 
Original Protocol (Version 1.0) 
17 March 2017 
Amendment 1 (Version 2.0) 
07 July 2017 
Amendment 2 (Version 3.0) 
31 July 2017 
Amendment 3 (Version 4.0) 
05 October 2017 
 
 
Confidentiality Statement 
The information in this document is confidential, and its contents are the property of 
Altimmune, Inc. and are confidential. Unauthorized copying, distribution, disclosure, or use is 
prohibited. 

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TABLE OF CONTENTS 
INVESTIGATOR SIGNATURE PAGE......................................................................................6 
LIST OF ABBREVIATIONS .......................................................................................................7 
1 
PROTOCOL SUMMARY ...................................................................................................9 
1.1 
Synopsis ............................................................................................................................9 
1.2 
Schedule of Events ..........................................................................................................14 
2 
INTRODUCTION...............................................................................................................15 
2.1 
Seasonal Influenza ..........................................................................................................15 
2.2 
Current Vaccines for Seasonal Influenza ........................................................................15 
2.3 
NasoVAX ........................................................................................................................16 
2.4 
Nonclinical Studies .........................................................................................................17 
2.5 
Previous Clinical Experience with Adenoviral Vectors .................................................18 
2.6 
Clinical Trials of NasoVAX ...........................................................................................18 
2.7 
Study Rationale ...............................................................................................................19 
2.8 
Benefit/Risk Assessment ................................................................................................19 
3 
STUDY OBJECTIVES AND ENDPOINTS .....................................................................20 
4 
STUDY DESIGN .................................................................................................................22 
4.1 
Overall Study Design ......................................................................................................22 
4.2 
Study Design Rationale ...................................................................................................23 
4.2.1 
Population ................................................................................................................23 
4.2.2 
Dose .........................................................................................................................23 
4.2.3 
Assessments .............................................................................................................24 
4.3 
Number of Sites and Subjects .........................................................................................24 
4.4 
Duration of Subject Participation and Study ..................................................................24 
5 
SUBJECT POPULATION .................................................................................................25 
5.1 
Inclusion Criteria ............................................................................................................25 
5.2 
Exclusion Criteria ...........................................................................................................26 
6 
INVESTIGATIONAL PRODUCTS .................................................................................28 
6.1 
Formulation, Packaging, and Administration .................................................................28 
6.1.1 
NasoVAX ................................................................................................................28 
6.1.2 
Placebo ....................................................................................................................29 
6.2 
Labelling .........................................................................................................................29 
6.3 
Storage ............................................................................................................................29 
6.4 
Blinding and Unblinding.................................................................................................29 
6.5 
Randomization and Timing of NasoVAX/Placebo.........................................................30 
6.6 
Stopping Criteria .............................................................................................................30 
6.7 
Accountability, Dispensing, and Destruction .................................................................30 
6.8 
Prior and Concomitant Treatments .................................................................................30 
6.8.1 
Prohibited Prior Medications and Vaccines ............................................................30 
6.8.2 
Prohibited Concomitant Medications and Vaccines ...............................................31 
6.9 
Contraception ..................................................................................................................31 

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6.10 Compliance .....................................................................................................................31 
7 
STUDY ASSESSMENTS AND DATA COLLECTION .................................................32 
7.1 
Demographics .................................................................................................................32 
7.2 
Medical History ..............................................................................................................32 
7.3 
Reactogenicity (Diary) ....................................................................................................32 
7.4 
Adverse Events (Including Medically Attended Events, Serious Adverse Events, and 
New-onset Chronic Illnesses) .........................................................................................32 
7.5 
Height and Weight ..........................................................................................................32 
7.6 
Complete Physical Examination .....................................................................................32 
7.7 
Targeted and Symptom-driven Physical Examination ...................................................33 
7.8 
Vital Signs .......................................................................................................................33 
7.9 
Electrocardiogram ...........................................................................................................33 
7.10 Blood Samples ................................................................................................................33 
7.10.1 Safety Laboratory Tests ...........................................................................................33 
7.10.2 Serum Samples (Immunogenicity) ..........................................................................34 
7.10.3 Peripheral Blood Mononuclear Cells (Immunogenicity) ........................................34 
7.11 Pregnancy Tests ..............................................................................................................34 
7.12 Nasopharyngeal Swabs ...................................................................................................34 
7.13 Viral Culture ...................................................................................................................34 
8 
STUDY VISITS ...................................................................................................................35 
8.1 
Screening (Within 28 Days Before Day 1) .....................................................................35 
8.2 
Dosing Period..................................................................................................................35 
8.2.1 
Day 1 .......................................................................................................................35 
8.2.2 
Day 2 (Telephone Contact) .....................................................................................36 
8.2.3 
Day 4 (± 1 Day) .......................................................................................................36 
8.2.4 
Day 8 (± 1 Day) .......................................................................................................37 
8.2.5 
Day 15 (± 1 Day) .....................................................................................................37 
8.2.6 
Day 29 (± 3 Days) ...................................................................................................37 
8.3 
Follow-up Period ............................................................................................................38 
8.3.1 
Day 91 (± 10 Days) .................................................................................................38 
8.3.2 
Day 181 (± 10 Days) ...............................................................................................38 
9 
ADVERSE EVENTS ..........................................................................................................39 
9.1 
Definitions.......................................................................................................................39 
9.1.1 
Adverse Event .........................................................................................................39 
9.1.2 
Medically Attended Adverse Event ........................................................................39 
9.1.3 
New-onset Chronic Illness ......................................................................................39 
9.1.4 
Serious Adverse Event ............................................................................................39 
9.2 
Reporting Responsibilities and Periods ..........................................................................40 
9.3 
Recording of Adverse Events .........................................................................................40 
9.4 
Assessment of Adverse Events .......................................................................................41 
9.4.1 
Severity ....................................................................................................................41 
9.4.2 
Relatedness (Causality) ...........................................................................................41 
9.5 
Clinical Laboratory, Physical Examination, Electrocardiogram and Vital Sign 
Abnormalities .................................................................................................................41 

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9.6 
Pregnancy ........................................................................................................................42 
9.7 
Reporting of Serious Adverse Events .............................................................................42 
9.8 
Follow-Up of Adverse Events ........................................................................................42 
10 
PREGNANCY .....................................................................................................................43 
11 
SUBJECT AND STUDY DISCONTINUATION .............................................................44 
11.1 Subject Withdrawal from the Study ................................................................................44 
11.2 Procedures for Subjects Who Terminate the Study Early ..............................................44 
11.3 Study Discontinuation .....................................................................................................44 
12 
STATISTICAL METHODS ..............................................................................................45 
12.1 Analysis Populations .......................................................................................................45 
12.2 Analysis Conventions .....................................................................................................45 
12.3 Subject Disposition .........................................................................................................45 
12.4 Demographic and Bassline Characteristics .....................................................................46 
12.5 Prior and Concomitant Medications ...............................................................................46 
12.6 Exposure .........................................................................................................................46 
12.7 Safety Analyses ...............................................................................................................46 
12.7.1 Primary Endpoints ...................................................................................................46 
12.7.2 Clinical Laboratory Tests and Vital Signs ..............................................................46 
12.7.3 Electrocardiograms ..................................................................................................47 
12.7.4 Shedding of Replication-deficient Vector ...............................................................47 
12.7.5 Laboratory-confirmed Adenovirus Infection ..........................................................47 
12.8 Immunogenicity Analyses ..............................................................................................47 
12.8.1 Secondary Endpoints (Humoral Immune Response) ..............................................47 
12.8.2 Exploratory Endpoints .............................................................................................48 
12.9 Sample Size and Power ...................................................................................................48 
12.10 Interim and Final Analyses .............................................................................................49 
13 
ETHICAL, LEGAL, AND ADMINISTRATIVE ISSUES ..............................................50 
13.1 Institutional Review Board Approval .............................................................................50 
13.2 Informed Consent............................................................................................................50 
13.3 Biological Samples .........................................................................................................50 
13.4 Confidentiality ................................................................................................................51 
13.5 Protocol Compliance .......................................................................................................51 
13.6 Protocol Amendments .....................................................................................................51 
13.7 Publication and Disclosure Policy ..................................................................................51 
13.8 Clinical Study Report ......................................................................................................51 
13.9 Financing and Insurance .................................................................................................51 
14 
STUDY DATA AND RECORDS ......................................................................................52 
14.1 Direct Access ..................................................................................................................52 
14.2 Source Documents ..........................................................................................................52 
14.3 Case Report Forms ..........................................................................................................52 
14.4 Study Monitoring ............................................................................................................52 
14.5 Data Management ...........................................................................................................52 
14.6 Retention of Records .......................................................................................................53 

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15 
REFERENCES ....................................................................................................................54 
16 
APPENDICES .....................................................................................................................55 
Appendix 1 
Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventive Vaccine Clinical Trials ..............................................................56 
Appendix 2 
Sample Subject Diary .....................................................................................59 
Appendix 3 
Immunosuppressive Medications ...................................................................65 
Appendix 4 
Protocol Amendments: Summary of Changes ...............................................66 
List of Tables 
Table 1 
NasoVax Study Design ..........................................................................................22 
 
List of Figures 
Figure 1 
Schematic Diagram of the Adenovirus Vector ......................................................28 
 

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INVESTIGATOR SIGNATURE PAGE 
 
ALT-103-201: Single-ascending-dose Study of the Safety and Immunogenicity of NasoVAX  
 
I have read the protocol and agree to conduct the trial in compliance with the International 
Council for Harmonisation Guideline for Good Clinical Practice and applicable regulatory 
requirements and to inform all who assist me in the conduct of this trial of their responsibilities 
and obligations. 
 
 
Signed: 
 
Date: 
 
 
 
 
Print Name: 
 
 

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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
Ad5 
adenovirus serotype 5 
AdVAV 
adenovirus serotype 5-vectored anthrax vaccine 
AE 
adverse event  
ALT 
alanine aminotransferase 
ANCOVA 
analysis of covariance 
AST 
aspartate aminotransferase 
CDC 
US Centers for Disease Control and Prevention 
CI 
confidence interval 
CSR 
Clinical Study Report 
DNA 
deoxyribonucleic acid 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
ELISA 
enzyme-linked immunosorbent assay 
ELISpot 
enzyme-linked immunosorbent spot assay 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
GMR 
geometric mean ratio 
GMT 
geometric mean titer 
HA 
hemagglutinin 
HAI 
hemagglutination inhibition 
HIV 
human immunodeficiency virus 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IgA 
immunoglobulin A 
IP 
investigational product 
IRB 
Institutional Review Board 
ITT 
intent-to-treat 
IUD 
intrauterine device 
LAIV 
live attenuated influenza vaccine 
MAE 
medically attended adverse event 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCI 
new-onset chronic illness 

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Abbreviation 
Definition 
NOAEL 
no-observed-adverse-effect level 
PBMC 
peripheral blood mononuclear cell 
PP 
per-protocol 
qPCR 
quantitative polymerase chain reaction 
RD 
replication deficient 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SCR 
seroconversion rate 
SD 
standard deviation 
SFU 
spot-forming unit 
SPR 
seroprotection rate 
SRC 
Safety Review Committee 
vp 
viral particles 
WT 
wild type 

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1 PROTOCOL SUMMARY 
1.1 
Synopsis 
Sponsor: Altimmune, Inc. 
Study Title: Single-ascending-dose Study of the Safety and Immunogenicity of NasoVAX  
Study Number: ALT-103-201 
Study Phase: 2a 
Study Objectives and Endpoints:  
OBJECTIVES 
ENDPOINTS 
Primary Objective 
• To describe the safety profile of 
NasoVAX in healthy adults when 
administered by intranasal spray at a 
single dose of 1×109, 1×1010, or 
1×1011 viral particles (vp)   
• Reactogenicity: counts and percentages of 
subjects with local events (nasal irritation, 
sneezing, nasal congestion, cough, sore throat, 
change in smell, change in taste, change in 
vision, eye pain) and systemic events (headache, 
fatigue, muscle ache, nausea, vomiting, diarrhea, 
chills, fever) for 14 days after vaccination 
• Adverse events (AEs): counts and percentages of 
subjects with AEs from Day 1 to Day 29; 
medically attended AEs (MAEs), serious AEs 
(SAEs), new-onset chronic illnesses (NCIs) from 
Day 1 to Day 181 
Secondary Objective 
• To evaluate the humoral immune 
response to NasoVAX when 
administered by intranasal spray at a 
single dose of 1×109, 1×1010, or 
1×1011 vp 
• Antibody level measured by hemagglutination 
inhibition (HAI) in serum: 
o Geometric mean titer (GMT): the antilog of 
the mean of the log-transformed titers 
o Geometric mean ratio (GMR): the ratio of 
postvaccination and prevaccination GMTs 
within the same dose group  
o Seroprotection rate (SPR): the percentage of 
subjects with a HAI titer ≥ 1:40 
o Seroconversion rate (SCR): the percentage of 
subjects with either a baseline HAI titer 
< 1:10 and a postvaccination titer ≥ 1:40 
(which is 4 times the assay lower limit of 
quantitation), or a baseline HAI titer ≥ 1:10 
and a 4-fold increase in postvaccination HAI 
titer relative to baseline 
• Antibody level measured by microneutralization 
in serum: 
o GMT  
o Responder rate: the proportion of subjects 
with 2-fold and 4-fold rise since baseline 

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Exploratory Objectives 
• To evaluate the cellular immune 
response to NasoVAX when 
administered by intranasal spray at a 
single dose of 1×109, 1×1010, or 
1×1011 vp 
• Spot-forming units (SFUs) to hemagglutinin 
(HA) peptides measured by enzyme-linked 
immunosorbent spot assay (ELISpot) in 
peripheral blood mononuclear cells (PBMCs): 
o Geometric mean SFUs 
o Responder rate 
• To evaluate the mucosal immune 
response NasoVAX when 
administered by intranasal spray at a 
single dose of 1×109, 1×1010, or 
1×1011 vp  
• Immunoglobulin A (IgA) antibody level 
measured by enzyme-linked immunosorbent 
assay (ELISA): 
o GMT  
o GMR 
• To evaluate the humoral immune 
response against nonrepresented 
influenza strains after NasoVAX 
administration 
• Humoral immune response to nonrepresented 
influenza strain antigens (antibody level 
measured by HAI and microneutralization in 
serum) against each strain tested:  
o GMT  
o GMR  
o Responder rate: the number and percentage 
of subjects with 2-fold and 4-fold rise since 
baseline 
• To evaluate the effect of predose Ad5 
serum antibody levels on the 
immunogenicity of NasoVAX 
• Predose Ad5 antibody GMT measured by 
microneutralization in serum 
• Day 29 GMR and responder rate from antibody 
level measured by HAI in serum 
• To compare immunogenicity results 
to those obtained from banked 
samples from a previous study of 
licensed seasonal vaccine in a similar 
subject population 
• Antibody level measured by HAI in serum: 
o GMT 
o GMR  
o SPR 
o SCR 
• Antibody level measured by microneutralization 
in serum: 
o GMT  
o Responder rate 
• SFUs to hemagglutinin peptides measured by 
ELISpot in PBMCs: 
o Geometric mean SFUs 
o Responder rate 
• IgA antibody level measured by ELISA: 
o GMT  
o GMR 

