A Randomized, Partially-Blinded, Active Comparator-Controlled, Dose-Ranging, Safety, Tolerability, and Immunogenicity Phase 1/2 Study of an Adjuvanted Seasonal Recombinant Quadrivalent VLP Influenza Vaccine in Adults 65 Years of Age and Older
Phase: PHASE1
Conditions: Influenza
Sponsor: Medicago

 
 
Confidential Information 
Information in this protocol is confidential and should not be disclosed, other than to those directly involved in the 
execution or the ethical review of the study, without written authorization from Medicago USA Inc. (herein after 
known as “Medicago”), and its affiliates. This study will be conducted in accordance with applicable Good Clinical 
Practice (GCP) guidelines, the United States Code of Federal Regulations (CFR), and International Conference on 
Harmonization (ICH) guidelines. 
 
 
Clinical Protocol 
A Randomized, Partially-Blinded, Active Comparator-Controlled, Dose-Ranging, Safety, 
Tolerability, and Immunogenicity Phase 1/2 Study of an Adjuvanted Seasonal 
Recombinant Quadrivalent VLP Influenza Vaccine in Adults 65 Years of Age and Older 
 
CP-PRO-AdjQVLP-020; Phase 1/2 
 
Adjuvanted Recombinant Quadrivalent VLP Influenza Vaccine 
 
 
 
Name of Sponsor: 
Medicago USA Inc. 
7 Triangle Drive 
Durham (NC), United States 27713 
 
 
 
 
Status: 
Final version 5.0 
 
 
Date: 
23-Feb-2022 

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COORDINATING INVESTIGATOR SIGNATURE 
Study Title: 
A Randomized, Partially-Blinded, Active Comparator-Controlled, Dose-
Ranging, Safety, Tolerability, and Immunogenicity Phase 1/2 Study of an 
Adjuvanted Seasonal Recombinant Quadrivalent VLP Influenza Vaccine 
in Adults 65 Years of Age and Older 
 
I have read the version 5.0 (dated 23-Feb-2022) Protocol No. CP-PRO-AdjQVLP-020 titled, “A 
Randomized, Partially-Blinded, Active Comparator-Controlled, Dose-Ranging, Safety, 
Tolerability, and Immunogenicity Phase 1/2 Study of an Adjuvanted Seasonal Recombinant 
Quadrivalent VLP Influenza Vaccine in Adults 65 Years of Age and Older”. 
I have fully discussed the objectives of this study and the contents of this protocol with the 
Sponsor’s representative and I agree to accept the responsibility to act as Coordinating 
Investigator for this study. 
 
Coordinating Investigator: 
Name (typed or 
printed): 
 
Institution and 
Address: 
 
 
 
 
 
Telephone Number: 
 
 
 
Signature 
 
Date (YYYY-MM-DD) 
 
Note: If the address or the telephone number of the Investigator changes during the course of the 
study, written notification will be provided by the Investigator to the Sponsor, and a protocol 
amendment will not be required. 
 

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INVESTIGATOR AGREEMENT 
I have read the version 5.0 (dated 23-Feb-2022) Protocol No. CP-PRO-AdjQVLP-020 titled, “A 
Randomized, Partially-Blinded, Active Comparator-Controlled, Dose-Ranging, Safety, 
Tolerability, and Immunogenicity Phase 1/2 Study of an Adjuvanted Seasonal Recombinant 
Quadrivalent VLP Influenza Vaccine in Adults 65 Years of Age and Older”. 
I have fully discussed the objectives of this study and the contents of this protocol with the 
Sponsor’s representative. 
I understand that the information in this protocol is confidential and should not be disclosed, 
other than to those directly involved in the execution or the ethical review of the study, without 
prior written authorization from Medicago. It is, however, permissible to discuss information 
contained in this protocol with a subject in order to obtain consent once Institutional Review 
Board (IRB) approval is obtained. 
I agree to conduct this study according to this protocol and to comply with its requirements, 
subject to ethical and safety considerations and guidelines, and to conduct the study in 
accordance with International Conference on Harmonisation (ICH) guidelines, Good Clinical 
Practice (GCP), Investigational New Drug (IND) regulations, and other applicable regulatory 
requirements. 
I understand that the Sponsor may decide to suspend or prematurely terminate this study at any 
time for whatever reason and that such a decision will be communicated to me in writing. 
Conversely, should I decide to withdraw from execution of the study, I will communicate my 
intention immediately in writing to the Sponsor. 
Principal Investigator: 
Name (typed or 
printed): 
 
Institution and 
Address: 
 
 
 
 
 
Telephone Number: 
 
 
 
Signature 
 
Date (YYYY-MM-DD) 
 
Note: If the address or the telephone number of the Investigator changes during the course of 
the study, written notification will be provided by the Investigator to the Sponsor, and a 
protocol amendment will not be required. 
 

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TABLE OF CONTENTS 
SIGNATURES ................................................................................................................................ 2
COORDINATING INVESTIGATOR SIGNATURE .................................................................... 4
INVESTIGATOR AGREEMENT.................................................................................................. 5
TABLE OF CONTENTS ................................................................................................................ 6
LIST OF TABLES ........................................................................................................................ 11
SYNOPSIS .................................................................................................................................... 12
ABBREVIATIONS ...................................................................................................................... 23
1
INTRODUCTION ................................................................................................................. 25
1.1
Quadrivalent VLP Influenza Vaccine ............................................................................ 26
1.2
Pre-clinical Studies ......................................................................................................... 27
1.3
Clinical Studies .............................................................................................................. 27
1.3.1
Safety Overview for QVLP .................................................................................... 28
1.3.1.1
Safety Overview for AS03 .............................................................................. 30
1.3.2
Immunogenicity and Efficacy Overview for QVLP ............................................... 30
1.3.2.1
Immunogenicity and Efficacy Overview for AS03 ......................................... 31
1.4
Overall Rationale for the Study ...................................................................................... 31
2
OBJECTIVES ........................................................................................................................ 32
2.1
Primary Objectives ......................................................................................................... 32
2.2
Secondary Objectives ..................................................................................................... 32
3
STUDY ADMINISTRATIVE STRUCTURE ...................................................................... 33
4
STUDY DESIGN AND RATIONALE ................................................................................. 33
4.1
Overview of Study Design ............................................................................................. 33
4.2
Rationale of Study Design .............................................................................................. 34
4.2.1
Randomization ........................................................................................................ 34
4.2.2
Blinding................................................................................................................... 34
4.2.3
Dose Selection and Dosage Regimen ..................................................................... 35
4.2.4
Route of Administration ......................................................................................... 35
4.2.5
Active Comparators Selection ................................................................................ 35
4.2.6
Study Duration ........................................................................................................ 35
5
STUDY POPULATION ........................................................................................................ 36
5.1
Inclusion Criteria ............................................................................................................ 36

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5.2
Exclusion Criteria ........................................................................................................... 36
5.3
Prior and Concomitant Therapy ..................................................................................... 38
5.4
Prohibited Therapy ......................................................................................................... 39
6
TREATMENT ALLOCATION AND BLINDING .............................................................. 40
6.1
Randomization ............................................................................................................... 40
6.2
Blinding .......................................................................................................................... 40
7
DOSAGE AND ADMINISTRATION .................................................................................. 42
8
SPECIMENS AND CLINICAL SUPPLIES ......................................................................... 42
8.1
Management of Samples ................................................................................................ 42
8.2
Collection of Samples .................................................................................................... 42
8.3
Clinical Supplies ............................................................................................................ 42
9
TREATMENT COMPLIANCE ............................................................................................ 43
10
STUDY EVALUATIONS ..................................................................................................... 43
10.1
Study Procedures ............................................................................................................ 43
10.1.1
Overview ................................................................................................................. 43
10.1.2
General COVID-19 Precautions at Clinical Sites ................................................... 43
10.1.3
Screening (Visit 1) .................................................................................................. 44
10.1.4
Vaccination (Day 0) (Visit 2) ................................................................................. 45
10.1.4.1
Prior to Vaccination ......................................................................................... 45
10.1.4.2
Vaccination ...................................................................................................... 46
10.1.4.3
Thirty Minutes Post-vaccination ..................................................................... 46
10.1.5
Day 1 and Day 8 (Telephone Contact) ................................................................... 48
10.1.6
Day 3 Follow-up (Visit 3) ....................................................................................... 49
10.1.7
Day 28 (Visit 4) ...................................................................................................... 50
10.1.8
Monthly Calls Thereafter (Telephone Contact) ...................................................... 50
10.1.9
Day 182 (Visit 5) .................................................................................................... 51
10.1.10 Final Visit – Day 365 (Visit 6) ............................................................................... 51
10.2
Safety .............................................................................................................................. 52
10.2.1
Evaluations .............................................................................................................. 52
10.2.1.1
Solicited Local and Systemic AEs ................................................................... 52
10.2.1.2
Adverse Events ................................................................................................ 53
10.2.1.3
Clinical Laboratory Tests ................................................................................ 54

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10.2.1.4
Vital Signs ....................................................................................................... 55
10.2.1.5
Physical Examinations ..................................................................................... 55
10.2.2
Safety Endpoints ..................................................................................................... 55
10.2.2.1
Primary Endpoints ........................................................................................... 55
10.2.2.2
Secondary Endpoints ....................................................................................... 56
10.3
Immunogenicity ............................................................................................................. 57
10.3.1
Immunogenicity Evaluations .................................................................................. 57
10.3.2
Immunogenicity Endpoints ..................................................................................... 57
10.3.2.1
Primary Endpoint ............................................................................................. 57
10.3.2.2
Secondary Endpoints ....................................................................................... 57
11
SUBJECT COMPLETION/WITHDRAWAL ...................................................................... 59
11.1
Temporary Contraindications ......................................................................................... 59
11.2
Screening Failures .......................................................................................................... 59
11.3
Removal of Subjects from Treatment or Assessment .................................................... 59
11.3.1
Follow-up of Discontinuations ............................................................................... 60
11.3.2
Lost to Follow-up Procedures ................................................................................. 60
11.4
Interruption of the Study ................................................................................................ 60
12
STATISTICAL METHODS.................................................................................................. 61
12.1
Analysis Populations ...................................................................................................... 61
12.1.1
Safety Analysis Set ................................................................................................. 61
12.1.2
Intention-To-Treat Set ............................................................................................ 61
12.1.3
Per Protocol Set....................................................................................................... 61
12.2
Sample Size Determination ............................................................................................ 62
12.3
Day 28 and Day 182 Data Analyses ............................................................................... 62
12.4
Baseline and Subject Disposition ................................................................................... 62
12.5
Safety Analyses .............................................................................................................. 62
12.5.1
Analysis of Primary Endpoints ............................................................................... 62
12.5.2
Analysis of Secondary Endpoints ........................................................................... 63
12.6
Immunogenicity Analyses .............................................................................................. 64
12.6.1
Analysis of Primary Endpoint ................................................................................. 64
12.6.2
Analysis of Secondary Endpoints ........................................................................... 64
13
ADVERSE EVENT REPORTING ....................................................................................... 66

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13.1
Definitions ...................................................................................................................... 66
13.1.1
Serious Adverse Events .......................................................................................... 66
13.1.2
Adverse Events ....................................................................................................... 67
13.1.2.1
Medically Attended Adverse Events ............................................................... 68
13.1.3
Adverse Events of Special Interest ......................................................................... 68
13.1.3.1
Adverse Events of Special Interest for QVLP ................................................. 68
13.1.3.1.1
Hypersensitivity Reactions ......................................................................... 68
13.1.3.2
Adverse Events of Special Interest for AS03 .................................................. 69
13.1.3.2.1
Narcolepsy .................................................................................................. 69
13.1.3.2.2
Potential Immune-Mediated Diseases and Other AESI as Listed in Section 
19.5 
69
13.1.4
New Onset of Chronic Disease ............................................................................... 70
13.1.5
Expectedness of an Adverse Drug Reaction ........................................................... 70
13.1.6
Initial SAE Reporting by the Investigator .............................................................. 70
13.1.7
Follow-up Reporting by the Investigator ................................................................ 71
13.1.8
Reporting of SAEs Occurring after Surveillance Period or Study Termination ..... 71
13.1.9
Causal Relationship ................................................................................................ 71
13.1.10 Reporting of SAEs to Health Authorities and IRB ................................................. 72
13.1.11 Independent Data Monitoring Committee .............................................................. 72
13.1.12 Safety Review and Stopping Rules ......................................................................... 73
14
INVESTIGATIONAL PRODUCT INFORMATION .......................................................... 74
14.1
Identity of Investigational Product ................................................................................. 74
14.1.1
Study Vaccine Composition ................................................................................... 74
14.1.2
Active Comparators ................................................................................................ 75
14.1.3
Preparation and Administration of Study Vaccine ................................................. 75
14.1.4
Preparation, Handling, Storage, and Precautions for Use ....................................... 76
14.2
Packaging ....................................................................................................................... 76
14.3
Labeling .......................................................................................................................... 76
14.4
Drug Accountability ....................................................................................................... 77
15
STUDY-SPECIFIC MATERIALS ....................................................................................... 77
16
ETHICAL ASPECTS ............................................................................................................ 77
16.1
Study-Specific Design Considerations ........................................................................... 77

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16.2
Regulatory Ethics Compliance ....................................................................................... 78
16.2.1
Investigator Responsibilities ................................................................................... 78
16.2.2
Independent Ethics Committee or Institutional Review Board .............................. 78
16.2.3
Informed Consent.................................................................................................... 79
16.2.4
Privacy of Personal Data ......................................................................................... 79
17
ADMINISTRATIVE REQUIREMENTS ............................................................................. 80
17.1
Protocol Amendments .................................................................................................... 80
17.2
Regulatory Documentation ............................................................................................ 80
17.2.1
Regulatory Approval/Notification .......................................................................... 80
17.3
Source Documentation ................................................................................................... 80
17.3.1
Diary and Memory Aid ........................................................................................... 81
17.4
Case Report Form Completion ....................................................................................... 82
17.5
Quality Control (Study Monitoring) .............................................................................. 82
17.6
Quality Assurance .......................................................................................................... 82
17.7
Record Retention ............................................................................................................ 82
17.8
Study Completion/Termination ...................................................................................... 83
17.8.1
Study Completion ................................................................................................... 83
17.8.2
Study Termination .................................................................................................. 83
17.9
Registration of Clinical Studies and Disclosure of Results............................................ 84
17.10
Publication Policy ....................................................................................................... 84
18
REFERENCES ...................................................................................................................... 84
19
APPENDICES ....................................................................................................................... 89
19.1
Appendix 1 – Sample Ruler to Measure Local Adverse Events .................................... 89
19.2
Appendix 2 – Subject Diary Sample Pages .................................................................... 90
19.3
Appendix 3 – Subject Memory Aid Sample Pages ........................................................ 96
19.4
Appendix 4 – Seven-Day Safety Summary (Sample) .................................................. 100
19.5
Appendix 5 – List of Potential Immune-Mediated Diseases ........................................ 101
 

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LIST OF TABLES 
Table 1 Time and Events Schedule: General Information ............................................................ 21
Table 2 Summary of Design of Clinical Studies Performed to Date with QVLP ........................ 27
Table 3 Study Administrative Structure ....................................................................................... 33
Table 4 Study Treatment Groups .................................................................................................. 33
Table 5 Estimated Blood Volume Drawn ..................................................................................... 43
Table 6 Severity Grades for Solicited Local and Systemic AEs .................................................. 53
Table 7 Clinical Laboratory Tests................................................................................................. 54
 
 

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SYNOPSIS 
Sponsor: 
Medicago USA Inc. 
Investigational Product: 
Adjuvanted Recombinant Quadrivalent VLP Influenza Vaccine 
(QVLP) 
Active Substance(s): 
Mix of recombinant H1, H3, and two B hemagglutinin proteins 
expressed as virus-like particles (VLP) for the 2020-2021 
Northern Hemisphere influenza virus strains 
Adjuvant 
AS03 (produced by GlaxoSmithKline) 
Control Products: 
Active comparators:  
Fluzone® High-Dose Quadrivalent (produced by Sanofi Pasteur); 
2020-2021 Northern Hemisphere influenza virus strains1 
(Fluzone HD Quad) 
QVLP (unadjuvanted) for the 2020-2021 Northern Hemisphere 
influenza virus strains  
Protocol Title: 
A Randomized, Partially-Blinded, Active Comparator-
Controlled, Dose-Ranging, Safety, Tolerability, and 
Immunogenicity Phase 1/2 Study of an Adjuvanted Seasonal 
Recombinant Quadrivalent VLP Influenza Vaccine in Adults 
65 Years of Age and Older 
Protocol Number: 
CP-PRO-AdjQVLP-020 
Development Phase: 
Phase 1/2 
Study Center(s): 
The study will be conducted at multiple sites. 
Study Rationale: 
This Phase 1/2 study is to assess the safety, tolerability, and 
immunogenicity of adjuvanted recombinant QVLP in healthy 
adults 65 years of age and older. One dose of the following 
vaccine formulations will be administered in this study: 
x 30 μg/strain of QVLP adjuvanted with AS03, or  
x 30 μg/strain of QVLP unadjuvanted, or  
x Fluzone HD Quad. 
 
 
1 Fluzone® High-Dose Quadrivalent is licensed in the US and expected to be commercially available for the 2020-
2021 influenza season. 

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Planned Study Period: 
The total planned study period is approximately 17 months. 
Subject enrollment will continue for approximately 4 to 
5 months. Biological samples for immunogenicity assessments 
will be collected over 4 weeks post-vaccination, and long-term 
safety follow up and evaluation of durability of the immune 
responses will continue 6 and 12 months after administration of 
the vaccines. 
Study Objectives 
  Primary Objectives: 
The primary objectives of the study are: 
Safety: 
x To assess the safety and tolerability of a single dose of QVLP 
(30 μg/strain) with AS03 adjuvant compared to QVLP 
(30 μg/strain) (unadjuvanted) and Fluzone HD Quad; 
Immunogenicity: 
x To assess the immunogenicity of a single dose of QVLP 
(30 μg/strain) with AS03 adjuvant compared to QVLP 
(30 μg/strain) (unadjuvanted) and Fluzone HD Quad, as 
measured by hemagglutination inhibition (HI) assay against 
homologous influenza strains. 
  Secondary Objectives: 
The secondary objectives of this study are: 
Immunogenicity: 
x To assess the immunogenicity of a single dose of QVLP 
(30 μg/strain) with AS03 adjuvant compared to QVLP 
(30 μg/strain) (unadjuvanted) and Fluzone HD Quad, as 
measured by microneutralization (MN) assay against 
homologous influenza strains; 
x To assess the immunogenicity of a single dose of QVLP 
(30 μg/strain) with AS03 adjuvant compared to QVLP 
(30 μg/strain) (unadjuvanted) and Fluzone HD Quad, as 
measured by HI assay against heterologous influenza strains; 
x To assess the immunogenicity of a single dose of QVLP 
(30 μg/strain) with AS03 adjuvant compared to QVLP 
(30 μg/strain) (unadjuvanted) and Fluzone HD Quad, as 
measured by HI (homologous and heterologous influenza 
strains) and MN (homologous influenza strains) assays, 
stratified by prior influenza vaccination status, if >25% of the 
enrolled subjects have received a standard influenza vaccine 
during the 12 months prior to study vaccination;  
x To evaluate the persistence of antibody responses, as 
determined by HI titers against homologous influenza strains, 
at 6 and 12 months post-vaccination; 
Safety: 
x To assess the safety and tolerability of a single dose of QVLP 
(30 μg/strain) with AS03 adjuvant compared to QVLP 

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(30 μg/strain) (unadjuvanted) and Fluzone HD Quad, 
stratified by prior influenza vaccination status, if >25% of the 
enrolled subjects have received a standard influenza vaccine 
during the 12 months prior to study vaccination. 
Number of Planned 
Subjects: 
Approximately 120 healthy adult subjects 65 years of age and 
older are planned for randomization in a 1:1:1 ratio to receive 
QVLP at a dose of 30 μg/strain with AS03 adjuvant or QVLP 
(30 μg/strain) (unadjuvanted) or Fluzone HD Quad. 
Sample Size 
Determination: 
The sample size up to approximately 120 subjects with 
40 subjects in each treatment group will make it possible to 
perform the initial evaluation of vaccine immunogenicity and 
detect gross differences in rates of adverse events. The sample 
size is not large enough to detect all types of adverse reactions, 
including less frequent or rare events. The objective of this study 
is to quantify the type, percentage, duration, intensity, and 
relationship of common post-vaccination safety events to 
determine if they differ clinically among the treatment groups. 
Study Population: 
Healthy male and female subjects 65 years of age and older will 
be included in the study. 
Dosage and 
Administration: 
On Day 0, subjects will receive one intramuscular (IM) injection 
into the deltoid region of the non-dominant (if possible) arm, of 
their assigned treatment: 
x 30 μg/strain of QVLP adjuvanted with AS03, or  
x 30 μg/strain of QVLP unadjuvanted, or  
x Fluzone HD Quad. 
The volume of injection will be 0.7 mL for all treatments. 
Study Design: 
This is a randomized, partially-blinded, active comparator-
controlled, multicenter, Phase 1/2 dose-finding, safety, 
tolerability and immunogenicity study. 
The influenza strain composition of the vaccines used in this 
study will be based on the recommended World Health 
Organization (WHO) strains for vaccination in the 2020-2021 
season in the Northern Hemisphere. 
Approximately 120 healthy male and female subjects 65 years 
of age and older will be enrolled into three treatment groups: 
QVLP given at a dose level of 30 μg/strain with AS03 adjuvant 
or QVLP (30 μg/strain) (unadjuvanted) or Fluzone HD Quad.  