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Study Design: The Schedule of Events showing time points for all study procedures is provided 
in Section 1.2. 
This is a Phase 2a, randomized, double-blind, placebo-controlled trial to evaluate the safety and 
immunogenicity of NasoVAX in healthy adults 18 to 49 years of age. Subjects will be screened 
within 28 days of randomization (Day 1). Approximately 60 subjects who meet all inclusion and 
no exclusion criteria and provide written informed consent will be enrolled into 3 sequential 
cohorts of 20 subjects each defined by the viral particle dose (1×109, 1×1010, and 1×1011 vp). 
Within each cohort and its sentinel group, subjects will be randomized in a 3:1 ratio to receive 1 
intranasal dose of NasoVAX or placebo (Day 1).  
A sentinel cohort of 5 subjects from each cohort will be dosed. Dosing of the remainder of each 
cohort may proceed after the last sentinel subject completes Day 8 if no events meeting stopping 
criteria have occurred. The Safety Review Committee (SRC), consisting of the Investigator, the 
Medical Monitor, and a Sponsor Representative, will review all AE, reactogenicity, and 
laboratory data through at least Day 8 for all subjects in each cohort before subjects are 
randomized to the next higher dose. If any event meeting the following criteria occurs, the SRC 
will review all available safety information before additional patients are dosed: 
• Occurrence of any related SAE or Grade 4 AE 
• Occurrence of 2 Grade 3 AEs in the same organ system 
• Occurrence of the same Grade 3 laboratory abnormality in 2 or more subjects 
Each subject will record reactogenicity (local events, systemic events, and oral temperature) and 
whether any medication or treatment was used for the symptom(s) in a diary daily for 14 days 
after the NasoVAX/placebo dose. Each subject will be contacted by telephone on Day 2 for 
safety assessment and review of the diary. Subjects will return to the investigational site on Days 
4, 8, 15, 29, 91, and 181 for safety and immunogenicity assessments. At each visit, the subject 
will also be asked about the interim medical history and use of any medications. 
A serum sample will be collected from each subject for evaluation of influenza HAI assay 
against A/California/04/2009(H1N1) predose on Day 1 and on Days 4, 8, 15, 29, 91, and 181; 
adenovirus serotype 5 (Ad5) antibody, microneutralization assay against both 
A/California/04/2009(H1N1) and nonrepresented strains, and HAI against nonrepresented strains 
will also be evaluated at Days 1 and 29. A whole blood sample will be collected from each 
subject and processed to isolate PBMCs for evaluation of T-cell responses by ELISpot predose 
on Day 1 and on Day 8.  
A nasopharyngeal swab sample will be collected from each subject at Screening and on Days 4, 
8, 15, 29, and 91 to measure concentration of the Ad5 vector for assessment of vaccine vector 
shedding by quantitative polymerase chain reaction (qPCR) assay. Once a negative result is 
obtained, later samples may not be tested. ELISA for measurement of IgA will also be performed 
on the swab samples from Screening and Day 29 for evaluation of mucosal immune response. 
Banked samples from a previous study of licensed seasonal vaccine in a similar subject 
population will be analyzed alongside samples collected in this study. 
All AEs and medications will be recorded from signing of the informed consent form to Day 29. 
Thereafter to the end of the study, only MAEs, NCIs, SAEs, immunosuppressive medications, 
and vaccines will be recorded. Samples for clinical laboratory tests (hematology, serum 
chemistry, urinalysis) will be collected at Screening and on Days 8 and Day 29. A complete 
physical examination and vital signs will be performed at Screening and predose on Day 1, and 

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targeted and symptom-driven physical examinations will be performed and vital signs measured 
2 hours postdose and on Days 4, 8, 15, and 29. An electrocardiogram (ECG) will be performed at 
Screening and on Day 29. If a subject experiences acute symptoms compatible with adenoviral 
infection within 28 days after the NasoVAX/placebo dose, a sample will be collected for viral 
culture as clinically indicated.  
One interim analysis of humoral immunogenicity data and safety data (including summaries of 
AE, reactogenicity, concomitant medications and vaccines, vital signs, ECG, and laboratory data 
and listing of any viral culture results) will be conducted when all data through the Day 29 visit 
is available and monitored for all subjects. 
Duration of Subject Participation and Study: Each subject will participate in the study for 
approximately 7 months.  
The end of the study is defined as the last visit of the last subject participating in the study. The 
expected duration of the study is approximately 9 months. 
Study Centers: 1 site in the United States 
Number of Subjects Planned: 60 subjects 
Diagnosis and Main Eligibility Criteria: Healthy adults 18 to 49 years of age 
Test Product: NasoVAX (influenza vaccine, intranasal) administered by intranasal spray at a 
single dose of 1×109, 1×1010, or 1×1011 vp 
Reference Product: Normal saline administered by intranasal spray at a single dose 
Concomitant Products: None 
Statistical Methods:  
Sample Size and Power: The sample size for this study was selected as adequate and reasonable 
for an initial review of the safety and immunogenicity profile of the NasoVAX at doses to be 
well tolerated by young adults, rather than for statistical power. The sample size will permit 
initial estimates of reactogenicity. Given a total of 45 subjects receiving NasoVAX, the study 
will have an 80% probability of detecting at least 1 AE which occurs at a rate of 3.6%. If no 
SAEs are observed among the 45 subjects who receive NasoVAX, an approximation to the 
1-sided upper bound of the 90% confidence interval (CI) on the rate of SAE occurrence would be 
5%. 
Analyses: 
Safety  
The primary endpoint for evaluation of the safety profile is the number and percentage (95% CI) 
of subjects with solicited and unsolicited AEs recorded postvaccination. Safety analyses will be 
performed using the Safety Population. 
The number (percentage, 95% CI) of subjects with local reactions and systemic events will be 
summarized by dose group and overall. Reactogenicity events will also be summarized by 
severity.  
The number (percentage, 95% CI) of subjects with AEs from Day 1 to Day 29 (including MAEs, 
NCIs, SAEs) will be summarized for each MedDRA (Medical Dictionary for Regulatory 
Activities) system organ class and preferred term and by dose group and overall. The number 
(percentage) of subjects with MAEs, with NCIs, and with SAEs from Day 1 to Day 181 will be 
summarized in a similar fashion. The number (percentage, 95% CI) of subjects with AEs by 
severity and by relationship to investigational product (IP) will also be summarized.    

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Listings of AEs, MAEs, NCIs, and SAEs will be provided.  
Summary statistics for continuous parameters (clinical laboratory tests and vital signs) will be 
presented by dose group as follows: prevaccination, postvaccination, and change from 
prevaccination to postvaccination assessment. 
The number and percentage of subjects with postvaccination clinical laboratory values or vital 
sign values recorded as newly abnormal (ie, an event with an increase in the toxicity grade 
relative to the baseline value and with a severity grade of moderate or higher) after study 
vaccination will be tabulated. Shift tables which cross-tabulate the prevaccination and 
postvaccination clinical laboratory values of each subject by severity grade will be prepared.  
Summaries of the number and percentage of subjects with normal, abnormal not clinically 
significant, and abnormal clinically significant ECG interpretations will be presented. 
For shedding of the vector, data will be summarized by count and percent positive by time point, 
along with median copy number.   
Viral culture results for evaluation of adenovirus infection will be listed. 
Immunogenicity  
Immunology analyses will be conducted using the Intent-to-treat (ITT) and Per-protocol (PP) 
Populations with primary conclusions drawn from the PP Population. Analyses based on the ITT 
Population will be undertaken and presented only if >5% of subjects in any 1 dose group were 
excluded from the PP Population. No imputation for missing data will be performed. Data will 
be transformed as appropriate prior to analysis. 
Baseline is defined as the sample collected prior to IP administration on Day 1. 
The primary variable of interest for assessment of humoral immune response to the NasoVAX 
antigen is homologous HAI antibody titer. The following HAI immunogenicity measures and 
their 95% CIs will be summarized by dose group:   
• GMT at baseline and postvaccination on Days 4, 8, 15, 29, 91, and 181 
• GMR on Days 4, 8, 15, 29, 91, and 181 (analysis of GMR will be performed using analysis 
of covariance [ANCOVA] with baseline titer as a covariate) 
• SPR on Days 4, 8, 15, 29, 91, and 181 
• SCR on Days 4, 8, 15, 29, 91, and 181 
Humoral immune response as measured by microneutralization in serum will be summarized by 
GMT at baseline and postvaccination on Day 29 and responder rate (the proportion of subjects 
with 2-fold and 4-fold rise since baseline) (95% CI) on Day 29. 
Cellular responses (ELISpot SFUs to influenza HA peptides) will be summarized by geometric 
mean at baseline and postvaccination on Day 8 and responder rate on Day 8. 
Humoral immune response to nonrepresented influenza strain antigens (antibody level measured 
by HAI and microneutralization in serum) against each strain tested will be summarized by GMT 
at baseline and postvaccination on Day 29; GMR postvaccination on Day 29; and responder rate 
(the proportion of subjects with 2-fold and 4-fold rise since baseline) on Day 29. 
For the effect of predose Ad5 serum antibody levels on immunogenicity of NasoVAX on Day 
29, analysis will be performed using ANCOVA, with baseline Ad5 titer as a covariate. 
Immunogenicity results from samples collected in this study will be compared to those from 
banked samples from a previous study of licensed seasonal vaccine in a similar subject 
population using a 2-sample comparison of means or nonparametric tests as indicated. 
 

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1.2 
Schedule of Events 
Study Visit 
Screening 
Dosing Period 
Follow-up Period 
Day 1 
Day 2a 
Day 4 
Day 8 
Day 15 
Day 29 
Day 91 
Day 181 
Window (days) Day -28 to Day -1 Predose Postdose 
± 1 
± 1 
± 1 
± 3 
± 10 
± 10 
Informed consent 
X 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
Concomitant medication recording 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Immunosuppressive medication and 
vaccine recording 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
Eligibility criteria check 
X 
X 
 
 
Complete PE 
X 
X 
 
 
 
 
 
 
 
 
Targeted and symptom-driven PE 
 
 
Xb 
 
X 
X 
X 
X 
 
 
Height and weight 
X 
 
 
 
 
 
 
 
 
 
ECG 
X 
 
 
 
 
 
 
X 
 
 
Vital signsc 
X 
X 
Xb 
 
X 
X 
X 
X 
 
 
Drug and alcohol screen 
X 
X 
 
 
 
 
 
 
 
 
Laboratory samples: 
 
Hepatitis B and C and HIV tests 
X 
 
 
 
 
 
 
 
 
 
Safety laboratory tests 
X 
 
 
 
 
X 
 
X 
 
 
Serum (S)/urine (U) pregnancy testd 
S 
U 
 
 
 
 
 
U 
 
 
Serum sample for humoral response 
Xe 
 
X 
X 
X 
Xe 
X 
X 
Whole blood sample for isolation of 
PBMCs 
 
X 
 
 
 
X 
 
 
 
 
Nasopharyngeal swab   
X 
 
 
 
X 
X 
X 
X 
X 
 
AE (including MAEs, NCIs, and SAEs) 
assessment 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Randomization 
X 
 
 
 
NasoVAX/placebo administration 
X 
 
 
Viral culture 
 
If a subject experiences acute symptoms compatible with adenoviral infection 
within 28 days after dose, collect a sample as clinically indicated. 
 
 
Distribution (D)/review (R) of Diary  
D 
R 
R 
R 
R 
 
 
MAE/NCI/SAE assessment 
 
 
 
 
 
 
 
 
X 
X 
AE = adverse event; ECG = electrocardiogram; ET = early termination; HIV = human immunodeficiency virus; MAE = medically attended adverse event; NCI = new-onset chronic 
illness; PBMC = peripheral blood mononuclear cell; PE = physical examination; SAE = serious adverse event. 
a Telephone call  
b 2 hours postdose 
c Measured before any blood sample collection 
d Required for all women who are not surgically sterilized or have laboratory confirmation of postmenopausal status  
e A larger serum sample will be collected on Days 1 and 29 for additional assays (see Section 7.10.2 and the laboratory manual for details). 

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2 INTRODUCTION 
2.1 
Seasonal Influenza 
Influenza is one of the most common viral respiratory infections, leading to significant morbidity 
and mortality. In particular, individuals with chronic medical conditions or who are pregnant or 
at the extremes of age are vulnerable to developing influenza-related complications [CDC 2016]. 
The World Health Organization reports 3 to 5 million severe cases and between 250,000 and 
500,000 deaths annually [WHO 2016]. The number of deaths associated with seasonal influenza 
varies from year to year, depending on the severity of circulating strains and the effectiveness of 
that year’s influenza vaccine. 
Influenza illness is commonly associated with acute onset of fever, cough, sore throat, and nasal 
congestion and resolves within a week in most individuals but can be associated with severe 
respiratory distress, secondary pneumonia, and increased risk of myocardial infarction 
[CDC 2016; WHO 2016]. 
It is well established that elderly populations have greater influenza-related morbidity and 
mortality. The US Centers for Disease Control and Prevention (CDC) estimated that 90% of 
influenza-associated deaths between 1976 and 2007 occurred among adults 65 years and older 
[CDC 2010]. Even though usually less severe, the burden of influenza in healthy young adults is 
also significant with an average of 2.4 million outpatient visits and 32,000 hospitalizations in the 
US each year [Molinari 2007].   
Many influenza strains circulate during a given influenza season and the individual strains are 
systematically named by (1) the type of influenza virus (either A or B), (2) the geographical 
location where the strain was isolated, (3) which isolate from that location it represents (starting 
with the number 01), and (4) the year it was isolated. For example, the isolate termed 
A/California/04/2009 is the strain associated with the 2009 pandemic. This system of naming 
virus strains sometimes includes information on the subtype of influenza virus as a suffix at the 
end of the name, eg, A/California/04/2009(H1N1), where the familiar designation H1N1 reveals 
the subunit structure of the virus, designating an influenza subtype comprised of hemagglutinin 
(HA) protein H1 and neuraminidase protein N1.   
2.2 
Current Vaccines for Seasonal Influenza 
The CDC recommends that everyone in the United States over 6 months of age receive an annual 
influenza vaccination. Most currently licensed vaccines are based on circulating influenza strains 
adapted to grow in chicken eggs. The viruses are harvested, inactivated, and combined into 
trivalent (containing A H1N1, A H3N2, and B strains) or quadrivalent formulations (which also 
contain a second B strain) and administered by injection. Other injectable vaccines currently 
available include a tissue culture-derived vaccine (Afluria, Seqirus), a recombinant HA protein 
vaccine (Flublok, Protein Sciences), and an adjuvanted inactivated vaccine (Fluad, Seqirus). In 
general, these vaccines are well tolerated but provide limited protection to influenza viruses that 
are not well matched to the vaccine strains.  