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Treatment 
Group  
Treatments 
Dose Level 
No. of 
Subjects 
1 
QVLP adjuvanted with AS03 
30 μg/strain 
40 
2 
QVLP unadjuvanted 
30 μg/strain 
40 
3 
Fluzone HD Quad 
60 μg/strain 
40 
The first 3 subjects per treatment group enrolled in the study 
will receive an IM injection of one of the three treatments listed 
in the table above. The vaccinations for the first three subjects in 
each treatment group will be staggered so that each vaccination 
must be performed at least 30 minutes apart. The seven-day 
safety data will be collected from these subjects and reviewed 
by the Independent Data Monitoring Committee (IDMC), prior 
to permitting the vaccination of the remaining subjects in these 
three treatment groups.  
Subjects will be screened up to seven days in advance of the 
vaccine administration and will demonstrate a satisfactory 
baseline medical assessment by medical history, general 
physical examination, urinalysis, haematological and blood 
biochemistry analyses, and serum screening for HIV, 
Hepatitis B and Hepatitis C markers. On Day 0, vaccine 
administration will occur. Phone contacts will be made one day 
and eight days after the vaccine administration, specifically for 
review of the subject’s safety and concomitant medication data. 
Visits to the Investigator site will occur 3 days after the vaccine 
administration (Day 3) for key safety assessments and 28 days 
after the vaccine administration (Day 28) for key safety and 
immunogenicity assessments. Subjects will have monthly 
telephone calls after Day 28 up to the end of the study. Subjects 
will return to the Investigator site on Day 182 for 
immunogenicity and safety assessments (6-month follow-up) 
and on Day 365 for final immunogenicity and safety 
assessments (12-month follow-up).  
Subjects enrolled and vaccinated in the QVLP (15 μg/strain and 
45 μg/strain) adjuvanted with AS03 adjuvant (full dose or half 
dose) and the QVLP (30 μg/strain) adjuvanted with AS03 
adjuvant (half dose) treatment groups will complete study 
procedures as outlined above and will be followed for safety and 
immunogenicity assessments up to Day 365. 
Blinding 
In this study, a partially-blinded design is applied whereby the 
following individuals will not have access to treatment 
allocation (i.e. remain “blind”) throughout the entire study 
duration: the subjects, the Investigators and all personnel 
involved in the clinical conduct of the study (except the staff 

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involved in the preparation and administration of the study 
vaccine, the quality assurance auditor, and quality control 
reviewers), Medicago clinical staff and medical staff involved in 
safety evaluations (e.g. causality assessments), and all personnel 
involved in sample analysis at the central and testing (HI and 
MN) laboratories.  
The IDMC and the independent statistician involved in the 
preparation of the safety data summary for the IDMC reviews 
will have access to or be aware of treatment allocation (i.e. be 
“unblinded”). The IDMC will review safety data and will make 
recommendations for the entire duration of the study. 
In addition, select personnel of the third-party statistical team 
will have access to treatment allocation (i.e. be “unblinded”) for 
the entire duration of the study since these personnel will be 
involved in the Day 28 data analysis and the Day 182 data 
analysis (see Statistical Methods section below). 
A small number of Medicago personnel will have access to the 
Day 28 and Day 182 data analyses (i.e. be “unblinded” to results 
and/or treatment allocation) and will be able to look at data 
throughout the study. The Medicago personnel will include 
senior personnel in Scientific and Medical Affairs, Biostatistics, 
Safety, Product Development, and Regulatory Affairs. 
Safety Evaluations: 
Clinical safety assessments will include repeated urine, blood 
chemistry and haematology testing. Safety and tolerability 
endpoints will include immediate adverse events (AEs) 
(30 minutes post-vaccination), solicited local and systemic AEs 
(up to seven days post-vaccination), unsolicited AEs up to 
Day 28, serious AEs (SAEs), AEs leading to withdrawal, AEs of 
special interest (AESIs), medically attended AEs (MAAEs), new 
onset of chronic diseases (NOCDs), and deaths up to the end of 
the study (Day 365). 
Immunogenicity 
Evaluations: 
Vaccine immunogenicity will be evaluated on Day 0, Day 28, 
Day 182, and Day 365, as measured by the serum HI and on 
Day 0 and Day 28 as measured by MN antibody titers.  
Primary Endpoints: 
Safety: 
The primary safety endpoints are: 
x Occurrences, intensity, and relationship to vaccination of 
immediate AEs (30 minutes post-vaccination); 

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x Occurrences and intensity of solicited local and systemic 
AEs (for seven days following study vaccine 
administration); 
x Occurrences, intensity, and relationship of unsolicited AEs 
for 28 days following study vaccine administration; 
x Number and percentage of subjects with normal and 
abnormal, clinically significant urine, haematological and 
blood biochemistry values, and urinalysis at Days 0, 3, 
and 28; 
x Occurrences of SAEs, AEs leading to withdrawal, AESIs, 
MAAEs, NOCDs, and deaths up to Day 28; 
x Occurrences of SAEs, AEs leading to withdrawal, AESIs, 
MAAEs, NOCDs, and deaths from Day 29 up to Day 182; 
x Occurrences of SAEs, AEs leading to withdrawal, AESIs, 
MAAEs, NOCDs, and deaths from Day 183 up to the end 
of the study (Day 365). 
Immunogenicity: 
The primary immunogenicity endpoint is: 
x HI antibody response induced by adjuvanted and 
unadjuvanted QVLP and Fluzone HD Quad against the 
homologous influenza strains on Day 28, compared to 
Day 0 values. HI antibody titers will be analyzed using the 
following parameters: geometric mean titers (GMT), 
seroconversion (SC) rate, seroprotection (SP) rate, and 
geometric mean fold rise (GMFR).  
Secondary Endpoints: 
Immunogenicity: 
The secondary immunogenicity endpoints are: 
x MN antibody response induced by adjuvanted and 
unadjuvanted QVLP and Fluzone HD Quad against the 
homologous influenza strains on Day 28, compared to 
Day 0 values. MN antibody titers will be analyzed using 
the following parameters: GMT, SC rate, and GMFR; 
x HI antibody response induced by adjuvanted and 
unadjuvanted QVLP and Fluzone HD Quad against the 
heterologous influenza strains on Day 28, compared to 
Day 0 values. HI antibody titers will be analyzed using the 
following parameters: GMT, SC rate, SP rate, and GMFR.  
x HI antibody response (against homologous and 
heterologous influenza strains) and MN antibody response 
(against homologous influenza strains) induced by 
adjuvanted and unadjuvanted QVLP and Fluzone HD 

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Quad on Day 28, compared to Day 0 values, stratified by 
prior influenza vaccination status, if >25% of the enrolled 
subjects have received a standard influenza vaccine during 
the 12 months prior to study vaccination;  
x Durability of antibody responses, as determined by HI 
titers against homologous influenza strains (6 and 
12 months post-vaccination); 
Safety: 
The secondary safety endpoints are: 
x Occurrences, intensity, and relationship to vaccination of 
immediate AEs (30 minutes post-vaccination), stratified by 
prior influenza vaccination status, if >25% of the enrolled 
subjects have received a standard influenza vaccine during 
the 12 months prior to study vaccination; 
x Occurrences and intensity of solicited local and systemic 
AEs (for seven days following study vaccine 
administration), stratified by prior influenza vaccination 
status, if >25% of the enrolled subjects have received a 
standard influenza vaccine during the 12 months prior to 
study vaccination; 
x Occurrences, intensity, and relationship of unsolicited AEs 
for 28 days following study vaccine administration, 
stratified by prior influenza vaccination status, if >25% of 
the enrolled subjects have received a standard influenza 
vaccine during the 12 months prior to study vaccination; 
x Number and percentage of subjects with normal and 
abnormal, clinically significant urine, haematological and 
blood biochemistry values, and urinalysis at Days 0, 3, 
and 28, stratified by prior influenza vaccination status, if 
>25% of the enrolled subjects have received a standard 
influenza vaccine during the 12 months prior to study 
vaccination; 
x Occurrences of SAEs, AEs leading to withdrawal, AESIs, 
MAAEs, NOCDs, and deaths up to Day 28, stratified by 
prior influenza vaccination status, if >25% of the enrolled 
subjects have received a standard influenza vaccine during 
the 12 months prior to study vaccination; 
x Occurrences of SAEs, AEs leading to withdrawal, AESIs, 
MAAEs, NOCDs, and deaths from Day 29 up to Day 182, 
stratified by prior influenza vaccination status, if >25% of 
the enrolled subjects have received a standard influenza 
vaccine during the 12 months prior to study vaccination; 

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x Occurrences of SAEs, AEs leading to withdrawal, AESIs, 
MAAEs, NOCDs, and deaths from Day 183 up to the end 
of the study (Day 365), stratified by prior influenza 
vaccination status, if >25% of the enrolled subjects have 
received a standard influenza vaccine during the 12 months 
prior to study vaccination. 
Statistical Methods: 
Populations: 
Statistical analyses will be performed on pre-defined population 
sets (the safety analysis set [SAS], the intention-to-treat [ITT] 
set, and the per protocol [PP] set) according to the Statistical 
Analysis Plan (SAP). 
All safety analyses will be performed using the SAS. The 
analyses of all immunogenicity endpoints will be performed 
using the PP set and the ITT set. The analysis in the PP set will 
be considered the primary analysis for these objectives in order 
to collect information regarding the immunogenicity responses 
that most closely reflect the scientific model underlying the 
protocol. ITT set will be used as sensitivity analysis. 
 
Day 28 and Day 182 Data Analyses: 
The third-party statistical team will perform data analyses after 
Day 28 (last subject) and Day 182 (last subject). The data 
analyses will involve select individuals from the third-party 
statistical team and Medicago who will be unblinded (as 
described in Blinding section above). The Day 28 and Day 182 
data analyses will allow discussions of the clinical data to 
inform study design decisions of the subsequent study, without 
having to wait until after the end of the follow-up period for 
study completion. 
Statistical Analyses: 
All descriptive and inferential statistical analyses will be 
performed using Statistical Analysis System® (SAS®) software 
(version 9.4 or higher). 
In general, categorical data will be summarized using the 
number and percent of subjects in each category and continuous 
data will be summarized using descriptive statistics (mean or 
geometric mean, median, standard deviation, minimum, and 
maximum).  
Analyses of the immunogenicity and safety endpoints will 
include each group as a whole as well as comparisons by prior 
influenza vaccination status, if >25% of the enrolled subjects 

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have received a standard influenza vaccine during the 12 months 
prior to study vaccination. 
Safety Analyses: 
Safety and tolerability endpoints will be summarized by 
treatment using descriptive statistics. 
Immunogenicity Analyses: 
For both HI and MN, point estimates and two-sided 95 % CI for 
all immunogenicity endpoints and responses for the treatment 
groups will be calculated. GMT will be compared among 
treatment groups by using Analysis of Variance (ANOVA) on 
log-transformed data. GMFR will be derived by using Analysis 
of Covariance (ANCOVA) to model the difference in the log of 
the titer values between Day 28/182/365 and Day 0 for the 
HI assay and between Day 28 and Day 0 for the MN assay, with 
treatment group as main effect and baseline titer as covariate. 
For GMT and GMFR comparisons, Tukey’s test will be 
performed to show p-values for the pairwise comparisons 
between treatment groups. Fisher’s exact tests or chi square tests 
will be used to compare SC among treatment groups.  