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An intranasal live attenuated influenza vaccine (LAIV) has been licensed since 2003 (FluMist, 
MedImmune). This product is replication-competent, and its use is limited to older children and 
adults up to age 49 years because of safety concerns. LAIV does not elicit antibody responses at 
the levels of other licensed influenza vaccines, but initial studies showed significant cellular 
immune responses, and protective efficacy was demonstrated in Phase 3 studies. More recently 
postmarketing studies have shown declining effectiveness, and FluMist was not recommended 
for use in the 2016-2017 influenza season [Seasonal 2016]. Possible reasons for the decreased 
effectiveness seen may be instability in viral sequence or poor immunogenicity in the presence of 
pre-existing antibody. 
For all types of influenza vaccines, effectiveness can vary greatly from year to year, and in many 
years overall protection is poor. According to the CDC, the average overall adjusted vaccine 
effectiveness for influenza seasons has been approximately 40% from 2005 to 2015 [CDC 2016]. 
One reason for vaccine ineffectiveness is the constantly changing nature of influenza virus 
strains. The viral protein HA is an important target of vaccination, and each type of HA protein, 
such as H1 or H3, has multiple forms which can vary from year to year. Because the process 
used to produce over 99% of influenza vaccines today requires 6 months of advance planning, 
regulatory agencies must commit to the strains to be used well in advance of the start of the 
influenza season. The low estimated 19% overall efficacy of the 2014-2015 influenza vaccine in 
the United States was attributed to the fact that most of the H3N2 viruses circulating that season 
were of a different form than the H3N2 strain included in vaccine production 
[Zimmerman 2016]. Worse still, a more dramatic change in influenza virus makeup occasionally 
arises when an entirely new HA protein emerges, which can result in a human pandemic. 
Because humans have never encountered the new HA protein, they are likely to have little or no 
immunity, leaving them at much greater risk for serious complications or death.  
Changes in influenza virus formulation and manufacturing are essential to protect the public 
from the significant morbidity and mortality associated with seasonal influenza infections. The 
ability to provide cross-protection between different HA protein types is key to addressing the 
efficacy problems created by ever-mutating influenza viruses. Avoidance of egg-based 
production, because of supply chain risks, manufacturing timelines, and potential for allergic 
response in many individuals is another goal for new influenza vaccines. Altimmune, Inc. is 
developing NasoVAX, an Ad5-vectored, intranasal influenza vaccine, to address these issues.     
2.3 
NasoVAX  
Adenovirus is a naturally occurring respiratory virus that has been used frequently as a vector to 
introduce genetic material into cells. By incorporating the influenza HA gene into replication-
deficient (RD) adenovirus (Ad-HA) and applying the Ad-HA into the nose, the adenoviral vector 
can transduce the HA gene into cells of the nasal mucosa, leading to transient expression of the 
encoded HA protein. An immune response to the expressed HA antigen can thus be induced. 
Thus, RD Ad-HA constructs hold potential as a novel type of influenza virus vaccine that does 
not require administration by needle injection.  
NasoVAX is based on Altimmune’s RespirVec platform, an RD-Ad5 vector that expresses the 
protein of interest within respiratory epithelial cells. In the case of NasoVAX, the vector contains 
a genetic insert encoding the HA surface protein antigen from influenza type A or B. The 

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RespirVec platform has the potential to provide a more rapid production system than egg-based 
vaccines. In previous nonclinical and clinical studies, NasoVAX does not appear impeded by 
prior existing adenoviral immunity and generates strong antibody and cellular immune 
responses. In an animal challenge model, NasoVAX protected against highly divergent influenza 
strains and was protective within days of administration.   
2.4 
Nonclinical Studies 
The Sponsor has conducted nonclinical studies of immunogenicity, lethal challenge, 
biodistribution, and single-dose and repeat-dose toxicity with Ad5-vectored vaccines 
incorporating other influenza genetic inserts and with a similar Ad5-vectored vaccine AdVAV 
(Ad5-vectored anthrax vaccine). Additional details of the studies can be found in the current 
Investigator Brochure. 
Studies of humoral immunogenicity in mice and ferrets demonstrated that Ad5-vectored vaccines 
encoding an HA surface protein antigen elicit a strong dose-dependent immunogenic response 
(as measured by HAI antibody titer) to a single intranasal administration at doses ranging from 
2.5×108 to 2.5×1010 vp. A booster dose administered 21 or 28 days later increased the response, 
indicating that an antivector immune response to the initial dose did not block a booster effect.  
Studies in mice and ferrets also showed protection from a lethal influenza virus challenge, even 
in the absence of a protective level of HAI antibody titers. A single intranasal dose of 2.5×109 vp 
or 2.5×1010 vp provided 100% protection from a lethal challenge in mice, and a single intranasal 
dose of 1×1010 vp or 2 intranasal doses of 1×108 vp 21 days apart provided 100% protection in 
ferrets. Furthermore, a study in mice showed protection from lethal challenge from vaccination 
administered 2 days before the challenge and protection elicited by an empty (no influenza gene 
insert) Ad5 vector. These findings suggest multiple mechanisms of action—perhaps including 
mucosal and innate immunity as well as humoral immunity—for this vaccine construct. 
Biodistribution studies of Ad5-vectored influenza vaccines in CD-1 mice showed primarily 
localization to the olfactory bulb, lungs, and nasopharynx. At 3 weeks after vaccination, minimal 
residual virus was detected, and no evidence of widespread dissemination was seen, indicating 
that the Ad5 vector DNA was rapidly cleared from all tissues. A GLP (Good Laboratory 
Practice) study of AdVAV in rabbits showed localization of the vaccine in the trachea and 
esophagus through 2 days after the last dose, in the olfactory bulb through 14 days after the last 
dose, and in the nasal epithelium through the end of the study (90 days after the last dose of a 
3-dose series). As with the mouse studies, no evidence of widespread dissemination was seen, 
and the Ad5 vector DNA was rapidly cleared from all tissues except at the site of administration. 
Taken together, these biodistribution studies indicate that after intranasal delivery of NasoVAX 
the vector biodistribution is localized to tissues of the upper respiratory tract as opposed to a 
more widespread or systemic dissemination. Localization to the olfactory bulb was transient, 
consistent with other intranasally delivered compounds, and not associated with inflammation or 
clinical observations.  
In 4 nonclinical single-dose and repeat-dose toxicity studies of Ad5-vectored vaccines in mice 
and rabbits, no test article-related changes were observed except for the following effects: 

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• 
Inflammatory changes in the lung were observed in mice that received a 1×1010 vp dose 
and in a dose-dependent manner in mice that received 106 vp, 107 vp, or 108 vp doses. 
Observations of lung inflammation in the mouse studies is not surprising and is 
probably related to the dose volume used in these studies relative to the volume of the 
nasal cavity of mice as is evidenced by the greater lung involvement noted in the mouse 
studies that used a 50 µL dose volume compared to the mouse study that used a 25 µL 
dose volume. 
• 
A nonadverse inflammatory/immune response in the rabbits, ie, increases in fibrinogen 
and C-reactive protein concentrations, was observed in all groups (including controls), 
was most pronounced in samples collected 2 days after dosing, and resolved by the 
recovery sample collection. The inflammatory/immune response was likely related to 
minimal to mild nonadverse microscopic changes in the lung, which included alveolar 
histiocytosis, heterophil or mononuclear infiltration, and intra-alveolar subacute/chronic 
inflammation. 
The NOAEL established in New Zealand White rabbits in the GLP repeat-dose toxicity study for 
AdVAV was 1×1011 vp. 
2.5 
Previous Clinical Experience with Adenoviral Vectors 
The ability of RD-Ad5 vectors to adequately express the protein of interest following parenteral 
administration in the presence of pre-existing immunity to wild-type (WT) Ad5 has been a 
concern [Yang1994]. However, several lines of evidence, including clinical trials of earlier 
formulations of NasoVAX, suggest that anti-Ad5 immunologic components may not represent 
the same barrier to efficacy when the vector is administered using the intranasal route and that 
administration by this route may overcome pre-existing immunity to the adenovirus vector.  
A significant body of evidence supports the general safety of RD-Ad5 vectors, including lack of 
potential for replication and recombination with WT adenovirus. The Sponsor’s previous 
nonclinical and clinical experience with Ad5-vectored vaccines has shown no evidence 
suggestive of viral recombination in vaccinated subjects.  
2.6 
Clinical Trials of NasoVAX 
The immunogenicity and safety of Ad-5 vectored influenza vaccines has been evaluated in 2 
Phase 1 studies in healthy volunteers. These studies involved doses similar to the lowest dose 
being delivered in the this study or lower. The vaccines were well tolerated. Immune responses 
were weak but measurable despite the relatively low doses tested. The trials are summarized 
below, and additional details are provided in the current Investigator Brochure. 
In a 2002 study of an Ad5-vectored vaccine encoding the HA surface protein antigen from the 
A/Puerto Rico/8/34(H1N1) strain of influenza of 24 male health volunteers aged 20 to 31 years, 
6 subjects received 2 intranasal doses of 5×108 vp 28 days apart [Van Kampen 2005]. In addition 
to the intranasal vaccine recipients, 18 other subjects received 2 topical doses of either 4.8×109, 
4.8×1010, or 4.8×1011 vp. No SAEs or severe AEs were observed. For both administration sites, 
most (85%) of the side effects were mild in severity, 15% were moderate, and no serious 
reactions to the vaccine were observed either systemically or at the site of inoculation. The local 

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AEs reported in the intranasal group were discoloration (1 subject), burning (2 subjects), and 
bitter taste (1 subject). Systemic events of soreness, headache, nausea/vomiting, and muscle pain 
were reported for 1 subject each in the intranasal group.. Four of the 6 subjects who received the 
intranasal vaccine had increased HAI antibody titers after the primary dose, and this number 
increased to 5 after the booster dose. No correlation was observed between prevaccination Ad5 
antibody titers and HAI titer fold changes for intranasal administration. 
In a 2007 study of an Ad5-vectored vaccine encoding the HA surface protein antigen from the 
A/Vietnam/1203/2004(H5N1) influenza virus strain, 48 subjects were randomized for intranasal 
administration in groups of 12 to receive 5.0×107 vp, 2.4×108 vp, 3.3×109 vp, or placebo 28 days 
apart. A total of 36 women and 12 men aged 25 to 40 (mean 34.0) years were enrolled. No SAEs 
and no anaphylaxis, hives, or other allergic reactions were reported. The most common local 
reactogenicity events were headache, runny nose, sore throat, nasal congestion, and nasal 
irritation and were predominantly mild. Incidence rates of reactogenicity events, unsolicited AEs, 
and abnormal physical examination findings, and shift rates from normal to abnormal laboratory 
results were not statistically significantly different between active and placebo groups. Although 
only 1 subject (8.3%) in the highest dose group seroconverted, 4 of the 12 (33%) had increases in 
HAI titer. Pre-existing immunity to the adenovirus vector was not associated with influenza 
antibody response. 
2.7 
Study Rationale  
This study is designed to evaluate safety and immunogenicity of a monovalent 
A/California/04/2009(H1N1)-like strain version of NasoVAX, testing doses similar to and higher 
than those tested in previous Phase 1 studies. Exploratory endpoints will evaluate the breadth of 
antibody response and the ability of NasoVAX to induce cellular and mucosal immune 
responses.    
2.8 
Benefit/Risk Assessment 
On the basis of nonclinical and clinical study results to date, the efficacy issues associated with 
existing influenza vaccines, and the potential morbidity and mortality associated with influenza, 
NasoVAX is considered to have a positive benefit-risk profile for healthy adults aged 18 to 49. 

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3 STUDY OBJECTIVES AND ENDPOINTS 
 
OBJECTIVES 
ENDPOINTS 
Primary Objective 
• To describe the safety profile of 
NasoVAX in healthy adults when 
administered by intranasal spray at 
a single dose of 1×109, 1×1010, or 
1×1011 vp   
• Reactogenicity: counts and percentages of subjects 
with local events (nasal irritation, sneezing, nasal 
congestion, cough, sore throat, change in smell, 
change in taste, change in vision, eye pain) and 
systemic events (headache, fatigue, muscle ache, 
nausea, vomiting, diarrhea, chills, fever) for 
14 days after vaccination 
• AEs: counts and percentages of subjects with AEs 
from Day 1 to Day 29; MAEs, SAEs, NCIs from 
Day 1 to Day 181 
Secondary Objective 
• To evaluate the humoral immune 
response to NasoVAX when 
administered by intranasal spray at 
a single dose of 1×109, 1×1010, or 
1×1011 vp 
• Antibody level measured by HAI in serum: 
o GMT: the antilog of the mean of the log-
transformed titers 
o GMR: the ratio of postvaccination and 
prevaccination GMTs within the same dose 
group  
o SPR: the percentage of subjects with a HAI 
titer ≥ 1:40 
o SCR: the percentage of subjects with either a 
baseline HAI titer < 1:10 and a 
postvaccination titer ≥ 1:40 (which is 4 times 
the assay lower limit of quantitation), or a 
baseline HAI titer ≥ 1:10 and a 4-fold increase 
in postvaccination HAI titer relative to 
baseline 
• Antibody level measured by microneutralization 
in serum: 
o GMT  
o Responder rate: the proportion of subjects with 
2-fold and 4-fold rise since baseline 

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OBJECTIVES 
ENDPOINTS 
Exploratory Objectives 
• To evaluate the cellular immune 
response to NasoVAX when 
administered by intranasal spray at 
a single dose of 1×109, 1×1010, or 
1×1011 vp 
• SFUs to HA peptides measured by enzyme-linked 
ELISpot in PBMCs: 
o Geometric mean SFUs 
o Responder rate 
• To evaluate the mucosal immune 
response NasoVAX when 
administered by intranasal spray at 
a single dose of 1×109, 1×1010, or 
1×1011 vp  
• IgA antibody level measured by ELISA: 
o GMT  
o GMR 
• To evaluate the humoral immune 
response against nonrepresented 
influenza strains after NasoVAX 
administration 
• Antibody level measured by HAI and 
microneutralization in serum against each strain 
tested:  
o GMT  
o GMR  
o Responder rate: the number and percentage of 
subjects with 2-fold and 4-fold rise since 
baseline 
• To evaluate the effect of predose 
Ad5 serum antibody levels on the 
immunogenicity of NasoVAX 
• Predose Ad5 antibody GMT measured by 
microneutralization in serum 
• Day 29 GMR and responder rate from antibody 
level measured by HAI in serum 
• To compare immunogenicity 
results to those obtained from 
banked samples from a previous 
study of licensed seasonal vaccine 
in a similar subject population 
• Antibody level measured by HAI in serum: 
o GMT 
o GMR  
o SPR 
o SCR 
• Antibody level measured by microneutralization 
in serum: 
o GMT  
o Responder rate 
• SFUs to hemagglutinin peptides measured by 
ELISpot in PBMCs: 
o Geometric mean SFUs 
o Responder rate 
• IgA antibody level measured by ELISA: 
o GMT  
o GMR 
 

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4 STUDY DESIGN 
4.1 
Overall Study Design 
The Schedule of Events showing time points for all study procedures is provided in Section 1.2. 
This is a Phase 2a, randomized, double-blind, placebo-controlled trial to evaluate the safety, and 
immunogenicity of NasoVAX in healthy adults 18 to 49 years of age. Subjects will be screened 
within 28 days of randomization (Day 1). Approximately 60 subjects who meet all inclusion and 
no exclusion criteria and provide written informed consent will be enrolled into 3 sequential 
cohorts of 20 subjects each defined by the viral particle dose (1×109, 1×1010, and 1×1011 vp). 
Within each cohort and its sentinel group, subjects will be randomized in a 3:1 ratio to receive 1 
intranasal dose of NasoVAX or placebo (Day 1) as shown in Table 1.  
Table 1 
NasoVax Study Design 
Cohort 
Dose (vp) 
Number of Subjects 
NasoVAX 
Placebo 
1 
1×109 
15 
5 
2 
1×1010 
15 
5 
3 
1×1011 
15 
5 
Study Total Target 
45 
15 
Total 
60 
A sentinel group of 5 subjects from each cohort will be dosed. Dosing of the remainder of each 
cohort may proceed after the last sentinel subject completes Day 8 if no events meeting stopping 
criteria have occurred. The SRC, consisting of the Investigator, the Medical Monitor, and a 
Sponsor Representative, will review AE, reactogenicity, and laboratory data through at least Day 
8 for all subjects in each cohort before subjects are randomized to the next higher dose. If any 
event meeting stopping criteria occur, the SRC will review all available safety information 
before additional patients are dosed. Stopping criteria are as follows: 
• 
Occurrence of any related SAE or Grade 4 AE 
• 
Occurrence of 2 Grade 3 AEs in the same organ system 
• 
Occurrence of the same Grade 3 laboratory abnormality in 2 or more subjects 
Each subject will record reactogenicity (local events, systemic events, and oral temperature) and 
whether any medication or treatment was used for the symptom(s) in a diary daily for 14 days 
after the NasoVAX/placebo dose. Each subject will be contacted by telephone on Day 2 for 
safety assessment and review of the diary. Subjects will return to the investigational site on Days 
4, 8, 15, 29, 91, and 181 for safety and immunogenicity assessments. At each visit, the subject 
will also be asked about the interim medical history and use of any medications. 
A serum sample will be collected from each subject for evaluation of influenza HAI assay 
against A/California/04/2009 predose on Day 1 on Days 4, 8, 15, 29, 91, and 181; Ad5 antibody, 
microneutralization assay against both A/California/04/2009(H1N1) and nonrepresented strains, 

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and HAI against nonrepresented strains will also be evaluated at Days 1 and 29. A whole blood 
sample will be collected from each subject and processed to isolate PBMCs for evaluation of T-
cell responses by ELISpot predose on Day 1 and on Day 8.  
A nasopharyngeal swab sample will be collected from each subject at Screening and on Days 4, 
8, 15, 29, and 91 to measure concentration of the Ad5 vector for assessment of vaccine vector 
shedding by quantitative polymerase chain reaction (qPCR) assay. Once a negative result is 
obtained, later samples may not be tested. ELISA for measurement of IgA will also be performed 
on the swab samples from Screening and Day 29 for evaluation of mucosal immune response. 
Banked samples from a previous study of licensed seasonal vaccine in a similar subject 
population will be analyzed alongside samples collected in this study. 
All AEs and medications will be recorded from signing of the ICF to Day 29. Thereafter to the 
end of the study, only MAEs, NCIs, SAEs, immunosuppressive medications (see list in 
Appendix 3), and vaccines will be recorded. Samples for clinical laboratory tests (hematology, 
serum chemistry, urinalysis) will be collected at Screening and on Days 8 and 29. A complete 
physical examination and vital signs will be performed at Screening and predose on Day 1, and 
targeted and symptom-driven physical examinations will be performed and vital signs measured 
2 hours postdose and on Days 4, 8, 15, and 29. An ECG will be performed at Screening and on 
Day 29. If a subject experiences acute symptoms compatible with adenoviral infection within 28 
days after the NasoVAX/placebo dose, a sample will be collected for viral culture as clinically 
indicated. 
One interim analysis of humoral immunogenicity data and safety data (including summaries of 
AE, reactogenicity, concomitant medications and vaccines, vital signs, ECG, and laboratory data 
and listing of any viral culture results) will be conducted when all data through the Day 29 visit 
is available and monitored for all subjects. 
4.2 
Study Design Rationale 
4.2.1 
Population 
Healthy, immunocompetent adults aged 18 to 49 years were selected as the population for this 
study to minimize risk to subjects and to maximize the potential to produce an immune response. 
4.2.2 
Dose 
The initial dose to be tested in this study (1×109 vp) is in the range of intranasal doses that were 
shown to be safe and modestly immunogenic in earlier clinical trials of NasoVAX (Section 2.6). 
Escalation is planned to the NOAEL (1×1011 vp) established in the GLP repeat-dose toxicology 
study of AdVAV in New Zealand White rabbits (Section 2.4). 

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4.2.3 
Assessments 
Safety 
An evaluation of safety is the primary objective for this study of NasoVAX that will evaluate 
doses higher than tested in the previous Phase 1 studies of this adenoviral vector. Safety 
assessments are standard for early-phase clinical trials and are in accordance with the US Food 
and Drug Administration’s (FDA’s) guidance on preventive vaccine clinical trials [FDA 2007b]. 
Reactogenicity events were requested by the FDA for intranasal administration. 
Although NasoVAX is constructed from an RD adenoviral vector, there is a theoretical risk of 
recombination with WT adenovirus. Clinical illness caused by adenovirus can present as a wide 
variety of syndromes, including upper respiratory infection, pneumonia, conjunctivitis, and 
gastroenteritis [Adenoviruses 2015]. Subjects presenting with a potentially compatible clinical 
syndrome after vaccination will have appropriate specimens obtained for viral culture. 
On the basis of animal biodistribution studies, it is expected that carriage of the vaccine vector 
will be transient and limited to the upper respiratory tract. Swab samples will be obtained for 
adenovirus qPCR to determine how long the vector persists at the site of administration.   
Immunogenicity 
Humoral immune response to the influenza HA protein as measured by HAI is a recognized 
surrogate of protection [FDA 2007a] and will be important in selecting the optimum dose for 
further clinical development.   
4.3 
Number of Sites and Subjects 
The study will be conducted at 1 site in the United States. 
Sixty subjects will be enrolled. 
4.4 
Duration of Subject Participation and Study 
Each subject will participate in the study for approximately 7 months.  
The end of the study is defined as the last visit of the last subject participating in the study. The 
expected duration of the study is approximately 9 months. 
 
 

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5 SUBJECT POPULATION 
The Investigator must keep a record (ie, a subject screening log) of subjects who are screened for 
this study. 
5.1 
Inclusion Criteria  
Subjects who meet all of the following criteria may be included in the study: 
1. Men and women 18 to 49 years of age, inclusive  
2. Good general health status as determined by the Investigator 
3. Adequate venous access for repeated phlebotomies 
4. Screening laboratory results within institutional normal range or Grade 1 elevation if the 
Investigator documents clinical insignificance. Creatine kinase or bilirubin may be Grade 
2 if associated with normal alanine aminotransferase (ALT) and aspartate 
aminotransferase (AST) and the Investigator considers the result not to be clinically 
significant due to vigorous exercise or Gilbert’s syndrome 
5. Negative drug and alcohol screen at Screening and predose on Day 1 
6. For women who have not been surgically sterilized or have laboratory confirmation of 
postmenopausal status, negative pregnancy test  
7. Willingness to practice a highly effective method of contraception that may include, but 
is not limited to, abstinence, sex only with persons of the same sex, monogamous 
relationship with a postmenopausal partner, monogamous relationship with vasectomized 
partner, vasectomy, surgical sterilization (hysterectomy, or bilateral tubal ligation, 
salpingectomy, or oophorectomy), licensed hormonal methods, intrauterine device (IUD), 
or consistent use of a barrier method (eg, condom, diaphragm) with spermicide for 28 
days after the NasoVAX/placebo dose 
8. Willingness to participate and comply with all aspects of the study through the entire 
study period, including nasopharyngeal swabs and blood and urine samples  
9. Provision of written informed consent  

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5.2 
Exclusion Criteria  
Subjects who meet any of the following criteria will be excluded from the study: 
1. Pregnant, possibly pregnant, or lactating women 
2. Household contacts of pregnant women, children <5 years of age, or 
immunocompromised individuals for the period up through 2 weeks postvaccination 
3. Persons who care for pregnant women, children <5 years of age, or immunocompromised 
individuals for the period up through 2 weeks postvaccination 
4. Body mass index >35.0 kg/m2 
5. Positive results for HIV, hepatitis B virus, or hepatitis C virus at Screening 
6. Asthma or other chronic lung disease that is greater than mild in severity. Specifically 
excluded are participants with the any of the following events in the past year: 
• Daily symptoms 
• Daily use of short acting beta 2 agonists 
• Use of inhaled steroids or theophylline 
• Use of pulse systemic steroids 
• Emergency care or hospitalization related to asthma or other chronic lung disease  
• Systemic steroids for asthma exacerbation 
7. History of diabetes mellitus (gestational diabetes is allowed if treatment was not required 
postpartum and serum glucose is currently in the normal range) 
8. History of coronary artery disease, arrhythmia, or congestive heart failure  
9. Clinically significant ECG abnormality as determined by the Investigator 
10. Poorly controlled hypertension (systolic blood pressure >150 mmHg or diastolic blood 
pressure >95 mmHg) at Screening or predose on Day 1 
11. History of anaphylaxis or angioedema 
12. Known allergy to any of the ingredients in the vaccine formulation 
13. History of chronic rhinitis, nasal septal defect, cleft palate, nasal polyps, or other nasal 
abnormality that might affect vaccine administration 
14. Previous nasal surgery or nasal cauterization 
15. Any symptoms of upper respiratory infection or temperature >38°C within 3 days before 
Day 1 
16. Any symptoms within 24 hours before Day 1 of upper respiratory illness of allergy flare-
up that, in the opinion of the Investigator, presents as nasal congestion or rhinorrhea that 
could inhibit the proper administration of the IP 

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17. Known or suspected malignancy, excluding non-melanoma skin cancers and other early 
stage surgically excised malignancies that the Investigator considers to be exceedingly 
unlikely to recur 
18. Immunocompromised individuals, including those who have used corticosteroids 
(including intranasal steroids), alkylating drugs, antimetabolites, radiation, immune-
modulating biologics, or other immunomodulating therapies within 90 days before Day 1 
or those who plan use during the study period 
19. Use of statin medication within 30 days before Day 1 (see list in Section 6.8.1) 
20. Receipt of intranasal medications (including over-the-counter medications) within 30 
days before Day 1 
21. Receipt of any IP within 30 days before Day 1 
22. Receipt of any vaccine within 30 days before Day 1 
23. Receipt of intranasal vaccine within 90 days before Day 1 
24. Receipt of any influenza vaccine within 6 months before Day 1  
25. Any change in medication for a chronic medical condition within 30 days before Day 1 
26. Past regular use or current use of intranasal illicit drugs 
27. Smokers, including smoking of any type (eg, cigarettes, electronic cigarettes, 
marijuana). Prior smokers must have quit smoking at least 30 days before Day 1. 
28. Any medical, psychiatric, or social condition or occupational or other responsibility that 
in the judgment of the Investigator would interfere with or serve as a contraindication to 
protocol adherence, assessment of safety (including reactogenicity), or a subject’s ability 
to give informed consent 

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6 INVESTIGATIONAL PRODUCTS 
6.1 
Formulation, Packaging, and Administration 
6.1.1 
NasoVAX 
NasoVAX uses the RespirVec platform developed by Altimmune for intranasally administered 
vaccines, an E1/E3-deleted, RD-Ad5 vector that expresses the protein of interest within 
respiratory epithelial cells. In the case of NasoVAX, the vector contains a genetic insert encoding 
the HA surface protein antigen from influenza type A or B. The recombinant Ad5 vector lacks 
the E1 region of the viral genome (nucleotides 343 to 3511), which renders the virus RD and 
incapable of producing infectious virus particles upon entry into a host cell. An additional 
deletion of nucleotides 28132 to 30813 in the E3 region of the vector removes genes that are 
involved in evading the host immune response and are dispensable for virus replication. An 
expression cassette consisting of a cytomegalovirus transcriptional enhancer/promoter to drive 
the expression of the HA gene, a bioengineered HA gene, and a Simian Virus 40 polyadenylation 
signal has been inserted in place of the E1 gene sequences. Figure 1 provides a schematic 
diagram of the RD-Ad5 vector and identifies those sequences from the parent adenovirus 
genome that are retained in the vector.  
Figure 1 
Schematic Diagram of the Adenovirus Vector 
 
 
Numbers refer to base pair# in wild-type Ad5 sequence, GenBank ID AY339865.1. 
In this trial, the vector will contain a genetic insert encoding the HA surface protein antigen from 
an A/California/04/2009(H1N1)-like strain of influenza (AdcoCA09.HA).   
NasoVAX is manufactured by propagation of the RD-Ad5 vector in replication-permissive 
PER.C6 cells, followed by purification of the virus from the infected cell harvest, and the final 
product includes the following excipients: Tris HCl (pH 7.4), histidine, sucrose, sodium chloride, 
magnesium chloride, polysorbate 80, ethylenediaminetetraacetic acid, and ethanol. 
 

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NasoVAX will be supplied in single-use glass vials each containing a nominal volume of 0.7 mL 
of a sterile, frozen suspension of vaccine formulated to deliver the nominal doses of 1×109, 
1×1010, or 1×1011 vp. According to the release specifications for NasoVAX, the actual dose to be 
administered may be up to approximately 3-fold lower or higher than the nominal dose. The 0.5 
mL NasoVAX doses will be administered as an intranasal spray using a 1 mL syringe fitted with 
a Teleflex LMA MAD Nasal Intranasal Mucosal Atomization Device. Further information on 
dose preparation and administration is provided in the pharmacy manual. 
6.1.2 
Placebo 
The placebo is normal saline provided by the investigational site.  
The 0.5 mL placebo doses will be administered as an intranasal spray using a 1 mL syringe fitted 
with a Teleflex LMA MAD Nasal Intranasal Mucosal Atomization Device and will be identical 
in appearance to NasoVAX doses. Further information on dose preparation and administration is 
provided in the pharmacy manual. 
6.2 
Labelling 
All IPs will be labelled in accordance with applicable regulatory guidelines.  
6.3 
Storage  
NasoVAX will be stored in a secure place under appropriate storage conditions at -20°C ± 5°C. 
Normal saline will be stored in a secure place in accordance with storage conditions on the 
product label. 
6.4 
Blinding and Unblinding 
Investigators, subjects, and all study staff with direct subject contact will be blinded to 
assignment to NasoVAX or placebo. A designated unblinded pharmacist (or otherwise qualified 
person) at the site will assign the NasoVAX or placebo based on the block randomization table 
provided by the unblinded statistician and prepare the blinded syringe for dispensing to the 
subject. The individual performing these tasks will have no contact with the subjects and 
minimize contact with other site study personnel. 
Unblinding of vaccine assignment is discouraged. In the event of a medical emergency, for 
which the identity of the assignment is critical to the care of a subject, the Investigator will call 
the Medical Monitor to discuss. In the event that unblinding is deemed necessary, a designated 
unblinded study team member will provide the assignment to the Medical Monitor who will 
provide the information to the Investigator.  
Sponsor personnel and other members of the study team will have no access to data aggregated 
by treatment arm until after the interim analysis (see Section 12.10). Sponsor personnel and other 
members of the study team will have no access to any individual treatment assignment except as 
needed to satisfy requirements for prompt reporting of SAEs to Regulatory Authorities. In this 
case, unblinded data from an individual subject will be provided immediately to the Medical 
Monitor. 