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ABBREVIATIONS 
ACIP 
Advisory Committee on Immunization Practices 
AE 
adverse event 
ANOVA 
analysis of variance 
BMI 
body mass index 
BP 
blood pressure 
CBER 
Center for Biologics Evaluation and Research 
CI 
confidence interval 
CMI 
cell-mediated immune (response) 
eCRF 
electronic case report form 
FDA 
Food and Drug Administration 
GCP 
good clinical practice 
GMFR 
geometric mean fold rise or seroconversion factor 
GMT 
geometric mean titer 
HI 
hemagglutination inhibition 
HR 
heart rate 
IB 
investigator’s brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
independent ethics committee 
IM 
intramuscular 
IRB 
institutional review board 
ITT 
intention-to-treat 
MAAE 
medically attended adverse event 
MedDRA 
Medical Dictionary for Regulatory Activities 
MN 
microneutralization 
NACI 
National Advisory Committee on Immunization 
NOCD 
new onset of chronic disease 
OT 
oral temperature 
PP 
per protocol 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SAS 
safety analysis set 
SAS® 
Statistical Analysis System® 
SC 
seroconversion 
SP 
seroprotection 
SRH 
single radial hemolysis 
TEAE 
treatment-emergent adverse event 
VLP 
virus-like particle 

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WHO 
World Health Organization 
US 
United States 
 
 
 

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1 
INTRODUCTION 
Seasonal influenza is a potentially serious infection associated with a wide range of clinical 
outcomes across the entire human lifespan. The influenza (A and B) virus genome is an eight-
segment single-stranded RNA with high potential for in situ recombination and mutations for 
host adaptation. Two segments code for the hemagglutinin and neuraminidase antigens that play 
an essential role in virus infectivity. At present, 17 hemagglutinin and ten neuraminidase 
subtypes are known in bird populations and some subtypes routinely circulate in humans, such as 
the A (H1N1), A (H3N2), and B influenza viruses. When a new subtype acquires the capacity for 
human-to-human transmission, this can give rise to a major pandemic like the one caused by an 
H1N1 strain in 1918 referred to as the Spanish flu. Antibodies that bind to the hemagglutinin 
molecule can prevent viral entry into host cells or modify the severity of the infection and are the 
basis on which influenza vaccines are formulated every year. 
Despite continuing advances in understanding of the immune response to natural infection and 
immunization, the disease remains a major cause of morbidity and mortality worldwide. In the 
United States (US) alone, influenza is responsible for approximately 36,000 deaths per year and 
the WHO estimates that influenza causes three to five million cases of severe illness and up to 
650 000 deaths per year [Palache 2011, WHO 2018]. Influenza is also responsible for a massive 
economic burden, with direct medical costs for each winter influenza season estimated at over 
10 billion dollars [Molinari 2007] in the US alone. 
The main strategy for prevention and control of seasonal and pandemic influenza is still 
vaccination. In 2012, the Advisory Committee on Immunization Practices (ACIP) issued the first 
recommendation of national universal seasonal influenza vaccination in the US [Osterholm 
2012]. Currently, various health and disease monitoring agencies around the world continue to 
recommend annual influenza vaccinations and communicate that it is the most effective way to 
prevent influenza [European Centre for Disease Prevention and Control (ECDC) 2018a, 
Grohskopf 2019, NACI 2019].  
Licensure of influenza vaccines is based either on efficacy studies or on surrogate correlates of 
protection. The latter are primarily based on their ability to induce HI titers. Despite the 
existence of these surrogate correlates of protection, recent reviews of vaccine efficacy studies 
suggest that the overall efficacy of currently licensed inactivated trivalent and quadrivalent 
vaccines is highly variable and depends, among other factors, on the “match” between 
circulating strains and the strains used for vaccine production [Lewnard 2018]. Although 
mismatches are not unique to A (H3N2) viruses, the rapid evolution of this family of viruses and 
risk of mutations with egg-based platforms have resulted in serious problems in several recent 
influenza seasons. 
Indeed, the 2014-2015 Northern Hemisphere influenza season was a critical reminder of how the 
efficacy of commercially available vaccines can be affected by strain mismatch.  In that year, 
vaccine effectiveness in North America for A (H3N2) viruses ranged from 19 % [Flannery 2015] 
to 0 % [Skowronski 2015].  The A (H3N2) viruses were once again problematic in the 
2017-2018 influenza season, generally considered to be one of the worst in decades. In Canada, 

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the season was characterized by co-circulation of influenza A (H3N2) and B (Yamagata) viruses 
[Public Health Agency of Canada (PHAC) 2018].  Europe experienced an unusually long 
influenza season characterized by high levels of influenza infection with a significant proportion 
of B / Yamagata strains [ECDC 2018b]. The US experienced a flu season that was mostly 
dominated by A (H3N2) strains [CDC 2018]. In both North America and Europe, the 2017-2018 
flu season was also characterized by reported low effectiveness of influenza vaccines at 
preventing medically-attended influenza-like illness (ILI) ranging from 18 to 54 % overall and 
from 7 to 33 % for A (H3N2) strains [ACIP 2018, Rondy 2018, Shoubaki 2018, 
Skowronski 2018]. This low effectiveness was attributed to antigenic mismatch of the A (H3N2) 
vaccine-strain virus produced in embryonic eggs and circulating strains as well as continued 
evolution (i.e., drift) of wild-type A (H3N2) viruses [Paessler 2017]. 
1.1 
Quadrivalent VLP Influenza Vaccine 
Medicago USA Inc. has developed a plant-based system (Nicotiana benthamiana) for transient 
expression of two type A and two type B influenza strains to produce QVLP intended for active 
immunization for the prevention of influenza disease caused by influenza A subtype viruses and 
type B viruses contained in the vaccine. This vaccine may be able to address several limitations 
of the currently licensed vaccines: 
x The hemagglutinin proteins in each of the four monovalent VLPs are based on the genetic 
sequences of circulating human influenza viruses selected by the WHO; in contrast, 
influenza strains grown in embryonic eggs or tissue culture tend to mutate for optimal 
growth in these substrates; 
x Plant-based VLP manufacturing does not require the use of live viruses. Thus, inactivation 
by chemicals and then splitting by a detergent before injection into humans are not needed, 
as is the process for living non-attenuated viruses. These processes are known to influence 
antigenicity, and antigens displayed on the VLPs are not impacted by the potentially 
denaturing treatments; 
x The plant-based technology used for QVLP produces hemagglutinin proteins from the 
selected influenza strains without introducing undesirable mutations that can occur when 
influenza viruses are grown in egg- and cell-based production platforms [Parker 2016, Wu 
2017, Zost 2017]. Very few microbial pathogens can infect both plants and humans so the 
risk of exposure to potentially pathogenic adventitious agents is greatly reduced; 
x Medicago’s previous clinical data suggests that plant-made VLP vaccines induce not only 
antibodies, but also strong CD4+ T cell immunity which may be important for both the 
persistence of immunity and the provision of better protection in older subjects, who often 
derive significant benefit from vaccination despite little evidence of a humoral response 
[Haq 2014]. 
Nicotiana benthamiana is a non-transgenic plant that is a distant wild relative from Australia of 
the tobacco plant, Nicotiana tabacum. The transfer vector used to move targeted DNA constructs 
into the plant cells is the bacterium Agrobacterium tumefaciens. This vector then directs the 

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expression of the hemagglutinin protein. The hemagglutinin proteins are assembled into trimers 
in the intracellular secretory pathway, aligned at the plant plasma membrane via a 
transmembrane domain, and finally bud out of the plant plasma membrane in the form of VLPs. 
Thus, the viral hemagglutinin proteins are anchored in a lipid bilayer of plant cell origin.  
1.2 
Pre-clinical Studies 
Medicago has conducted several preclinical studies in rats with monovalent, trivalent, and 
quadrivalent formulations. All strains included in the quadrivalent vaccine are immunogenic at 
doses ranging from 0.001 to 10 ȝg in the rat model. Moreover, a repeated-dose toxicity study in 
rats assessing the safety and immunogenicity of QVLP with or without the adjuvant AS03 was 
performed to support this Phase 1/2 clinical study. 
For more comprehensive preclinical information regarding the safety and toxicity of QVLP, refer 
to the current Investigator’s Brochure (IB). 
1.3 
Clinical Studies 
Under the clinical development program for QVLP, Medicago has conducted nine clinical trials 
(eight completed; one ongoing) that included testing with unadjuvanted QVLP over a wide range 
of doses (CP-Q12VLP-004, CP-Q13VLP-007, CP-Q13VLP-008, CP-Q14VLP-009, CP-
Q14VLP-010, CP-PRO-QVLP-011, CP-PRO-QVLP-012, CP-PRO-QVLP-013, and CP-PRO-
QVLP-014). Among these trials, one trial included testing QVLP with an adjuvant (CP-
Q13VLP-008). Study designs and statuses are summarized in Table 2. 
Table 2 Summary of Design of Clinical Studies Performed to Date with QVLP 
Study / Status 
Phase Design 
Population 
N 
Treatment groups 
CP-Q12VLP-004 / 
Completed 
1-2 
Single-center, observer-
blind, randomized, dose-
ranging, placebo-controlled 
study 
Healthy adults 18 to 
49 years of age, 
both genders 
90 (active; ratio 
1:1:1); 
30 (placebo) 
3 ȝg VLP; 
9 ȝg VLP; 
15 ȝg VLP; 
placebo 
CP-Q13VLP-007 / 
Completed 
2A 
Multicenter, observer-blind, 
randomized, dose-ranging, 
placebo-controlled study 
Healthy adults 18 to 
49 years of age, 
both genders 
225 (active; ratio 
1:1:1); 
75 (placebo) 
15 μg VLP; 
30 μg VLP; 
60 μg VLP; 
placebo 
CP-Q13VLP-008 / 
Completed 
2 
Multicenter, observer-blind, 
randomized, dose-ranging, 
placebo-controlled study  
Healthy subjects of 
50 years of age or 
older, both genders 
375 (active; ratio 
1:1:1:1:1); 
75 (placebo) 
15 μg VLP; 
30 μg VLP; 
60 μg VLP; 
7.5 μg VLP + Alhydrogel®; 
15 μg VLP + Alhydrogel®; 
placebo 
CP-Q14VLP-009 / 
Completed 
2 
Multicenter, observer-blind, 
randomized, dose ranging, 
active-comparator clinical 
study 
Healthy adults aged 
18 to 64 years, both 
genders 
604 (active; ratio 
1:1); 
296 (active 
comparator) 
15 μg VLP; 
30 μg VLP; 
15 μg/strain dose of 
FluLaval® Tetra 