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6.5 
Randomization and Timing of NasoVAX/Placebo  
Subjects will be enrolled into 3 sequential cohorts of 20 subjects each defined by the viral 
particle dose (1×109, 1×1010, or 1×1011 vp). Within each sentinel group and cohort, subjects will 
be randomized at a ratio of 3:1 ratio to receive 1 intranasal dose of NasoVAX or placebo on 
Day 1.  
A sentinel cohort of 5 subjects from each cohort will be dosed. Dosing of the remainder of each 
cohort may proceed after the last sentinel subject completes Day 8 if no events meeting stopping 
criteria (Section 6.6) have occurred. The SRC, consisting of the Investigator, the Medical 
Monitor, and a Sponsor Representative, will review all AE, reactogenicity, and laboratory data 
through Day 8 for all subjects in each cohort before subjects are randomized to the next higher 
dose.  
6.6 
Stopping Criteria 
If any event meeting the following criteria occurs, the SRC will review all available safety 
information before additional patients are dosed: 
• 
Occurrence of any related SAE or Grade 4 AE 
• 
Occurrence of 2 Grade 3 AEs in the same organ system 
• 
Occurrence of the same Grade 3 laboratory abnormality in 2 or more subjects 
6.7 
Accountability, Dispensing, and Destruction 
The Investigator (or designee) will maintain an accurate record of the receipt of each IP as 
shipped by the Sponsor (or designee), including the date received. In addition, an accurate IP 
disposition record will be kept, specifying the amount dispensed for each subject and the dates of 
dispensation and any returns.   
Sponsor approval is required for on-site destruction of all used IP and shipment of all unused IP 
back to the Sponsor at the completion of the study and once all reconciliation has occurred.   
6.8 
Prior and Concomitant Treatments 
All concomitant treatments, including over-the-counter medicines, will be recorded from 30 days 
before the NasoVAX/placebo dose through 28 days after the NasoVAX/placebo dose and coded 
using the WHO Drug Dictionary. Only immunosuppressive medication (see list in Appendix 3) 
and vaccines will be recorded from Day 29 to the end of the study. 
6.8.1 
Prohibited Prior Medications and Vaccines 
Subjects who received any of the following medications and vaccines may not be enrolled: 
• 
Corticosteroids, alkylating drugs, antimetabolites, radiation, immune-modulating 
biologics, or other immunosuppressive therapies within 90 days before Day 1 (see list 
in Appendix 3) 

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• 
Immunomodulating medications, including intranasal steroids, within 30 days before 
Day 1 
• 
Statin medication within 30 days before Day 1 (including atorvastatin [Lipitor], 
fluvastatin [Lescol, Lescol XL], lovastatin [Mevacor, Altoprev], pravastatin 
[Pravachol], rosuvastatin [Crestor], simvastatin [Zocor], pitavastatin [Livalo]) 
• 
Intranasal medications, including over-the-counter medications within 30 days before 
Day 1 
• 
IP within 30 days before Day 1 
• 
Any vaccine within 30 days before Day 1 
• 
Intranasal vaccine within 90 days before Day 1 
• 
Influenza vaccine within 6 months before Day 1  
6.8.2 
Prohibited Concomitant Medications and Vaccines 
The following medications and vaccines are prohibited during the study: 
• 
Statin medication from Day 1 to Day 29 (see list in Section 6.8.1) 
• 
Corticosteroids, alkylating drugs, antimetabolites, radiation, immune-modulating 
biologics, or other immunosuppressive therapies at any time during the study (see list in 
Appendix 3) 
• 
Any vaccine from Day 1 to Day 29  
• 
Any influenza vaccine other than NasoVAX within 90 days after NasoVAX/placebo 
dose (receipt of influenza vaccine other than NasoVAX is discouraged through the end 
of the study) 
6.9 
Contraception 
All subjects must practice a highly effective method of contraception that may include, but is not 
limited to, abstinence, sex only with persons of the same sex, monogamous relationship with a 
postmenopausal partner, monogamous relationship with vasectomized partner, vasectomy, 
surgical sterilization (hysterectomy, bilateral tubal ligation, salpingectomy, or oophorectomy), 
licensed hormonal methods, IUD, or consistent use of a barrier method (eg, condom, diaphragm) 
with spermicide through Day 29. 
6.10 Compliance 
All IPs will be administered by trained personnel at the investigational site. 
 

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7 STUDY ASSESSMENTS AND DATA COLLECTION 
Refer to Section 1.2. for the Schedule of Events. 
7.1 
Demographics 
Demographic data and other baseline characteristics will be obtained and recorded at Screening. 
7.2 
Medical History 
A standard medical, medication, and surgical history will be obtained and recorded at Screening. 
7.3 
Reactogenicity (Diary) 
Each subject will be provided with a diary and a thermometer after each dose. The subjects will 
record and provide severity grade (except for temperature) for the following items in a diary 
(sample provided in Appendix 2) and whether any medication or treatment was used for the 
symptom(s) daily for the first 14 days after dosing. 
• 
Local events: nasal irritation, sneezing, nasal congestion, cough, sore throat, change in 
smell, change in taste, change in vision, eye pain 
• 
Systemic events: headache, fatigue, muscle ache, nausea, vomiting, diarrhea, chills  
• 
Oral temperature  
If there are any events ongoing after the diary reporting period, these events will be followed 
until resolution and the stop date recorded. The Investigator (or Subinvestigator) will review the 
diary with the subject. Any changes or comments to the subject’s diary by the Investigator (or 
Subinvestigator) must be made on the diary and initialed and dated by the Investigator (or 
Subinvestigator).   
A reactogenicity event recorded on the diary will not be recorded as an AE unless it meets the 
criteria of an SAE. 
7.4 
Adverse Events (Including Medically Attended Events, Serious Adverse 
Events, and New-onset Chronic Illnesses) 
See Section 9. 
7.5 
Height and Weight 
Height and weight will be measured and recorded at Screening. 
7.6 
Complete Physical Examination 
Examination of the following systems will be performed at the time points specified in the 
Schedule of Events and as clinically indicated: cardiovascular; dermatological; head, eyes, ear, 

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nose, and throat; extremities; gastrointestinal; musculoskeletal; neurological ophthalmological; 
neurological; respiratory.  
Any clinically significant change in physical examination finding will be recorded as an AE (see 
Section 9.5). 
7.7 
Targeted and Symptom-driven Physical Examination 
Examination of the respiratory and head, eyes, ear, nose, and throat systems and any additional 
systems as indicated by signs or symptoms reported by the subject will be performed at the time 
points specified in the Schedule of Events and as clinically indicated. An otorhinoscopic 
examination and visual examination of the nasopharynx will be conducted with findings 
recorded on a structured evaluation form.  
Any clinically significant change in physical examination finding will be recorded as an AE (see 
Section 9.5). 
7.8 
Vital Signs 
At the time points specified in the Schedule of Events and before any blood sample collection, 
systolic and diastolic blood pressure and pulse will be measured and recorded using a 
semiautomatic recording device with an appropriate cuff size after the subject has been in a 
supine position for at least 5 minutes. Oral temperature will also be measured. Any clinically 
significant abnormal vital sign value will be recorded as an AE (see Section 9.5). 
7.9 
Electrocardiogram 
At the time points specified in the Schedule of Events and before any blood sample collection, a 
12-lead ECG will be performed after the subject has been in a supine position for at least 
5 minutes. Interpretation (normal, abnormal not clinically significant, abnormal clinically 
significant) will be recorded. Any clinically significant change in ECG interpretation will be 
recorded as an AE (see Section 9.5). 
7.10 Blood Samples 
7.10.1 
Safety Laboratory Tests 
Samples for the following tests will be collected, processed, and shipped to the laboratory in 
accordance with instructions in the laboratory manual at the time points specified in the Schedule 
of Events: 
• 
Hematology: hemoglobin, platelet count, white blood cell count with differential 
(absolute or percent counts of neutrophils, lymphocytes, monocytes, basophils, 
eosinophils) 
• 
Serum chemistry: alkaline phosphatase, ALT, AST, bicarbonate, bilirubin, chloride, 
creatine kinase, creatinine, glucose, potassium, sodium, urea nitrogen  
• 
Urinalysis: glucose, protein 

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Any laboratory abnormality deemed clinically significant by the Investigator should be recorded 
as an AE (see Section 9.5). 
7.10.2 
Serum Samples (Immunogenicity) 
Serum samples will be collected and processed at the time points specified in the Schedule of 
Events. Collection, processing, labelling, storage and shipping instructions for these samples are 
provided in the laboratory manual. 
Influenza virus HAI assay against A/California/04/2009(H1N1) will be performed on all samples 
collected.  
Ad5 microneutralization, influenza microneutralization against all strains, and HAI against 
nonrepresented strains will be performed on samples collected on Days 1 and 29 only. A larger 
serum sample will be collected on Days 1 and 29 for these assays. 
7.10.3 
Peripheral Blood Mononuclear Cells (Immunogenicity) 
Whole blood samples will be collected and processed to isolate PBMCs at the time points 
specified in the Schedule of Events. Collection, processing, labelling, storage, and shipping 
instructions for these samples are provided in the laboratory manual. 
ELISpot will be performed on all samples for measurement of T-cell activity. 
7.11 Pregnancy Tests 
A serum or urine sample will be collected from all women who have not been surgically 
sterilized or have laboratory confirmation of postmenopausal status and tested at the time points 
specified in the Schedule of Events. 
7.12 Nasopharyngeal Swabs 
A nasopharyngeal swab sample will be collected and processed at the time points specified in the 
Schedule of Events. Collection, processing, labelling, storage, and shipping instructions for these 
samples are provided in the laboratory manual. Nasopharyngeal swabs are not obtained on the 
day of dosing in order not to disturb the nasal mucosa. A qPCR assay for detection of the RD 
vector will be performed on swab samples to measure concentration of the RD vector. Once a 
negative result is obtained, later samples may not be tested. Screening and Day 29 samples will 
also be tested for influenza IgA by ELISA.   
7.13 Viral Culture 
A sample (as clinically indicated) for viral culture will be collected from any subject who 
experiences acute symptoms compatible with possible adenoviral infection within 28 days after 
the NasoVAX/placebo dose. The sample will be collected, processed, and shipped to the 
laboratory in accordance with instructions in the laboratory manual. 

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8 STUDY VISITS 
8.1 
Screening (Within 28 Days Before Day 1) 
The subject will be screened to assess eligibility criteria. The following assessments and 
procedures will be performed: 
• Written informed consent 
• Demographics 
• Medical history 
• Concomitant medications (including vaccines) recording 
• Complete physical examination 
• Height and weight 
• ECG 
• Vital signs 
• Drug and alcohol screen 
• Collection of laboratory samples: 
o Hepatitis B and C and HIV tests 
o Clinical laboratory tests (hematology, serum chemistry, urinalysis) 
o Serum pregnancy test 
o Nasopharyngeal swab 
8.2 
Dosing Period 
If at any time in the Dosing Period (Days 1 to 29) the subject experiences acute symptoms 
compatible with adenoviral infection, a sample for viral culture will be collected.  
8.2.1 
Day 1 
The following procedures will be performed before NasoVAX/placebo administration: 
• Concomitant medications (including vaccines) recording 
• AE assessment 
• Complete physical examination 
• Vital signs 
• Drug and alcohol screen  
• Urine pregnancy test 

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• Sample collection: 
o Serum for humoral response (including serum for additional assays [see Section 
7.10.2 and the laboratory manual for details]) 
o Whole blood sample for isolation of PBMCs for cellular response 
• Eligibility criteria check 
Upon determination that a subject meets all eligibility criteria, the subject will be randomized to 
treatment assignment (as described in Section 6.5) and NasoVAX/placebo administered. The 
subject will be instructed not to blow his/her nose for 30 minutes after dosing. 
The following procedures will be performed 2 hours after NasoVAX/placebo administration: 
• Targeted and symptom-driven physical examination 
• Vitals signs 
Before discharge from the unit, the subject will be given a diary and instructed to record 
temperature, local events, and systemic events at the same time today and each day and whether 
any medication or treatment was used for the symptom(s) for the next 14 days. The subject will 
also be instructed that, if any event is ongoing for more than 14 days after the dose, to follow the 
event until resolution and report the stop date. The subject will be instructed to bring the diary 
back to the unit at the next visit.   
Before discharge from the unit, the following procedures will also be performed. 
• Concomitant medications recording 
• AE assessment 
8.2.2 
Day 2 (Telephone Contact) 
The following procedures will be performed: 
• Review of diary 
• Concomitant medications (including vaccines) recording 
• AE assessment 
8.2.3 
Day 4 (± 1 Day) 
The following procedures will be performed: 
• Review of diary 
• Targeted and symptom-driven physical examination 
• Vitals signs 
• Concomitant medications (including vaccines) recording 
• AE assessment 

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• Sample collection: 
o Serum for humoral response 
o Nasopharyngeal swab 
8.2.4 
Day 8 (± 1 Day) 
The following procedures will be performed: 
• Review of diary 
• Targeted and symptom-driven physical examination 
• Vitals signs 
• Concomitant medications (including vaccines) recording 
• AE assessment 
• Sample collection: 
o Clinical laboratory tests (hematology, serum chemistry, urinalysis) 
o Serum for humoral response 
o Whole blood sample for isolation of PBMCs for cellular response 
o Nasopharyngeal swab 
8.2.5 
Day 15 (± 1 Day) 
The following procedures will be performed: 
• Review of diary 
• Targeted and symptom-driven physical examination 
• Vitals signs 
• Concomitant medications (including vaccines) recording 
• AE assessment 
• Sample collection: 
o Serum for humoral response 
o Nasopharyngeal swab 
8.2.6 
Day 29 (± 3 Days) 
The following procedures will be performed: 
• Targeted and symptom-driven physical examination 
• Vitals signs 
• Concomitant medications (including vaccines) recording 

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• AE assessment 
• Urine pregnancy test 
• ECG 
• Sample collection: 
o Clinical laboratory tests (hematology, serum chemistry, urinalysis)  
o Serum for humoral response (including serum for additional assays [see Section 
7.10.2 and the laboratory manual for details]) 
o Nasopharyngeal swab 
8.3 
Follow-up Period 
8.3.1 
Day 91 (± 10 Days) 
The following procedures will be performed: 
• Recording of immunosuppressive medications (see list in Appendix 3) and vaccines 
• Assessment of SAEs, MAEs, and NCIs 
• Sample collection: 
o Serum for humoral response 
o Nasopharyngeal swab 
8.3.2 
Day 181 (± 10 Days) 
The following procedures will be performed: 
• Recording of immunosuppressive medications (see list in Appendix 3) and vaccines 
• Assessment of SAEs, MAEs, and NCIs 
• Sample collection: 
o Serum for humoral response 

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9 ADVERSE EVENTS 
9.1 
Definitions 
9.1.1 
Adverse Event 
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have a causal relationship 
with this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of an IP, 
whether or not related to the IP. 
The term AE is used to include any AE whether serious or nonserious. 
9.1.2 
Medically Attended Adverse Event 
An MAE is an AE resulting in hospitalization, emergency room visit, or visit to or from medical 
personnel (other than routine health care visits). 
9.1.3 
New-onset Chronic Illness  
An NCI is an AE that is new (ie, not present at baseline) and typically chronic. The eCRF will 
provide a field in which the Investigator will indicate whether or not the AE recorded is an NCI. 
Because of the significance of this designation for the subject’s health and for evaluation of 
vaccine safety, NCIs are expected to be diagnoses, not symptoms, and the Investigator should 
record sufficient data in the source document to support the diagnosis. 
9.1.4 
Serious Adverse Event 
An AE or suspected adverse reaction is considered serious (an SAE) if, in the view of either the 
Investigator or Sponsor, it results in any of the following outcomes: 
• Death 
• Life-threatening (An AE is considered life-threatening if, in the view of either the 
Investigator or Sponsor, its occurrence places the patient or subject at immediate risk of 
death. It does not include an AE that, had it occurred in a more severe form, might have 
caused death.) 
• Inpatient hospitalization or prolongation of existing hospitalization 
• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• A congenital anomaly/birth defect 
Life-threatening means that the subject was at immediate risk of death at the time of the SAE; it 
does not refer to a serious AE that hypothetically might have caused death if it were more severe. 
Hospitalization does not include same day surgery, elective surgery, optional admission not 

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associated with a precipitating AE (ie, elective cosmetic surgery), or hospitalization planned 
before the start of the study for a pre-existing condition that has not worsened. Persistent or 
significant disability or incapacity means that there is a substantial disruption of a person’s 
ability to carry out normal life functions. 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, they 
may jeopardize the patient or subject and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias 
or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
If it is not certain that an event meets the above definitions of an SAE, contact the Medical 
Monitor to discuss. 
9.2 
Reporting Responsibilities and Periods 
It is the responsibility of the Investigator or Subinvestigator(s) to perform periodic assessment of 
AEs. AEs spontaneously reported by the subject or reported in response to an open question from 
the study personnel (eg, ‘Have you had any health problems since the previous visit/you were 
last asked?’) or revealed by observation will be recorded.  
All AEs (including MAEs, NCIs, and SAEs) with onset after signing of the ICF until Day 29 will 
be recorded. Thereafter to the end of study, only MAEs, NCIs, and SAEs will be recorded. Data 
describing AEs will be recorded in the subject’s medical and as appropriate, an SAE report form. 
SAEs will be reported to the Sponsor as described in Section 9.7. 
9.3 
Recording of Adverse Events 
An AE should be recorded individually in the study subject’s own words (verbatim) unless, in 
the opinion of the Investigator, clarification of the subject’s verbatim language is necessary or 
the AEs constitute components of a recognized condition, disease, or syndrome. In the latter 
case, the condition, disease or syndrome should be named rather than each individual symptom. 
The AE term will subsequently be coded using MedDRA. 
The AE term, date of AE onset, date of AE resolution (if applicable), severity, causality, action 
taken for the AE, outcome and whether or not the AE is an MAE, NCI, and or SAE will be 
recorded. 