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Study / Status 
Phase Design 
Population 
N 
Treatment groups 
CP-Q14VLP-010 / 
Completed 
2 
Multicenter, observer-blind, 
randomized, dose ranging, 
active-comparator clinical 
study 
Healthy subjects of 
65 years of age or 
older, both genders 
499 (active; ratio 
1:1); 
250 (active 
comparator 1); 
252 (active 
comparator 2) 
30 μg VLP; 
60 μg VLP; 
15 μg/strain dose of 
FluLaval® Tetra; 
60 μg/strain dose of Fluzone® 
High Dose 
CP-PRO-QVLP-
013 / Clinic 
completed; Data 
analysis ongoing 
2 
Single-site, observer-blind, 
randomized, active 
comparator-controlled study 
Healthy adults 18 to 
49 years of age and 
65 years of age or 
older, both genders 
Age: 18-49 years: 
25 (VLP); 
Age:  65 years: 
25 (VLP); 
25 (active 
comparator 1); 
25 (active 
comparator 2) 
30 μg VLP;  
15 μg/strain dose of Fluzone® 
Tetra;  
60 μg/strain dose of Fluzone® 
High Dose 
CP-PRO-QVLP-
011 / Completed 
3 
Multicenter, observer-blind, 
randomized, lot consistency 
study 
Healthy adults of 18 
to 49 years of age, 
both genders 
1200 (VLP; 1:1:1 
ratio to one of 
three lots) 
30 μg VLP (three lots) 
CP-PRO-QVLP-
012 / Completed 
3 
Multicenter, observer-blind, 
randomized, placebo-
controlled efficacy study 
Healthy adults of 18 
to 64 years of age, 
both genders 
5064 (VLP); 
5072 (placebo) 
30 μg VLP; 
Placebo 
CP-PRO-QVLP-
014 / Completed 
3 
Multicenter, observer-blind, 
randomized, placebo-
controlled efficacy study 
Healthy adults of  
65 years of age, 
both genders 
6352 (VLP); 
6366 (commercial 
IIV comparator) 
30 μg VLP; 
15 μg QIV (Fluarix® 
Quadrivalent) 
Among the eight completed studies, 14 258 subjects have been exposed to unadjuvanted QVLP 
and 151 subjects have been exposed to adjuvanted QVLP (adjuvanted with Alhydrogel®). Of 
those exposed to unadjuvanted QVLP, 7295 subjects were 18-64 years of age, while 6963 
subjects were 65 years of age and above and of those exposed to adjuvanted QVLP, 75 subjects 
were 50-64 years of age, while 76 subjects were 65 years of age and above. In total, 12 616 of 
these subjects received the 30 μg/strain dose selected for Phase 3 evaluation of the vaccine; 6264 
subjects were 18-64 years of age and 6352 subjects were 65 years of age and above. 
An overview of the available safety and immunogenicity findings from these studies are 
summarized in Section Error! Reference source not found. and Section 1.3.2, respectively. For 
detailed information on these findings, please refer to the current version of the IB. 
1.3.1 Safety Overview for QVLP 
This section summarizes the safety data obtained from the eight completed clinical trials 
performed with unadjuvanted QVLP (CP-Q12VLP-004, CP-Q13VLP-007, CP-Q13VLP-008, 
CP-Q14VLP-009, CP-Q14VLP-010, CP-PRO-QVLP-011, CP-PRO-QVLP-012, and CP-PRO-
QVLP-014) and adjuvanted QVLP (CP-Q13VLP-008); see Table 2 for a description of the basic 
design of these studies, status, and exposure. The incidence of local and systemic reactions 
observed within seven days post-vaccination in these eight studies was consistent with the 
known safety profile for commercial influenza vaccines. The most frequently reported ( 1.0 % 
of subjects) unsolicited TEAEs within 21 days of vaccine administration included arthralgia, 
back pain, diarrhea, fatigue, headache, musculoskeletal pain, myalgia, nasal congestion, 
nasopharyngitis, nausea, oropharyngeal pain, pain in extremity, rhinorrhea, and upper respiratory 

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infection. No notable differences in the incidence of these events were observed between the 
QVLP groups and the active comparators or placebo groups. No safety issues and no notable 
trends were observed with respect to vital signs, clinical laboratory, or physical examinations in 
any of the eight completed studies. 
In these eight completed clinical trials, the incidence of subjects with at least one SAE during the 
overall study period was < 5.0 % in the QVLP groups. No apparent trends with respect to the 
number or types of SAEs were noted. However, there were more SAEs reported among the 
elderly subjects 65 years of age and older compared to the adult subjects 18 to 64 years old. Only 
three SAEs were considered by the site Investigator to be related to the study treatment (all in the 
elderly subjects 65 years of age and older group) and only one of these was for the QVLP group: 
a possible anaphylactic reaction in one subject in the 30 μg/strain QVLP group. There were 
fifteen subjects in the QVLP group who had treatment-emergent adverse events (TEAEs) leading 
to withdrawal from the study and all these subjects received the 30 μg/strain dose and were 
65 years and older.  Only one NOCD for adult subjects 18 to 64 years old who received QVLP 
and only six NOCDs for elderly subjects 65 years and older who received QVLP were reported 
that were considered by the site investigators to be vaccine-related. 
Among the 14 409 subjects who were vaccinated with QVLP (with or without adjuvant), 
13 deaths (neoplasm malignant, myocardial infarction (acute and non-acute), urosepsis, 
pneumonia complications, complications from Alzheimer’s disease, septic endocarditis, 
cerebrovascular accident, acute heart failure, gastrointestinal haemorrhage, and completed 
suicide) were reported after vaccination of 30 μg/strain QVLP. The site Investigators assessed all 
of these events as definitely not related to the study vaccine, with the exception of two events 
(septic endocarditis and completed suicide) that were assessed as probably not related to the 
study vaccine. 
As a precaution, subjects were monitored for TEAEs with a hypersensitivity component 
(reported events were searched using both narrow and broad standardized Medical Dictionary for 
Regulatory Activities (MedDRA®) queries for a possible hypersensitivity component). Based on 
the data from the eight completed studies, there is no definitive evidence of anaphylactic 
reactions associated with use of QVLP in humans. However, a single case of possible, truncated 
anaphylactic reaction in one subject has been reported. A small number of subjects had potential 
hypersensitivity reactions judged to be related to vaccine administration (no more than 0.5 % of 
subjects administered a QVLP treatment experienced one of these events) and the events were 
distributed fairly evenly among treatment groups, including the placebo and the active 
comparator groups. However, since severe reactions are considered to be an important potential 
risk (based on the theoretical risk that using plants for the production of biotherapeutics may 
induce hypersensitivity) the Sponsor will continue to require that appropriate medical treatment 
and supervision are available to manage any possible anaphylactic reactions. 
Safety results from eight completed clinical trials performed show that QVLP was well-tolerated, 
with a safety profile similar to that of the active comparators and to the placebo for systemic 
reactions and TEAEs. 

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1.3.1.1 Safety Overview for AS03 
The adjuvant AS03 is an established effective adjuvant used in the formulations for Arepanrix™ 
and Pandemrix™ and is manufactured by GlaxoSmithKline. Data from clinical trials with over 
55 000 vaccinated subjects showed that AS03-adjuvanted influenza vaccines exhibited an 
acceptable safety profile [Cohet 2019, Garcon 2012, Vaughn 2014]. Increased reactogenicity, 
both local and general, is consistently noted for AS03-adjuvanted vaccines compared with the 
corresponding unadjuvanted vaccines [Garcon 2012, Launay 2013, Nolan 2014, Waddington 
2010]. Most symptoms were mild to moderate in intensity and of short duration. An increased 
risk of narcolepsy was observed in some individuals after the vaccination campaign with 
Pandemrix™ in 2009-2010. A similar risk of narcolepsy was not identified with other non-
adjuvanted influenza vaccines or other AS03-adjuvanted vaccines, like Arepanrix™ 
[Montplaisir 2014, Cohet 2015]. Current data suggest that cases of narcolepsy seen immediately 
following the 2009-2010 pandemic were most likely the result of an immune cascade, triggered 
by CD4 T cell cross-reactivity to HA proteins from the H1N1 virus itself and hypocretin.
Research is continuing to assess whether either of the main components of the 2009/2010 flu 
pandemic vaccine (e.g., the viral proteins in the form used in the vaccine or the AS03 
adjuvant) may have contributed to the reaction. 
1.3.2 Immunogenicity and Efficacy Overview for QVLP 
This section summarizes the immunogenicity data obtained from eight studies conducted with 
adult (18 to 64 years of age) and/or elderly (65 years of age and older) populations. Studies 
CP-Q12VLP-004, CP-Q13VLP-007,  CP-Q14VLP-009, CP-Q14VLP-011, and CP-Q14VLP-012 
were conducted in an adult-only population (18 to 49 years for CP-Q12VLP-004, CP-Q13VLP-
007, and CP-Q14VLP-011, and 18 to 64 years for CP-Q14VLP-009 and CP-Q14VLP-012), 
CP-Q13VLP-008 was conducted in a combined adult and elderly population (50 years and 
older), and CP-Q14VLP-010 and CP-PRO-QVLP-014 were conducted in an elderly-only 
population (65 years of age and older). In addition, efficacy data was obtained from two studies 
conducted with adult (18 to 64 years of age) and elderly (65 years of age and older) populations: 
studies CP-PRO-QVLP-012 and CP-PRO-QVLP-014, respectively. All of these clinical studies 
were performed with unadjuvanted QVLP with the exception of study CP-Q13VLP-008 which 
was performed with both unadjuvanted and adjuvanted QVLP. See Table 2 for a description of 
the basic design of these studies and exposure. 
Overall, the immunogenicity data from the studies conducted show that QVLP induced a 
substantial antibody response in healthy adult (18 to 64 years) and elderly (65 years of age and 
older) populations. The 30 ȝg/strain dose level appeared to be the lowest dose to elicit a 
consistent antibody response and be the most comparable with the commercial licensed vaccines. 
As a result, the 30 ȝg/strain dose level was selected for evaluation during Phase 3 efficacy 
studies in adult and elderly populations. The antibody response to QVLP, as determined by HI, 
MN, and single radial hemolysis (SRH) assays, was generally equivalent or lower compared to 
licensed influenza vaccines. As occurs with all licensed vaccines, the antibody responses induced 
by QVLP in the elderly population tended to be lower than those observed in the younger healthy 

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adult population. QVLP also elicited some cross-protective antibodies against heterologous 
influenza strains (current IB version). 
In all the studies conducted, clear and consistent vaccine-related Day 21 poly-functional CD4+ 
T cell responses were observed with QVLP against all four homologous strains present in the 
vaccines in both the adult and elderly populations. Overall, the 30 ȝg/strain dose level showed 
the highest T cell response induced by QVLP that was at least equivalent (B virus antigens) or 
generally superior (A virus antigens) compared to licensed influenza vaccines. Further, the cell-
mediated immune (CMI) response induced by QVLP appeared to be both durable (up to 
Day 201) and cross-reactive. 
QVLP demonstrated statistically significant protection against respiratory illness and influenza-
like illness, caused by influenza A and B strains, in adults aged 18 to 64 years (CP-PRO-QVLP-
012) that was well-maintained for at least five to six months after vaccination. In the elderly 
population (65 years of age or older), QVLP showed non-inferiority compared to a licensed 
influenza vaccine in the prevention of ILI caused by any influenza strain (CP-PRO-QVLP-014). 
Moreover, it is important to note that there was no decline in protection with QVLP among the 
older age cohorts in either of these two studies and QVLP displayed the greatest protection in the 
oldest subjects ( 75 years of age) in study CP-PRO-QVLP-014. 
1.3.2.1 Immunogenicity and Efficacy Overview for AS03 
The AS03-adjuvanted pandemic influenza vaccines have been shown to be more immunogenic 
than non-adjuvanted vaccines. High efficacy and effectiveness have been demonstrated for 
AS03-adjuvanted H1N1 pandemic influenza vaccines in a wide range of populations [Garcon 
2012]. Clinical data with AS03-adjuvanted antigen-sparing formulations have shown that 
immunization against influenza caused by the potential pandemic subtypes H5N1, H1N1, H7N1, 
H7N9, and H9N2 has demonstrated satisfactory immunogenic potency, as measured by 
haemagglutinin-inhibition titers, with reduced antigen doses in adults [Baz 2013, Jackson 2015, 
Lansbury 2017, Leroux-Roels 2007, Madan 2017, Madan 2017a, Madan 2017b, McElhaney 
2013, Yang 2013, Yin 2011]. Also, AS03-adjuvanted H5N1 vaccines were shown to induce 
cross-clade neutralizing antibody responses [Leroux-Roels 2007] and antibody affinity 
maturation [Khurana 2018]. 
1.4 
Overall Rationale for the Study 
Given the relatively modest antibody responses elicited by QVLP against some strains and 
because the HI antibody response is well recognized by Regulatory Agencies to be a correlate of 
efficacy, Medicago will study the possible advantage of administering QVLP with an adjuvant 
used in licensed vaccine products (AS03).  