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9.4 
Assessment of Adverse Events 
9.4.1 
Severity 
The Investigator will grade severity of AEs in accordance with Toxicity Grading Scale for 
Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials 
(Appendix 1). If an appropriate listing is not present in this table for an AE, the AE will be 
graded as follows: 
• Grade 1 (Mild) – No interference with daily activity 
• Grade 2 (Moderate) – Some interference with daily activity but medical intervention not 
required (eg, doctor visit and/or prescription medicine); over-the-counter medicine 
permitted 
• Grade 3 (Severe) – Prevents daily activity and requires medical intervention (eg, doctor 
visit and/or prescription medicine) 
• Grade 4 (Potentially Life-threatening) – Emergency room visit or hospitalization 
9.4.2 
Relatedness (Causality) 
The Investigator will assess causality (relationship to NasoVAX/placebo) of AEs as follows:  
• Related – Reasons to consider an AE related to treatment may include, but are not 
limited, to the following: 
o Timing of the event relative to the administration of the IP 
o Location of the AE relative to the site of IP administration 
o Likelihood based on experience with similar products 
o A biologically plausible explanation based on the mechanism of action or mode of 
delivery of the treatment 
o The AE is repeated on subsequent treatments. 
o No other explanation is likely. 
• Unrelated – An AE with no temporal association with the IP but rather related to other 
etiologies such as concomitant medications or conditions or subject’s known clinical state 
9.5 
Clinical Laboratory, Physical Examination, Electrocardiogram and Vital 
Sign Abnormalities 
Any abnormal laboratory result, physical examination finding, ECG interpretation, or vital sign 
measurement considered clinically significant by the Investigator will be recorded as an AE. A 
clinically significant laboratory abnormality is a confirmed abnormality (by repeat test) that is 
changed sufficiently from screening/baseline so that in the judgment of the Investigator a change 
in management is warranted. This alteration may include monitoring the laboratory test further, 
initiating other diagnostic tests or procedures, changing ongoing treatment, or administering new 
treatment.   

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Whenever possible, the underlying medical diagnosis (eg, anemia) will be recorded as the AE 
term. Repeated additional assessments required to establish the significance and etiology of an 
abnormal result should be obtained when clinically indicated.  
A reactogenicity event recorded on the diary will not be recorded as an AE unless it meets the 
criteria of an SAE. 
9.6 
Pregnancy 
Pregnancy itself is not regarded as an AE unless there is a suspicion that the IP may have 
interfered with the effectiveness of a contraceptive medication. Pregnancy in a subject’s partner 
is not considered an AE. Congenital abnormalities/birth defects and spontaneous miscarriages 
should be reported and handled as SAEs. Elective abortions without complications should not be 
handled as AEs. The outcome of a pregnancy will be followed-up and documented even if the 
subject as withdrawn from the study. See Section 10 for further information on reporting of 
pregnancy.  
An induced elective abortion to terminate a pregnancy without medical reason is not regarded as 
an AE. However, an induced therapeutic abortion to terminate a pregnancy because of 
complications or medical reasons must be reported as an SAE. The underlying medical diagnosis 
for this procedure should be reported as the SAE term. A spontaneous abortion in a study subject 
is always considered an SAE. 
9.7 
Reporting of Serious Adverse Events  
SAEs must be reported to the Sponsor or designee within 1 business day of becoming aware of 
the event. If at the time the Investigator initially reports an SAE, the event has not resolved, the 
Investigator must provide a follow-up report as soon as it resolves (or upon receipt of significant 
information if the event is still ongoing).  
After review of an SAE report, the Medical Monitor may request additional documentation (eg, 
clinic or hospital records or procedure reports). 
9.8 
Follow-Up of Adverse Events 
A subject who experiences any AE, whether serious or not serious, will be monitored at 
appropriate intervals and receive appropriate treatment and medical supervision as clinically 
indicated. All AEs must be followed until resolution/stabilization or until a time that is mutually 
agreed upon between the Medical Monitor and the Investigator. Clinically significant laboratory 
abnormalities should be confirmed within 48 hours or as soon as clinically indicated and then 
followed weekly or as clinically indicated until resolution. 

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10 PREGNANCY 
The ICF will include information regarding reporting of pregnancy to the Sponsor and collection 
of information through the end of pregnancy that occurs in either a female subject or in a female 
partner of a male subject. If a female partner becomes pregnant, the Investigator will request 
consent from the partner to collect this information. 
Any pregnancy in a subject or in a subject’s partner and the subsequent outcome (spontaneous 
miscarriage, elective termination, ectopic pregnancy, normal birth, or congenital abnormality) 
will be reported to the Sponsor. 
If a subject becomes pregnant during the study, she should be encouraged to complete all 
scheduled follow-up unless there is a medical contraindication. 
 
 
 
 

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11 SUBJECT AND STUDY DISCONTINUATION 
11.1 Subject Withdrawal from the Study 
Subjects may be withdrawn from the study at any time for the following reasons: 
• 
Withdrawal of consent 
• 
Noncompliance with study requirements 
• 
Loss to follow-up 
• 
Death 
• 
Investigator discretion 
• 
Sponsor request 
• 
Termination of the study by the Sponsor (see Section 11.3). 
Subjects that are withdrawn from the study will not be replaced.   
11.2 Procedures for Subjects Who Terminate the Study Early 
Any subject who prematurely discontinues the study should be followed-up for at least 28 days 
after the last dose of any IP. 
If a subject prematurely discontinues the study on or before Day 29, then the procedures listed 
for Day 29 visit (Section 8.2.6) should be performed at the Early Termination Visit. If the subject 
is unwilling to return to the site for a visit, site staff will contact the subject by telephone to 
collect information about any AEs that have occurred since the last visit. 
If a subject prematurely discontinues the study after Day 29, site staff will contact the subject 
once by telephone to collect information about any MAEs, NCIs, or SAEs, that have occurred 
since the last visit. 
11.3 Study Discontinuation 
The entire study may be discontinued by the Sponsor for reasons including, but not limited to, 
the following: 
• 
An unexpected, significant, or unacceptable risk to the subjects enrolled in the study 
• 
Lack of evaluable or complete data 
• 
Decision to modify the NasoVAX development plan or to suspend or discontinue 
NasoVAX development  
• 
Medical or ethical reasons affecting the continued performance of the study 
• 
Difficulty in recruitment of subjects 

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12 STATISTICAL METHODS 
This section includes a brief description of the statistical analyses that will be performed in this 
study. A detailed statistical analysis plan (SAP) will be written and finalized before database 
snapshot for the interim analysis. Any deviation from the SAP will be described in the Clinical 
Study Report (CSR). All descriptive statistical analyses will be performed using SAS statistical 
software Version 9.2 or higher, unless otherwise noted. 
12.1 Analysis Populations 
The following analysis populations will be used: 
• 
Safety Population: All subjects who provide informed consent, are randomized, and 
receive at least 1 dose of IP. The Safety Population will be used for all safety analyses 
and will be analyzed according to the treatment received.  
• 
ITT Population: All subjects in the Safety Population who have HAI assay results on 
Day 1 and any postvaccination time point. The ITT Population is the secondary 
population for immunogenicity analyses and will be analyzed according to treatment as 
randomized.  
• 
PP Population: All subjects in the Safety Population that received the assigned dose of 
the test article in accordance with the protocol; have HAI assay results on Days 1, 15, 
and 29; and had no major protocol deviations affecting the primary immunogenicity 
outcomes as determined by the Sponsor prior to database lock. The PP Population is the 
primary population for immunogenicity analyses and will be analyzed as randomized. 
12.2 Analysis Conventions 
For all data analyses and summary tabulations, categories for analysis and presentation are the 
NasoVAX and placebo groups.  
Baseline is defined as the last nonmissing measurement prior to the administration of IP.  
Continuous variables will be presented by geometric means and 95% CIs for the immunogenicity 
endpoints and by summary statistics (eg, mean, and standard deviation [SD]) for other endpoints. 
Categorical variables will be presented by frequency distributions (percentages and 95% CIs) for 
the immunogenicity endpoints and frequency counts and percentages for other endpoints. 
12.3 Subject Disposition 
The number and percentage of subjects enrolled in the study, completing the study, and 
discontinuing the study will be presented in a tabular format. Reasons for discontinuation will 
also be summarized. 
Listings of randomized subjects who did not receive the IP and of subjects with other important 
protocol deviations (to be defined in the SAP, will be provided). 

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All analysis populations will be defined, and full descriptions of each population will be 
provided.  
12.4 Demographic and Bassline Characteristics 
Demographic parameters and other baseline characteristics (age, gender, race, ethnicity, body 
mass index) will be summarized by dose group for all subjects in the Safety Population. 
12.5 Prior and Concomitant Medications 
Prior and concomitant medications will be summarized by WHO Drug Dictionary anatomical 
therapeutic chemical level 3 and preferred term. 
12.6 Exposure 
All IP doses will be summarized. 
12.7 Safety Analyses 
The primary endpoint for evaluation of the safety profile is the number and percentage (95% CI) 
of subjects with solicited and unsolicited AEs recorded postvaccination. Safety analyses will be 
performed using the Safety Population. 
12.7.1 
Primary Endpoints  
Reactogenicity 
The number (percentage, 95% CI) of subjects with local reactions and systemic events will be 
summarized by dose group and overall. Reactogenicity events will also be summarized by 
severity.  
Adverse Events 
The number (percentage, 95% CI) of subjects with AEs from Day 1 to Day 29 (including MAEs, 
NCIs, SAEs) will be summarized for each MedDRA system organ class and preferred term and 
by dose group and overall. The number (percentage) of subjects with MAEs, with NCIs, and 
with SAEs from Day 1 to Day 181 will be summarized in a similar fashion. The number 
(percentage, 95% CI) of subjects with AEs by severity and by relationship to IP will also be 
summarized.   
Listings of AEs, MAEs, NCIs, and SAEs will be provided.  
12.7.2 
Clinical Laboratory Tests and Vital Signs 
Summary statistics for continuous parameters will be presented by dose group as follows: 
prevaccination, postvaccination, and change from prevaccination to postvaccination assessment. 
The number and percentage of subjects with postvaccination clinical laboratory values or vital 
sign values recorded as newly abnormal (ie, an event with an increase in the toxicity grade 

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relative to the baseline value and with a severity grade of moderate or higher) after study 
vaccination will be tabulated. Shift tables which cross-tabulate the prevaccination and 
postvaccination clinical laboratory values of each subject by severity grade will be prepared.  
12.7.3 
Electrocardiograms 
Summaries of the number and percentage of subjects with normal, abnormal not clinically 
significant, and abnormal clinically significant interpretations will be presented. 
12.7.4 
Shedding of Replication-deficient Vector 
Data will be summarized by count and percent positive by time point, along with median copy 
number.   
12.7.5 
Laboratory-confirmed Adenovirus Infection 
Viral culture results will be listed. 
12.8 Immunogenicity Analyses 
Immunology analyses will be conducted using the ITT and PP Populations with primary 
conclusions drawn from the PP Population. Analyses based on the ITT Population will be 
undertaken and presented only if >5% of subjects in any 1 dose group were excluded from the 
PP Population. No imputation for missing data will be performed. Data will be transformed as 
appropriate prior to analysis. 
Baseline is defined as the sample collected prior to IP administration on Day 1. 
12.8.1 
Secondary Endpoints (Humoral Immune Response) 
The primary variable of interest for assessment of humoral immune response to the NasoVAX 
antigen is homologous HAI antibody titer. The following HAI immunogenicity measures and 
their 95% CIs will be summarized by dose group:   
• 
GMT at baseline and postvaccination on Days 4, 8, 15, 29, 91, and 181 
• 
GMR on Days 4, 8, 15, 29, 91, and 181 (analysis of GMR will be performed using 
analysis of covariance [ANCOVA] with baseline titer as a covariate) 
• 
SPR on Days 4, 8, 15, 29, 91, and 181 
• 
SCR on Days 4, 8, 15, 29, 91, and 181 

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12.8.2 
Exploratory Endpoints 
Humoral Immune Response 
Humoral immune response (antibody level measured by microneutralization in serum) will be 
summarized by GMT at baseline and postvaccination on Day 29 and responder rate (the 
proportion of subjects with 2-fold and 4-fold rise since baseline) (95% CI) on Day 29. 
Cellular Immune Response  
Cellular responses (ELISpot SFUs to influenza HA peptides) will be summarized by geometric 
mean at baseline and postvaccination on Day 8 and responder rate on Day 8. 
Mucosal Immune Response  
Mucosal responses (IgA to influenza HA peptides by ELISA) will be summarized by geometric 
mean at baseline and postvaccination on Day 29 and responder rate on Day 29. 
Humoral Immune Response to Nonrepresented Influenza Strains 
Humoral immune response to nonrepresented influenza strain antigens (antibody level measured 
by HAI and microneutralization in serum) against each strain tested will be summarized by GMT 
at baseline and postvaccination on Day 29; GMR postvaccination on Day 29; and responder rate 
(the proportion of subjects with 2-fold and 4-fold rise since baseline) on Day 29. 
Effect of Predose Adenovirus Serotype 5 Serum Antibody Levels on Immunogenicity  
For the effect of predose Ad5 serum antibody levels on immunogenicity of NasoVAX on Day 
29, analysis will be performed using ANCOVA, with baseline Ad5 titer as a covariate. 
Comparison to Licensed Seasonal Influenza Vaccine  
Immunogenicity results from samples collected in this study will be compared to those from 
banked samples from a previous study of licensed seasonal vaccine in a similar subject 
population using a 2-sample comparison of means or nonparametric tests as indicated. 
12.9 Sample Size and Power 
The sample size for this study was selected as adequate and reasonable for an initial review of 
the safety and immunogenicity profile of the NasoVAX at doses to be well tolerated by young 
adults, rather than for statistical power. The sample size will permit initial estimates of 
reactogenicity. Given a total of 45 subjects receiving NasoVAX, the study will have an 80% 
probability of detecting at least 1 AE which occurs at a rate of 3.6%. If no SAEs are observed 
among the 45 subjects who receive NasoVAX, an approximation to the 1-sided upper bound of 
the 90% CI on the rate of SAE occurrence would be 5%. 