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This Phase 1/2 study is to assess the safety, tolerability, and immunogenicity of adjuvanted 
recombinant QVLP in healthy adults 65 years of age and older. One dose of the following 
vaccine formulations will be administered in this study: 
x 30 μg/strain of QVLP adjuvanted with AS03, or  
x 30 μg/strain of QVLP unadjuvanted, or  
x Fluzone HD Quad.  
2 
OBJECTIVES 
2.1 
Primary Objectives 
The primary objectives of this study are: 
Safety: 
x To assess the safety and tolerability of a single dose of QVLP (30 μg/strain) with AS03 
adjuvant compared to QVLP (30 μg/strain) (unadjuvanted) and Fluzone HD Quad; 
Immunogenicity: 
x To assess the immunogenicity of a single dose of QVLP (30 μg/strain) with AS03 adjuvant 
compared to QVLP (30 μg/strain) (unadjuvanted) and Fluzone HD Quad, as measured by 
HI assay against homologous influenza strains. 
2.2 
Secondary Objectives 
The secondary objectives of this study are: 
Immunogenicity: 
x To assess the immunogenicity of a single dose of QVLP (30 μg/strain) with AS03 adjuvant 
compared to QVLP (30 μg/strain) (unadjuvanted) and Fluzone HD Quad, as measured by 
MN assay against homologous influenza strains; 
x To assess the immunogenicity of a single dose of QVLP (30 μg/strain) with AS03 adjuvant 
compared to QVLP (30 μg/strain) (unadjuvanted) and Fluzone HD Quad, as measured by 
HI assay against heterologous influenza strains; 
x To assess the immunogenicity of a single dose of QVLP (30 μg/strain) with AS03 adjuvant 
compared to QVLP (30 μg/strain) (unadjuvanted) and Fluzone HD Quad, as measured by 
HI (homologous and heterologous influenza strains) and MN (homologous influenza 
strains) assays, stratified by prior influenza vaccination status, if >25% of the enrolled 
subjects have received a standard influenza vaccine during the 12 months prior to study 
vaccination; 
x To evaluate the persistence of antibody responses, as determined by HI titers against 
homologous influenza strains, at 6 and 12 months post-vaccination; 
Safety: 
x To assess the safety and tolerability of a single dose of QVLP (30 μg/strain) with AS03 
adjuvant compared to QVLP (30 μg/strain) (unadjuvanted) and Fluzone HD Quad, 

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stratified by prior influenza vaccination status, if >25% of the enrolled subjects have 
received a standard influenza vaccine during the 12 months prior to study vaccination. 
3 
STUDY ADMINISTRATIVE STRUCTURE 
Table 3 Study Administrative Structure 
Role 
Name and Address 
Sponsor 
Medicago USA Inc. 
7 Triangle Drive 
Durham (NC), United States 27713 
 
 
 
 
 
 
 
 
 
 
4 
STUDY DESIGN AND RATIONALE 
4.1 
Overview of Study Design 
This randomized, partially-blinded, active comparator-controlled multi-center, dose-finding, 
Phase 1/2 study will be conducted at multiple sites. The composition of QVLP to be used in this 
study includes a mix of recombinant H1, H3, and two B hemagglutinin proteins expressed as 
VLPs and will be based on the 2020-2021 recommended WHO strains for vaccination in the 
Northern Hemisphere. The compositions of the active comparators are also based on the 
2020-2021 recommended WHO strains for vaccination in the Northern Hemisphere. 
Overall, approximately 120 healthy male and female subjects 65 years of age and older will be 
enrolled evenly into one of three parallel treatment groups, as presented in Table 4. A dose level 
of 30 μg/strain QVLP will be tested with the adjuvant AS03. The 30 μg/strain is the full dose of 
QVLP, used in previous clinical studies.  
Table 4 Study Treatment Groups 
Treatment Group  
Treatments 
Dose Level 
No. of Subjects 
1 
QVLP adjuvanted with AS03 
30 μg/strain 
40 
2 
QVLP unadjuvanted 
30 μg/strain 
40 
3 
Fluzone HD Quad 
60 μg/strain 
40 
The first 3 subjects per treatment group enrolled in the study will receive an IM injection of one 
of the three treatments listed in Table 4. The vaccinations for the first three subjects in each 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

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treatment group will be staggered so that each vaccination must be performed at least 30 minutes 
apart. The seven-day safety data will be collected from these subjects and reviewed by the 
IDMC, prior to permitting the vaccination of the remaining subjects in these three treatment 
groups.  
Subjects will be screened up to seven days in advance of the vaccine administration and will 
demonstrate a satisfactory baseline medical assessment by medical history, general physical 
examination, urinalysis, haematological and blood biochemistry analyses, and serum screening 
for HIV, Hepatitis B and Hepatitis C markers. On Day 0, vaccine administration will occur. 
Phone contacts will be made one day and eight days after the vaccine administration, specifically 
for review of the subject’s safety and concomitant medication data. Visits to the Investigator site 
will occur 3 days after the vaccine administration (Day 3) for key safety assessments and 28 days 
after the vaccine administration (Day 28) for key safety and immunogenicity assessments. 
Subjects will have monthly telephone calls after Day 28 up to the end of the study. Subjects will 
return to the Investigator site on Day 182 for immunogenicity and safety assessments (6-month 
follow-up) and on Day 365 for final immunogenicity and safety assessments (12-month 
follow-up). 
Subjects enrolled and vaccinated in the QVLP (15 μg/strain and 45 μg/strain) adjuvanted with 
AS03 adjuvant (full dose or half dose) and the QVLP (30 μg/strain) adjuvanted with AS03 
adjuvant (half dose) treatment groups will complete study procedures as outlined above and will 
be followed for safety and immunogenicity assessments up to Day 365. 
4.2 
Rationale of Study Design 
4.2.1 Randomization 
Randomization will be used to minimize bias in the assignment of subjects to treatment groups, 
to increase the likelihood that known and unknown subject attributes (e.g. demographic and 
baseline characteristics) are evenly balanced across treatment groups, and to enhance the validity 
of statistical comparisons across treatment groups. 
6XEMHFWV ZLOO EH UDQGRPL]HG DFFRUGLQJ WR prior influenza vaccination status GHILQHG DV
HQUROOHG VXEMHFWV ZKR have received a standard influenza vaccine during the 12 months prior 
to study vaccination 
4.2.2 Blinding 
A partially-blinded treatment trial design consisting of both observer-blind and open-label 
elements will be utilized in this study. Observer-blinded treatment trial design elements will be 
used to reduce potential bias during data collection and evaluation of the study endpoints. Details 
of who will remain blinded during the study are presented in Section 6.2.  
Open-label trial design elements will be used to allow a small number of Medicago personnel to 
remain unblinded throughout the study (see Section 6.2) to make informed design decisions of 

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the subsequent studies based on the Day 28 and Day 182 data analyses (see Section 12.3) results, 
without having to wait until after the end of the follow-up period for study completion. 
4.2.3 
Dose Selection and Dosage Regimen 
In this study, three dose levels (15 μg/strain, 30 μg/strain, and 45 μg/strain) of QVLP will be 
tested in combination with two dose levels of AS03 adjuvant (full and half dose) in a single-dose 
regimen to select a dose level of QVLP and adjuvant dose level-combination that is safe and 
effective for further development. The 30 μg/strain dose is the full dose of QVLP, used in 
previous clinical studies, and the 15 μg/strain dose has been included to assess a possible dose-
sparing effect in combination with the adjuvant AS03. A higher dose of 45 μg/strain will also be 
assessed since higher doses of 45-60 μg/strain are used by two commercially available vaccines 
[Flublok 2020, Fluzone High-Dose 2019] that target the elderly population. 
The dosage and administration of the active comparator unadjuvanted QVLP is based on data 
from previous studies as dose used to establish non-inferior efficacy to another approved 
influenza vaccine in the elderly population. In addition, it is also the dose most comparable with 
commonly used licensed vaccines [Flublok 2020, Fluzone High-Dose 2019] in the elderly. 
The dosage and administration of the active comparator Fluzone HD Quad is in accordance with 
the approved prescribing information for this vaccine.  
4.2.4 Route of Administration 
The route of administration used for adjuvanted QVLP and comparators is the intramuscular 
route, specifically in the deltoid muscle of the arm, since it is a more viable route of 
administration (compared to an oral route), has better absorption compared to the subcutaneous 
route, and is the same route of administration for the active comparators.  
4.2.5 Active Comparators Selection 
The active comparator unadjuvanted QVLP was selected since the safety, immunogenicity, and 
efficacy profile of this vaccine has been established in persons 65 years of age and older in 
previous studies. The same formulation of unadjuvanted QVLP will be used in combination with 
AS03 adjuvant. 
The active comparator Fluzone HD Quad was selected on the basis that this product is an 
approved quadrivalent influenza vaccine for persons 65 years of age and older in the US. In 
addition, this product has been well-studied and has well-established immunogenicity, efficacy, 
and safety profiles for this population.  
4.2.6 
Study Duration 
The duration of this study will be approximately 17 months.  