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12.10 Interim and Final Analyses 
One interim analysis of humoral immunogenicity data and safety data (including summaries of 
AE, reactogenicity, concomitant medications and vaccines, vital signs, ECG, and laboratory data 
and listing of any viral culture results) will be conducted when all data through the Day 29 visit 
are available, monitored, and confirmed by the Investigator for all subjects. The purpose of this 
review is to plan future studies and adjust the clinical development plan accordingly.  
An unblinded team composed only of members not otherwise involved in the study, will perform 
the interim analysis. All other study personnel including Investigators and investigational site 
staff and Sponsor staff and contractors will remain blinded to individual treatment assignments 
until database lock for final analysis. 
Safety and immunogenicity analyses from the interim review may be presented in an interim 
statistical report drafted by the Sponsor. Data therein will be used to support development and 
planning of future studies, and may be submitted to the Center for Biologics Evaluation and 
Research and other Regulatory Authorities as needed. 
The final CSR will include all study data through the end of study.  

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13 ETHICAL, LEGAL, AND ADMINISTRATIVE ISSUES  
The procedures set out in this study protocol, pertaining to the conduct, evaluation, and 
documentation of this study, are designed to ensure that the Sponsor and the Investigator abide 
by Good Clinical Practice (GCP) as described in International Council for Harmonisation (ICH) 
Guideline E6 and with all relevant laws. Compliance with these regulations also constitutes 
compliance with the ethical principles that have their origins in the Declaration of Helsinki. 
13.1 Institutional Review Board Approval 
The protocol, the ICF, any advertisement, or any other written information provided to the 
subject will be reviewed and approved by the Institutional Review Board (IRB). The Sponsor 
will supply relevant material for the Investigator to submit to the IRB for the study’s review and 
approval.   
The IRB will be informed of amendments to the study protocol, ICF, advertisement, or written 
information provided to the subject. Such amendments may not be implemented until approval 
by the IRB except when necessary to eliminate immediate hazards to the subjects. 
The IRB will be provided with reports at the interval required (not to exceed 1 year) and a report 
after the completion or discontinuation of the Investigator’s participation in the study. 
13.2 Informed Consent 
The Investigator (or designee) will explain the nature of the study to each subject. The subjects 
will be informed that participation is voluntary and that they can withdraw from the study at any 
time. After the study has been fully explained, each subject will provide written informed 
consent to study participation. The informed consent process will be documented by the use of a 
written ICF approved by the IRB and signed by the subject before protocol-specific procedures 
are performed. 
A copy of the ICF will be given to the subject, and the original ICF will be maintained with the 
subject’s study records. 
13.3 Biological Samples 
Biological samples collected for this study will become the property of the Sponsor and may be 
used for future research conducted by or on behalf of the Sponsor or its affiliates, partners, or 
collaborators. No identifiable personal information will be associated with these blood samples. 
Any samples remaining 15 years after the end of the study will be destroyed.  
Subjects who provide informed consent for the study will be informed that any residual samples 
may be retained for as yet undetermined additional testing. These tests may include human 
leukocyte antigen typing of the PBMC samples. Subjects will be asked explicitly to consent for 
such sample retention and potential future genetic research on their blood samples. 
A subject who is unwilling to have blood samples stored for future use can consent to participate 
in this study without having blood samples stored for future testing. In this case, the subject’s 
blood samples will be destroyed after all the tests specified for this study have been concluded. 

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A subject can withdraw consent for sample retention at any time, in which case the samples will 
be destroyed and no further testing will take place. To initiate the sample destruction process, the 
Investigator must notify the Sponsor about the withdrawal of consent for the storage of samples 
for future use and request sample destruction. 
13.4 Confidentiality 
Personal study subject data collected and processed for the purposes of this study will be 
managed by the Investigator and the investigational site staff with adequate precautions to ensure 
the confidentiality of these data, and in accordance with applicable laws and regulations on 
personal data protection. Each subject’s identity and personal data will remain confidential in the 
CSR, any presentation of the results of this study at meetings, or any publication. 
13.5 Protocol Compliance 
The Investigator should conduct the trial in compliance with the approved protocol. The 
Investigator must not make any changes to the study without Sponsor and IRB approval except 
when necessary to eliminate apparent immediate hazards to the subjects. A protocol change 
intended to eliminate an apparent immediate hazard to subjects may be implemented 
immediately, but the change must then be documented in an amendment, reported to the IRB 
within 3 working days, and submitted to the appropriate Regulatory Authority in the required 
time frame. The Investigator is responsible for abiding by the IRB’s rules and regulations for 
reporting protocol deviations. A Protocol Deviation Log will be created by the Investigator, and 
the Investigator will document and explain any deviation from the approved protocol on this log. 
The Protocol Deviation Log will be maintained in the study file. 
13.6 Protocol Amendments 
Any significant change in the study requires a protocol amendment. All protocol amendments 
must be reviewed and approved by the Sponsor, the Investigator, and the IRB before 
implementation. 
13.7 Publication and Disclosure Policy 
All information provided regarding the study, as well as all information collected or documented 
during the course of the study, will be regarded as confidential. The Investigator agrees not to 
disclose such information in any way without prior written permission from the Sponsor. 
The publication and disclosure policy will be addressed in a separate clinical trial agreement. 
13.8 Clinical Study Report 
A final CSR will be prepared in accordance with the ICH guideline on structure and contents of 
CSRs and any applicable regulatory and legal requirements. 
13.9 Financing and Insurance 
Financing and insurance will be addressed in a separate clinical trial agreement. 

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14 STUDY DATA AND RECORDS 
14.1 Direct Access 
The Investigator will grant direct access to the monitors, auditors, and other authorized 
representatives of the Sponsor; the IRB approving this research; and any applicable Regulatory 
Authorities to the study subjects’ original medical records for verification of clinical trial 
conduct and data. 
14.2 Source Documents 
Source documents are defined as the original documents (or certified copies) of clinical findings, 
observations, or other activities in a clinical trial necessary for the reconstruction and evaluation 
of the trial. All source documents produced in this study will be maintained by the Investigator 
and made available to the Sponsor’s representatives, the IRB, and any applicable Regulatory 
Authorities. 
14.3 Case Report Forms  
An electronic case report form (eCRF) will be used to record all subject data specified by this 
protocol into an electronic data capture (EDC) system. It is the responsibility of the Investigator 
to ensure the subject data are entered in an accurate and timely manner.  
14.4 Study Monitoring 
Before the start of the study, the Sponsor’s monitor will meet with the Investigator and 
appropriate investigational site staff for training on the protocol requirements and procedures. 
Throughout the course of the study, the Sponsor’s monitor will conduct site visits to verify that 
the rights and well-being of the subjects are protected; the reported trial data are accurate, 
complete, and verifiable from source documents; and that the conduct of the trial is in 
compliance with the currently approved protocol, GCP, and applicable regulatory and legal 
requirements. An unblinded monitor will also visit the site to review IP accountability. 
14.5 Data Management 
The study data will be using an EDC system. The Investigator and study site staff will receive 
system training and support. All protocol-required information collected during the study must 
be entered by the Investigator or designated representative in the eCRF. All data entries, 
modifications, or deletions will be recorded automatically in an electronic audit trail indicating 
the individual subject, original value, new value, reason for change, who made the change, and 
when the change was made. All data changes will be clearly indicated with a means to locate 
prior values. The system will be secured to prevent unauthorized access to the data or the system. 
This security will include the requirement for a user ID and password to enter or change data. 
The Investigator will maintain a list of individuals who are authorized to enter or correct data and 
their user IDs. 

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All electronic data entered by the site (including an electronic audit trail) as well as computer 
software (for accessing the data) will be maintained or made available at the site in compliance 
with applicable record retention regulations. The computerized system will be able to generate 
accurate and complete copies of records in both human-readable and electronic form for 
inspection, review, and copying by Regulatory Authorities, the IRB, or an auditor authorized by 
the Sponsor. Site documentation will identify the software systems used to create, modify, 
maintain, archive, retrieve, or transmit data. 
After review of the data in the eCRF, the Investigator or designated Subinvestigator will confirm 
the validity of each subject’s data. 
14.6 Retention of Records 
ICH-GCP requires that documents be retained until at least 2 years after the last approval of a 
marketing application in an ICH region and there are no pending or contemplated marketing 
applications in an ICH region or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the study drug. Study records will be maintained in 
accordance with these requirements and any applicable laws.  
No study records will be destroyed without prior authorization from the Sponsor. 

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15 REFERENCES 
Adenoviruses. Centers for Disease Control and Prevention Web site. 
https://www.cdc.gov/adenovirus/about/symptoms.html. Updated April 20, 2015. Accessed June 
9, 2017. 
Centers for Disease Control and Prevention. Estimates of deaths associated with seasonal 
influenza—United States, 1976-2007. MMWR Morb Mortal Wkly Rep. 2010;59(33):1057–62. 
Centers for Disease Control and Prevention. Prevention and Control of Seasonal Influenza with 
Vaccines Recommendations of the Advisory Committee on Immunization Practices — United 
States, 2016–17 Influenza Season. MMWR Morb Mortal Wkly Rep. 2016:65(5):1–52. 
Food and Drug Administration. Guidance for industry: Clinical data needed to support the 
licensure of seasonal inactivated influenza vaccines. Rockville, MD: U.S. Department of Health 
and Human Services; 2007a. Available at: 
http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInform
ation/Guidances/Vaccines/ucm091977.pdf. Accessed June 9, 2017. 
Food and Drug Administration. Guidance for industry: Toxicity grading scale for healthy adult 
and adolescent volunteers enrolled in preventive vaccine clinical trials. Rockville, MD: U.S. 
Department of Health and Human Services; 2007b. Available at: 
http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInform
ation/Guidances/Vaccines/ucm091977.pdf. Accessed June 9, 2017. 
Molinari NA, Ortega-Sanchez IR, Messonnier ML, et al. The annual impact of seasonal 
influenza in the US: Measuring disease burden and costs. Vaccine. 2007;25:5086–96.  
Seasonal Influenza Vaccine Effectiveness, 2005-2016. Centers for Disease Control and 
Prevention Web site. https://www.cdc.gov/flu/professionals/vaccination/effectiveness-
studies.htm. Updated October 14, 2016. Accessed June 9, 2017. 
Van Kampen KR, Shi Z, Gao P, et al. Safety and immunogenicity of adenovirus-vectored nasal 
and epicutaneous influenza vaccines in humans. Vaccine. 2005;23:1029–36. 
World Health Organization. Media centre: Influenza (seasonal). 
http://www.who.int/mediacentre/factsheets/fs211/en/. Updated November 2016. Accessed June 
9, 2017. 
Yang Y, Nunes FA, Berencsi K, et al. Cellular immunity to viral antigens limits E1 deleted 
adenoviruses for gene therapy. Proc Natl Acad Sci USA, 1994;91:4407–4411. 
Zimmerman RK, Nowalk MP, Chung J, et al. 2014-2015 influenza vaccine effectiveness in the 
United States by vaccine type. Clin Infect Dis. 2016;63:1564–1573.  

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16 APPENDICES

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Appendix 1 
Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive 
Vaccine Clinical Trials  
Vital Signs  
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life-threatening 
(Grade 4) 
Fever (°C)  
           (°F)  
38.0 – 38.4 
100.4 – 101.1 
38.5 – 38.9 
101.2 – 102.0 
39.0 – 40 
102.1 – 104 
> 40 
> 104 
Tachycardia - beats per minute 
101 – 115 
116 – 130 
> 130 
ER visit or hospitalization for 
arrhythmia 
Bradycardia - beats per minute 
50 – 54 
45 – 49 
< 45 
ER visit or hospitalization for 
arrhythmia 
Hypertension (systolic) - mm Hg 
141 – 150 
151 – 155 
> 155 
ER visit or hospitalization for 
malignant hypertension 
Hypertension (diastolic) - mm Hg 
91 – 95 
96 – 100 
> 100 
ER visit or hospitalization for 
malignant hypertension 
Hypotension (systolic) – mm Hg 
85 – 89 
80 – 84 
< 80 
ER visit or hospitalization for 
hypotensive shock 
Respiratory rate – breaths per minute 
17 – 20 
21 – 25 
> 25 
Intubation 
 
Systemic 
(General) 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life-threatening 
(Grade 4) 
Nausea/vomiting 
No interference with 
activity or 1 - 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 
2 - 3 loose stools or < 400 
gms/24 hours 
4 - 5 stools or 400 - 800 
gms/24 hours 
6 or more watery stools or > 
800 gms/24 hours or requires 
outpatient IV hydration 
ER visit or hospitalization 
Headache 
No interference with 
activity 
Repeated use of non-
narcotic pain reliever > 24 
hours or some interference 
with activity 
Significant; any use of 
narcotic pain reliever or 
prevents daily activity 
ER visit or hospitalization 
Fatigue 
No interference with 
activity 
Some interference with 
activity 
Significant; prevents daily 
activity 
ER visit or hospitalization 
Myalgia 
No interference with 
activity 
Some interference with 
activity 
Significant; prevents daily 
activity 
ER visit or hospitalization 
 

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Systemic Illness 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life-threatening 
(Grade 4) 
Illness or clinical adverse event (as 
defined according to applicable 
regulations) 
No interference with 
activity 
Some interference with 
activity not requiring medical 
intervention 
Prevents daily activity and 
requires medical intervention 
ER visit or hospitalization 
 
Serum Laboratory Abnormalities 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life-threatening 
(Grade 4) 
Sodium – hyponatremia mEq/L 
132 – 134 
130 – 131 
125 – 129 
< 125 
Sodium – hypernatremia mEq/L 
144 – 145 
146 – 147 
148 – 150 
> 150 
Potassium – hyperkalemia mEq/L 
5.1 – 5.2 
5.3 – 5.4 
5.5 – 5.6 
> 5.6 
Potassium – hypokalemia mEq/L 
3.5 – 3.6 
3.3 – 3.4 
3.1 – 3.2 
< 3.1 
Glucose – hypoglycemia mg/dL 
65 – 69 
55 – 64 
45 – 54 
< 45 
Glucose – hyperglycemia 
Fasting – mg/dL 
Random – mg/dL 
 
100 – 110 
110 – 125 
 
111 – 125 
126 – 200 
 
>125 
>200 
Insulin requirements or 
hyperosmolar coma 
Blood urea nitrogen 
BUN mg/dL 
23 – 26 
27 – 31 
> 31 
Requires dialysis 
Creatinine – mg/dL 
1.5 – 1.7 
1.8 – 2.0 
2.1 – 2.5 
> 2.5 or requires dialysis 
Calcium – hypocalcemia mg/dL 
8.0 – 8.4 
7.5 – 7.9 
7.0 – 7.4 
< 7.0 
Calcium – hypercalcemia mg/dL 
10.5 – 11.0 
11.1 – 11.5 
11.6 – 12.0 
> 12.0 
Magnesium – hypomagnesemia mg/dL 
1.3 – 1.5 
1.1 – 1.2 
0.9 – 1.0 
< 0.9 
Phosphorus – hypophosphatemia mg/dL 
2.3 – 2.5 
2.0 – 2.2 
1.6 – 1.9 
< 1.6 
CPK – mg/dL 
1.25 – 1.5 x ULN 
1.6 – 3.0 x ULN 
3.1 – 10 x ULN 
> 10 x ULN 
Albumin – hypoalbuminemia g/dL 
2.8 – 3.1 
2.5 – 2.7 
< 2.5 
-- 
Total Protein – hypoproteinemia g/dL 
5.5 – 6.0 
5.0 – 5.4 
< 5.0 
-- 
Alkaline phosphate – increase by factor 
1.1 – 2.0 x ULN 
2.1 – 3.0 x ULN 
3.1 – 10 x ULN 
> 10 x ULN 
Liver Function Tests – ALT, AST increase 
by factor 
1.1 – 2.5 x ULN 
2.6 – 5.0 x ULN 
5.1 – 10 x ULN 
> 10 x ULN 
Bilirubin – when accompanied by any 
increase in liver function test increase by 
factor 
1.1 – 1.25 x ULN 
1.26 – 1.5 x ULN 
1.51 – 1.75 x ULN 
> 1.75 x ULN 
Bilirubin – when liver function test is 
normal; increase by factor 
1.1 – 1.5 x ULN 
1.6 – 2.0 x ULN 
2.0 – 3.0 x ULN 
> 3.0 x ULN 
Cholesterol 
201 – 210 
211 – 225 
> 226 
--- 
Pancreatic enzymes – amylase, lipase 
1.1 – 1.5 x ULN 
1.6 – 2.0 x ULN 
2.1 – 5.0 x ULN 
> 5.0 x ULN 

Altimmune, Inc. 
 
ALT-103-201 
Protocol 
 
Version 4.0 
 
05 October 2017 
Confidential 
 
Page 58 of 66 
 
Hematology Laboratory Abnormalities 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life-threatening 
(Grade 4) 
Hemoglobin (female) - gm/dL 
11.0 – 12.0 
9.5 – 10.9 
8.0 – 9.4 
< 8.0 
Hemoglobin (female) change from 
baseline value - gm/dL 
Any decrease – 1.5 
1.6 – 2.0 
2.1 – 5.0 
> 5.0 
Hemoglobin (male) - gm/dL 
12.5 – 13.5 
10.5 – 12.4 
8.5 – 10.4 
< 8.5 
Hemoglobin (male) change from baseline 
value – gm/dL 
Any decrease – 1.5 
1.6 – 2.0 
2.1 – 5.0 
> 5.0 
WBC increase - cell/mm3 
10,800 – 15,000 
15,001 – 20,000 
20,001 – 25,000 
> 25,000 
WBC decrease - cell/mm3 
2,500 – 3,500 
1,500 – 2,499 
1,000 – 1,499 
< 1,000 
Lymphocytes decrease - cell/mm3 
750 – 1,000 
500 – 749 
250 – 499 
< 250 
Neutrophils decrease - cell/mm3 
1,500 – 2,000 
1,000 – 1,499 
500 – 999 
< 500 
Eosinophils - cell/mm3 
650 – 1500 
1501 - 5000 
> 5000 
Hypereosinophilic 
Platelets decreased - cell/mm3 
125,000 – 140,000 
100,000 – 124,000 
25,000 – 99,000 
< 25,000 
PT – increase by factor (prothrombin time) 
1.0 – 1.10 x ULN 
 1.11 – 1.20 x ULN 
1.21 – 1.25 x ULN 
> 1.25 ULN 
PTT – increase by factor (partial 
thromboplastin time) 
1.0 – 1.2 x ULN 
1.21 – 1.4 x ULN 
1.41 – 1.5 x ULN 
> 1.5 x ULN 
Fibrinogen increase - mg/dL 
400 – 500 
501 – 600 
> 600 
-- 
Fibrinogen decrease - mg/dL 
150 – 200 
125 – 149 
100 – 124 
< 100 or associated with gross 
bleeding or disseminated 
intravascular coagulation 
(DIC) 
 
Urine Laboratory Abnormalities 
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 (rbc/hpf) 
1 - 10 
11 - 50 
> 50 and/or gross blood 
Hospitalization or packed red 
blood cells (PRBC) 
transfusion 
 
 

Altimmune, Inc. 
 
ALT-103-201 
Protocol 
 
Version 4.0 
 
05 October 2017 
Confidential 
 
Page 59 of 66 
Appendix 2 
Sample Subject Diary 
 
 
 
 
 
PROTOCOL NUMBER:  ALT-103-201 
 
Single-ascending-dose Study of the Safety and Immunogenicity of 
NasoVAX 
 
SUBJECT DIARY 
 
Dispensed Date ________________ 
 
Influenza Vaccine, Intranasal (NasoVAX) 
SITE NUMBER: _____ _____  
 
SUBJECT NUMBER:  _____ _____ _____ _____- _____ _____ _____   SUBJECT INITIALS:  _____ _____ _____ 

Altimmune, Inc. 
 
ALT-103-201 
Protocol 
 
Version 4.0 
 
05 October 2017 
Confidential 
 
Page 60 of 66 
SUBJECT DIARY 
DIARY INSTRUCTION 
This diary is for you to use to record body temperature and other reactions, beginning after you receive the study 
vaccination.  Please complete the diary card (using indelible ink only) and bring it at each visit. 
 
• Please complete the diary at about the same time every day (after 4 PM) 
• Enter date in the following format:  MM/DD/YYYY 
• Take your temperature (thermometer in your mouth) and record it in Fahrenheit 
• Use the Severity Rating Guideline provided on page 5 to rate and evaluate severity scale of 
each  
symptom on the diary from 0-4 (Check ONLY one option).  If you have questions about any of 
these  
ratings, please ask the study team.  
• Check ‘Yes’ or ‘No’ for medication/treatment taken for symptoms and the study nurse will 
collect  
details at your next visit 
Also be prepared to discuss any other health issues you may experience 
with the study nurse at each visit. 
 
If you develop serious symptoms, have a significant illness 
or injury with emergency room or hospital care during 
the research study, please contact: 
Clinical site phone number:  ___ ___ ___ - ___ ___ ___ - ___ ___ ___ ___ 
If you need to be seen immediately by a physician, please contact your primary-care physician 
or visit your nearest emergency room as soon as possible. 

Altimmune, Inc. 
 
ALT-103-201 
Protocol 
 
Version 4.0 
 
05 October 2017 
Confidential 
 
Page 61 of 66 
 
DAY 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
DATE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TEMP (OF) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Headache 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
Fatigue 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
Muscle 
Ache 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
Nausea 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
Vomiting 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
Diarrhea 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 

Altimmune, Inc. 
 
ALT-103-201 
Protocol 
 
Version 4.0 
 
05 October 2017 
Confidential 
 
Page 62 of 66 
DAY 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
Chills 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
Nasal 
Irritation 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
Sneezing 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
Nasal 
Congestion 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
Cough 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
Sore 
Throat 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
Change 
In Smell 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
Change 
In Taste 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 

Altimmune, Inc. 
 
ALT-103-201 
Protocol 
 
Version 4.0 
 
05 October 2017 
Confidential 
 
Page 63 of 66 
DAY 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
Change 
In Vision 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
Eye Pain 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
 = 0 
 = 1 
 = 2 
 = 3 
 = 4 
Medication 
or 
Treatment 
Taken? 
 = 
Yes 
 
 = 
No 
 = 
Yes 
 
 = 
No 
 = 
Yes 
 
 = 
No 
 = 
Yes 
 
 = 
No 
 = 
Yes 
 
 = 
No 
 = 
Yes 
 
 = 
No 
 = 
Yes 
 
 = 
No 
 = 
Yes 
 
 = 
No 
 = 
Yes 
 
 = 
No 
 = 
Yes 
 
 = 
No 
 = 
Yes 
 
 = 
No 
 = 
Yes 
 
 = 
No 
 = 
Yes 
 
 = 
No 
 = 
Yes 
 
 = 
No 
 
SEVERITY RATING GUIDELINE 
Grade 
0 
1 
(Mild) 
2 
(Moderate) 
3 
(Severe) 
4 
(Potentially Life 
Threatening) 
Headache 
None 
No interference with daily 
activity 
Interferes with daily activity or 
bad enough to take non-narcotic 
medicine 
Prevents daily activity or required 
narcotic pain medicine 
So bad that required ER visit or 
hospitalization 
Fatigue 
None 
No interference with daily 
activity 
Some interference with daily 
activity 
Prevents daily activity 
So bad that required ER visit or 
hospitalization 
Muscle 
Ache 
None 
No interference with daily 
activity 
Some interference with daily 
activity 
Prevents daily activity 
So bad that required ER visit or 
hospitalization 
Nausea 
None 
No interference with daily 
activity 
Some interference with daily 
activity 
Prevents daily activity 
So bad that required ER visit or 
hospitalization 
Vomiting 
None 
1-2 episodes past 24h OR No 
interference with daily activity 
More than 2 episodes OR Some 
interference with daily activity 
Prevents daily activity OR 
Requires outpatient IV hydration 
So bad that required ER visit or 
hospitalization 
Diarrhea 
None 
2-3 loose stools past 24 h 
4-5 stools past 24h 
6 or more stools past 24h OR 
outpatient IV hydration 
So bad that required ER visit or 
hospitalization 
Chills 
None 
Felt cold, mild shivering 
Shaking chills 1-2 episodes 
3 or more episodes of shaking 
chills 
So bad that required ER visit or 
hospitalization 

Altimmune, Inc. 
 
ALT-103-201 
Protocol 
 
Version 4.0 
 
05 October 2017 
Confidential 
 
Page 64 of 66 
Nasal 
Irritation 
None 
Not interfering with daily activity 
Bothersome enough to interfere 
with daily activity or treated with 
medication 
Severe enough to prevent daily 
activity 
So bad that required ER visit or 
hospitalization 
Sneezing 
None 
Not interfering with daily activity 
Bothersome enough to interfere 
with daily activity or treated with 
medication 
Severe enough to prevent daily 
activity 
So bad that required ER visit or 
hospitalization 
Nasal 
Congestion 
None 
Not interfering with daily activity 
Bothersome enough to interfere 
with daily activity or treated with 
medication 
Severe enough to prevent daily 
activity 
So bad that required ER visit or 
hospitalization 
Cough 
None 
Not interfering with daily activity 
Bothersome enough to interfere 
with daily activity or treated with 
medication 
Severe enough to prevent daily 
activity or interfere with 
breathing or eating 
So bad that required ER visit or 
hospitalization 
Sore 
Throat 
None 
Not interfering with daily activity 
interferes with eating or other 
daily activity OR requires 
medication 
Prevents daily activity OR 
requires narcotic medication  
So bad that required ER visit or 
hospitalization 
Change in 
Smell 
None 
Not interfering with daily activity 
Bothersome enough to interfere 
with daily activity or treated with 
medication 
Unable to distinguish odors even 
after decongestant medication 
So bad that required ER visit or 
hospitalization 
Change in 
Taste 
None 
Not interfering with daily activity 
Affects enjoyment of meals or 
other interference with daily 
activity 
Prevents ability to eat 
So bad that required ER visit or 
hospitalization 
Change in 
Vision 
None 
Brief episode of mild blurring, 
floaters etc. that does not interfere 
with activity 
Sustained visual disturbance or 
interference with daily activity 
Loss of vision even if transient or 
visual symptoms that prevent 
daily activity 
So bad that required ER visit or 
hospitalization 
Eye Pain 
None 
No interference with daily 
activity 
Interferes with daily activity or 
bad enough to take non-narcotic 
medicine 
Prevents daily activity or required 
narcotic pain medicine 
So bad that required ER visit or 
hospitalization 
 

Altimmune, Inc. 
ALT-103-201 
Protocol 
Version 4.0 
05 October 2017 
Confidential 
Page 65 of 66 
Appendix 3 
Immunosuppressive Medications 
Corticosteroids 
• 
prednisone (Deltasone, Orasone) 
• 
budesonide (Entocort EC) 
• 
prednisolone (Millipred) 
Calcineurin inhibitors 
• 
cyclosporine (Neoral, Sandimmune, SangCya) 
• 
tacrolimus (Astagraf XL, Envarsus XR, Prograf) 
Mechanistic target of rapamycin (mTOR) inhibitors 
• 
sirolimus (Rapamune) 
• 
everolimus (Afinitor, Zortress) 
Inosine monophosphate dehydrogenase (IMDH) inhibitors 
• 
azathioprine (Azasan, Imuran) 
• 
leflunomide (Arava) 
• 
mycophenolate (CellCept, Myfortic) 
Biologics 
• 
abatacept (Orencia) 
• 
adalimumab (Humira) 
• 
anakinra (Kineret) 
• 
certolizumab (Cimzia) 
• 
etanercept (Enbrel) 
• 
golimumab (Simponi) 
• 
infliximab (Remicade) 
• 
ixekizumab (Taltz) 
• 
natalizumab (Tysabri) 
• 
rituximab (Rituxan) 
• 
secukinumab (Cosentyx) 
• 
tocilizumab (Actemra) 
• 
ustekinumab (Stelara) 
• 
vedolizumab (Entyvio) 
Monoclonal antibodies 
• 
basiliximab (Simulect) 
• 
daclizumab (Zinbryta) 
• 
muromonab (Orthoclone OKT3) 

Altimmune, Inc. 
ALT-103-201 
Protocol 
Version 4.0 
05 October 2017 
Confidential 
Page 66 of 66 
Appendix 4 
Protocol Amendments: Summary of Changes   
The first version of this Clinical Trial Protocol implemented was Version 3.0 Amendment 2 
(31 July 2017). Significant changes (changes other than clerical changes) after this version are 
summarized below. 
Amendment 3 (Version 4.0, 05 October 2017) 
Section(s) 
Change  
Rationale 
1.1, 4.1, 7.3, 8.2.1, Appendix 2 
Change to diary format and addition of 
collection of data on medication and 
treatment 
FDA request 
1.1, 4.1 
Addition: “At each visit, the subject 
will also be asked about the interim 
medical history and use of any 
medications.” 
Clarity 
5.2 
Clarification of Exclusion Criterion 27 
Clarity 
6.4, 12.10 
Clarification that individual treatment 
assignments will remain blinded 
Clarity 
6.9 
Addition of salpingectomy and 
oophorectomy as acceptable 
contraception methods as stated in 
inclusion criteria 
Consistency 
7.3 
Exclusion of temperature as item 
graded by the subject in the diary 
Clarity 
11.2 
Clarification of study termination 
procedure for subject discontinuing on 
Day 29 
Clarity 
12.10 
Addition of requirement for 
Investigator confirmation of data for 
interim analysis dataset 
Completeness