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5 
STUDY POPULATION 
5.1 
Inclusion Criteria 
Subjects must meet all of the following inclusion criteria at the Screening visit (Visit 1) and/or 
Vaccination visit (Visit 2) to be eligible for participation in this study; no protocol waivers are 
allowed. All Investigator assessment-based judgements must be carefully and fully documented 
in the source documents: 
1. Subjects must have read, understood, and signed the informed consent form (ICF) prior to 
participating in the study; subjects must also complete study-related procedures and 
communicate with the study staff at visits and by phone during the study; 
2. Male and female subjects must be 65 years of age and older at the Vaccination visit 
(Visit 2); 
3. Subject must have a body mass index (BMI) < 35 kg/m2 at the Vaccination visit (Visit 2); 
4. Subjects are considered by the Investigator to be reliable and likely to cooperate with the 
assessment procedures and be available for the duration of the study; 
5. Subjects must be non-institutionalized (e.g. not living in rehabilitation centres or old-age 
homes; living in an elderly community is acceptable) and have no acute or evolving medical 
problems prior to study participation and no clinically relevant abnormalities that could 
jeopardize subject safety or interfere with study assessments, as assessed by the Principal 
Investigator or sub-Investigator (thereafter referred as Investigator) and determined by 
medical history, physical examination, serology, clinical chemistry and haematology tests, 
urinalysis, and vital signs. Investigator discretion will be permitted with this inclusion 
criterion; 
Note: Subjects with a pre-existing chronic disease will be allowed to participate if the 
disease is stable and, according to the Investigator’s judgment that must be documented in 
the source documents, the condition is unlikely to confound the results of the study or pose 
additional risk to the subject by participating in the study. Stable disease is generally defined 
as no new onset or exacerbation of pre-existing chronic disease three months prior to 
vaccination. Based on the Investigator’s judgment and documented in source documentation, 
a subject with more recent stabilization of a disease could also be eligible. 
5.2 
Exclusion Criteria 
Subjects who meet any of the following criteria at the Screening visit (Visit 1) and/or 
Vaccination visit (Visit 2) will not be eligible for participation in this study; no protocol waivers 
are allowed. All Investigator assessment-based judgements must be thoroughly documented in 
the source documents: 
1. According to the Investigator’s opinion, significant acute or chronic, uncontrolled medical 
or neuropsychiatric illness. Acute disease is defined as presence of any moderate or severe 
acute illness with or without a fever within 48 hours prior to the Vaccination visit (Visit 2). 
‘Uncontrolled’ is defined as: 

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x 
Requiring a new medical or surgical treatment during the three months prior to study 
vaccine administration; 
x 
Requiring any significant change in a chronic medication (i.e. drug, dose, frequency) 
during the three months prior to study vaccine administration due to uncontrolled 
symptoms or drug toxicity unless the innocuous nature of the medication change meets 
the criteria outlined in inclusion criterion no. 5 and is appropriately justified and 
documented by the Investigator. 
Investigator discretion is permitted with this exclusion criterion and must be carefully and 
fully documented in the source documents. 
2. Any confirmed or suspected current immunosuppressive condition or immunodeficiency, 
including cancer, human immunodeficiency virus, hepatitis B or C infection (subjects with a 
history of cured hepatitis B or C infection without any signs of immunodeficiency at present 
time are allowed). Investigator discretion is permitted with this exclusion criterion; 
3. Current autoimmune disease requiring systemic treatment (such as rheumatoid arthritis, 
systemic lupus erythematosus, or multiple sclerosis). Investigator discretion is permitted 
with this exclusion criterion, and subjects may be eligible to participate with appropriate 
written justification in the source document (i.e. subjects with a history of autoimmune 
disease who are disease-free without treatment for three years or more, or on stable thyroid 
replacement therapy, mild psoriasis [i.e. a small number of minor plaques requiring no 
systemic treatment], etc.); 
4. Administration of any non-influenza vaccine within 30 days prior to the Vaccination visit 
(Visit 2); planned administration of any vaccine up to Day 28 of the study. Immunization on 
an emergency basis during the study will be evaluated on case-by-case basis by the 
Investigator. 
Note: Administration of an authorized COVID-19 vaccine prior to or during the study is 
acceptable; 
5. Administration of influenza vaccine within six months prior to the Vaccination visit 
(Visit 2); 
6. Administration of any adjuvanted or investigational influenza vaccine within one year prior 
to randomization or planned administration prior to the completion of the study; 
7. Use of any investigational or non-registered product within 30 days or five half-lives, 
whichever is longer, prior to the Vaccination visit (Visit 2) or planned use during the study 
period. Subjects who are in a prolonged post-administration observation period of another 
investigational or marketed drug clinical study, for which there is no ongoing exposure to 
the investigational or marketed product and all scheduled on-site visits are completed, will 
be allowed to take part in this study, if all other eligibility criteria are met; 
8. Administration of any medication or treatment that may alter the vaccine immune 
responses, such as:  
x 
Systemic glucocorticoids at a dose exceeding 10 mg of prednisone (or equivalent) per 
day for more than seven consecutive days or for 10 or more days in total, within one 
month prior to the Vaccination visit (Visit 2). Inhaled, nasal, intraarticular, ophthalmic, 
dermatological, and other topical glucocorticoids are permitted;  

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x 
Cytotoxic, antineoplastic or immunosuppressant drugs - within 36 months prior to the 
Vaccination visit (Visit 2);  
x 
Any immunoglobulin preparations or blood products, blood transfusion – within 
6 months prior to the Vaccination visit (Visit 2); 
9. Use of any prescription antiviral drugs with the intention of COVID-19 prophylaxis, 
including those that are thought to be effective for prevention of COVID-19 but have not 
been licensed for this indication, within one month prior to the Vaccination visit (Visit 2); 
10. Subjects at high risk of contracting SARS-CoV-2/COVID-19 infection, including, but not 
limited to, individuals with known close contact with:  
x 
anyone residing in, visiting, or working at a health care or long-term care institution 
(i.e. long-term care facilities, acute care hospitals, rehabilitation hospitals, mental 
health hospitals, emergency departments);  
x 
anyone with laboratory-confirmed SARS-CoV-2/COVID-19 infection within 2 weeks 
prior to vaccine administration;  
x 
anyone who traveled outside the country for any duration within 30 days before the 
study vaccination; 
11. History of allergy to any of the constituents of QVLP, any components of Fluzone HD 
Quad, the adjuvant AS03, egg, or tobacco; 
12. History of anaphylactic allergic reactions to plants or plants components (including fruits 
and nuts); 
13. Subjects with a history of Guillain-Barré Syndrome; 
14. Personal or family (first-degree relatives) history of narcolepsy; 
15. Use of prophylactic medications (e.g. antihistamines [H1 receptor antagonists], nonsteroidal 
anti-inflammatory drugs [NSAIDs], systemic and topical glucocorticoids, non-opioid and 
opioid analgesics) within 24 hours prior to the Vaccination visit (Visit 2) to prevent or pre-
empt symptoms due to vaccination; 
16. Have a rash, dermatological condition, tattoos, muscle mass, or any other abnormalities at 
the injection site that may interfere with injection site reaction rating. Investigator discretion 
will be permitted with this exclusion criterion; 
17. Subjects identified as an Investigator or employee of the Investigator or clinical site with 
direct involvement in the proposed study, or identified as an immediate family member 
(i.e. parent, spouse, natural or adopted child) of the Investigator or employee with direct 
involvement in the proposed study, or any employees of Medicago. 
5.3 
Prior and Concomitant Therapy 
New or changed medications reported by the subject post-vaccination and through to the end of 
the study will be recorded in the source documents as a concomitant medication as per the 
conditions outlined in the next paragraph. Since AEs may be secondary to new medications, the 
Investigator will explore the reasons for the change or for the new medication intake and 
document these AEs, if any. 

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Concomitant medications must be reported (reason for use, dates of administration, dosage, and 
route) if the use meets the following conditions: 
x Within 30 days preceding vaccination: any treatments and/or medications specifically 
contraindicated (e.g. influenza vaccines, any immunoglobulins or other blood products, or 
any immune modifying drugs, etc.); 
x From randomization to Day 28, inclusive: any medication (including, but not limited to, 
over-the-counter medicines such as aspirin or antacids), vitamins, and mineral supplements; 
x From Day 29 to the end of the study, inclusive: any concomitant medication(s) 
administered to treat a NOCD (see Section 13.1.4 for definition of NOCD), SAE, or AE 
leading to withdrawal; any concomitant medication used to treat an AE that occurred before 
Day 28 and that is still being used afterwards (i.e. on-going use); 
x Any concomitant medication used to treat conditions reported as medical history; 
x Any investigational medication or vaccine; any vaccine not foreseen in the study protocol. 
5.4 
Prohibited Therapy 
The following medications or therapies are prohibited during the conduct of this study:  
1. Administration of any non-influenza vaccine (excluding authorized COVID-19 vaccines) up 
to blood sampling on Day 28 of the study. Immunization on an emergency basis during the 
study will be evaluated on case-by-case basis by the Investigator;   
2. Administration of any adjuvanted or investigational influenza vaccine (other than the study 
vaccine) up to completion of the study; 
3. Use of any investigational or non-registered product during the study period. Subjects may 
not participate in any other investigational or marketed drug study while participating in this 
study until after the study; 
4. Administration of any medication or treatment that may alter the vaccine immune responses, 
such as: 
x 
Systemic glucocorticoids at a dose exceeding 10 mg of prednisone (or equivalent) per 
day for more than seven consecutive days or for 10 or more days in total; 
x 
Cytotoxic, antineoplastic, or immunosuppressant drugs; 
x 
Any immunoglobulin preparations or blood products, or blood transfusion; 
5. Use of prophylactic medications (e.g. antihistamines [H1 receptor antagonists], nonsteroidal 
anti-inflammatory drugs [NSAIDs], systemic and topical glucocorticoids, non-opioid and 
opioid analgesics) for seven days post-vaccination to prevent or pre-empt symptoms due to 
vaccination; 
6. Use of any prescription antiviral drugs with the intention of COVID-19 prophylaxis, 
including those that are thought to be effective for prevention of COVID-19 but have not 
been licensed for this indication, during the study. 

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If one of the first five criteria is met by a subject during the study (after vaccination), the subject 
may still remain in the study however the inclusion of the subject’s data within the PP set, 
ITT set, or SAS may be impacted.   
Given that an important objective of this study is to evaluate the tolerability of the study vaccine, 
the use of prophylactic medications to prevent or pre-empt symptoms due to vaccination is 
specifically prohibited up to Day 7 (end of collection of solicited symptoms). A prophylactic 
medication is a medication administered in the absence of ANY symptom and in anticipation of 
a reaction to the vaccination (e.g. an antipyretic is considered to be prophylactic when it is given 
in the absence of fever or any other symptoms, to prevent fever from occurring, vitamins used to 
boost immune system, etc.). 
6 
TREATMENT ALLOCATION AND BLINDING 
6.1 
Randomization 
Potential study subjects will be screened and assigned a six-digit subject number. Once all 
screening procedures, including Day 0 pre-randomization procedures, have been completed and 
the study eligibility is confirmed by the Investigator, the randomization numbers will be 
allocated to subjects within the appropriate treatment group by the randomization system. If a 
subject is randomized in error (i.e. does not meet eligibility criteria) and has not been vaccinated, 
then another eligible subject can be randomized to replace this subject. 
Once a randomization number has been assigned, it will not be re-used for any reason. No 
subjects will be randomized into the study more than once. If a randomization number is 
allocated incorrectly, no attempt will be made to remedy the error once the study vaccine has 
been dispensed: the subject will continue on the study with the assigned randomization number 
and associated treatment. The study staff will notify the Sponsor Contact as soon as the error is 
discovered without disclosing the study vaccine administered. Admission of subsequent eligible 
subjects will continue using the next unallocated number in the sequence. 
Randomization will be stratified by prior influenza vaccination status (defined as enrolled 
subjects who have received a standard influenza vaccine during the 12 months prior to study 
vaccination. Subjects will then be enrolled into one of three treatment groups, based on a 
computer-generated randomization schedule prepared by or under the supervision of Medicago 
before the study. The randomization number and treatment will be recorded for each subject in 
the investigational product accountability log.  
6.2 
Blinding 
This is a partially-blinded study: the subjects, the Investigator and all personnel involved in the 
clinical conduct of the study (except the staff involved in the preparation and administration of 
the study vaccine, the quality assurance auditor, and quality control reviewers), Medicago 
clinical and medical staff involved in safety evaluations (e.g. causality assessments), and all 
personnel involved in sample analysis at the central and testing (HI and MN assays) laboratories 

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will not have access to treatment allocation (i.e. randomization codes) for the entire duration of 
the study.   
The IDMC and the independent statistician involved in the preparation of the safety data 
summary for the IDMC reviews will have access to or be aware of treatment allocation (i.e. be 
“unblinded”). The IDMC will review safety data and will make recommendations for the entire 
duration of the study. 
In addition, select personnel of the third-party statistical team will have access to treatment 
allocation (i.e. be “unblinded”) for the entire duration of the study since these personnel will be 
involved in the Day 28 and Day 182 data analyses (see Section 12.3). 
A small number of Medicago personnel will have access to treatment allocation (i.e. be 
unblinded” to results and/or treatment allocation) and will be able to look at data throughout the 
study. The Medicago personnel will include senior personnel in Scientific and Medical Affairs, 
Biostatistics, Safety, Product Development, and Regulatory Affairs. The unblinded procedure 
will be strictly followed, and the process of unblinding and the selected individuals will be 
documented in writing.  
Although there may be some visual differences in QVLP, the adjuvant, and the active 
comparator preparations (e.g. possibly physical appearance), the site staff involved in the 
preparation and administration of the treatments will not be involved in any activity that could 
introduce a bias, such as the evaluations of AEs, or reactogenicity of the subjects following 
vaccination. 
Any code break will be documented and reported to Medicago (or its designee) in a timely 
manner. In a medical emergency, the Investigator may unblind the treatment for that subject 
without prior consultation with the Sponsor. In such an event, the Investigator will need to 
contact the responsible Medical Monitor as soon as possible after the unblinding to discuss the 
case. The treatment allocation should not be disclosed by the Investigator to the responsible 
Medical Monitor. 
The third-party statistical team will perform data analyses after Day 28 (last subject) and 
Day 182 (last subject). The data analyses will involve select individuals from the third-party 
statistical team and Medicago who will be unblinded (as described above). The Day 28 and 
Day 182 data analyses will allow discussions of the clinical data to inform study design decisions 
of the subsequent study, without having to wait until after the end of the follow-up period for 
study completion. 
Since the study is carried out over approximately 17 months and study design for the subsequent 
study needs will be determined in advance (this is also true for the batch(es) manufacturing for 
the subsequent study), a risk assessment will be performed to verify that 1) processes were 
maintained to ensure against operational bias; 2) data breach did not occur that could 
compromise the integrity of the trial and veracity of the data. Said risk assessment will be 
completed prior to initiating any unblinding process; moreover, in relation to the study protocol, 

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the assessment will evaluate relevant procedures, policies, SAP, data transfer and communication 
plans, IT system validation and its adequacy in functionally supporting Medicago’s study. 
7 
DOSAGE AND ADMINISTRATION 
On Day 0, subjects will receive one IM injection into the deltoid region of the non-dominant (if 
possible) arm, of their assigned treatment: 
x 30 μg/strain of QVLP adjuvanted with AS03, or  
x 30 μg/strain of QVLP unadjuvanted, or  
x Fluzone HD Quad. 
The volume of injection will be 0.7 mL for all treatments. 
8 
SPECIMENS AND CLINICAL SUPPLIES 
8.1 
Management of Samples 
Blood samples for biochemistry, haematology, and serology (for HIV, Hepatitis B, and 
Hepatitis C) will be collected at screening and/or during the study as well as urine samples for 
urinalysis. 
Blood samples for immunogenicity analysis will be collected during the study. Should a subject 
be discontinued from the study, a sample will be drawn at the time of the final safety visit and 
sent to Medicago for analysis. Analysis of the immunogenicity blood samples will be conducted 
at central laboratories. 
Complete information on the handling, storage, and shipment of all laboratory samples will be 
described in the study-specific documentation. 
8.2 
Collection of Samples 
Blood samples for biochemistry and haematology will be collected at screening and Days 3 and 
28. Serology tests for HIV, Hepatitis B, and Hepatitis C will be conducted at screening. Sample 
collected during the screening visit should be performed under fasting conditions (approximately 
12 hours) for cholesterol and triglyceride analysis. Note that cholesterol and triglyceride analysis 
will be performed only at screening. Urine samples for testing will be collected at screening and 
Days 3 and 28. 
Blood samples will be collected from each subject immediately prior to study treatment 
administrations on Day 0 and on Days 28, 182, and 365 for serological (immunogenicity) assays. 
8.3 
Clinical Supplies 
The study center will be provided with or be responsible for the provision of supplies for blood 
collection and shipment (e.g. aliquot tubes, aliquot labels, aliquot storage, shipping boxes, and 
accompanying manifests) as described in the study-specific documentation. Sites will be 
authorized to use their own materials if agreed to by Medicago (or its designee). 

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9 
TREATMENT COMPLIANCE 
Study treatments will be prepared and administered by trained unblinded site staff via IM 
injection to each subject at each Investigator site. In addition, the Investigator or designated 
study center personnel will maintain a log of all study treatments dispensed and administered to 
the subject. Investigational product inventory and accountability will be managed throughout the 
study by unblinded site staff (details will be provided in the study-specific documentation). If an 
eligible subject refuses vaccination post-randomization, the reason will be documented in the 
source and electronic case report form (eCRF). 
10 STUDY EVALUATIONS 
10.1 Study Procedures 
10.1.1 Overview 
The Time and Events Schedule: General Information (see Table 1) summarizes the frequency 
and timing of scheduled assessments applicable to this study. 
All subjects will have blood sampled. Subjects will have blood volumes drawn of approximately 
64 mL over a period of 365 days (Table 5). 
Table 5 Estimated Blood Volume Drawn 
Type of Sample 
Volume 
per 
Sample 
(mL) 
 
Number of Samples per Subject 
Total 
Volume of 
Blood per 
Subject 
(mL) 
Visit 
1 
Visit 
2 
Visit 
3 
Visit 
4 
Visit 
5 
Visit 
6 
Total 
Biochemistry, 
haematology, and serology 
(HIV, Hepatitis B & C)* 
8 
1 
 
1 
1 
 
 
3 
24 
Serology for 
immunogenicity 
10 
 
1 
 
1 
1 
1 
4 
40 
Total volume of blood per 
subject (mL) 
 
8 
10 
8 
18 
10 
10 
 
64 
*Serology tests for HIV, Hepatitis B and C will only be performed at Visit 1. 
10.1.2 General COVID-19 Precautions at Clinical Sites 
Sites participating in this study will have processes in place locally for following 
recommendations of the local Public Health authorities for the management of COVID-19. 
Subjects will be asked to follow good hygiene and safe physical distancing measures such as 
wearing a face mask on site, frequent hand hygiene, and maintaining a physical distance of 
2 meters (or 6 feet) from others, except during procedures where staff must come into close 
proximity of subjects (e.g. vaccination, blood draws, collecting vital sign measurements).  
Staff at the clinical sites will also follow the same good hygiene and safe physical distancing 
measures as the subjects at the site. In addition, the staff will be responsible for disinfecting 
materials and/or areas between each use by subjects and staff. All staff involved with on-site 

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procedures will have a back-up member who is qualified to perform the same duties / 
responsibilities in the event that a member of the staff is infected with SARS-CoV-2 or comes 
into contact with an individual known to have COVID-19 and is restricted to self-isolation and 
following the recommendations of the local Public Health authorities for the management of 
COVID-19. 
Subjects will be asked to inform the clinical site if they have tested positive for COVID-19 and if 
they are following the recommended actions (e.g. quarantine, re-testing) by local Public Health 
authorities. Subjects will be asked to not visit the clinic site until after they have fully recovered 
(i.e. no more clinical symptoms) and completed all of the recommended actions (e.g. quarantine, 
re-testing) by local Public Health authorities. If the quarantine period for the subject overlaps 
with a post-vaccination clinical site visit and the visit window, then the procedures for that 
particular visit will be performed by trained medical staff, using reliable personal protective 
equipment and following good hygiene, at the subject’s home (or place of quarantine).   
10.1.3 Screening (Visit 1) 
The following procedures will be performed at the initial screening visit (Visit 1): 
x Review and proceed with the signature of the ICF. The Investigator or his/her designee, 
will fully inform the subject of the nature and scope of the study, potential risks and 
benefits of participation, and the study procedures involved and will answer all questions 
prior to requesting the subject’s signature on the ICF. The subject’s consent must be 
obtained prior to performing any study-related procedures; this must be clearly recorded 
and a copy of the signed ICF retained in the source documents. A copy of the ICF must be 
provided to the subject; 
x Review the inclusion and exclusion criteria and determine the subject’s eligibility to 
participate in this study. The eligibility must be confirmed by the Investigator after review 
of all procedures and findings and prior to randomization; 
x Collect and review demographics (gender, date of birth, age, race, and ethnicity) and body 
measurements (BMI, weight [kg or lbs], and height [cm or inches]) data. BMI is to be 
calculated as body weight (kg) divided by the square of height (m); the BMI result will be 
rounded to one decimal place using the standard convention. For the measurement of body 
weight, subjects will be lightly clothed, without shoes; 
x Collect and review medical history, including the grade of any medical conditions (medical 
conditions are to be graded using the same scale as for AEs; see Section 13.1.2). The 
medical history should record significant problems active at the time of screening and 
present within the preceding six months. Problems that have been clinically inactive for 
more than six months preceding screening, but which might alter the subject’s current or 
future medical management, should also be noted (e.g. cancer, autoimmune disease, known 
mitral valve prolapse or a remote history of a seizure disorder); 
x 
Review and record current and previous medication use (up to 30 days prior to study 
vaccine administration), with the following exception (refer to exclusion criterion 8): 

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x 
For subjects who have been administered the following medication or treatment, review 
and record current and previous medication use up to the time period specified for the 
medication or treatment: 
x 
cytotoxic, antineoplastic, or immunosuppressant drugs – within 36 months prior to 
vaccination;  
x 
any immunoglobulin preparations or blood products, blood transfusions – within 
6 months prior to vaccination; 
x Record influenza vaccinations received within 24 months prior to the administration of the 
study vaccine; 
x Perform a vital signs measurement, including resting blood pressure (BP), heart rate (HR), 
and oral temperature (OT). OT will be collected in degrees Celsius or Fahrenheit using a 
digital thermometer. The OT measurement should not be collected immediately following 
consumption of a hot or cold beverage or after smoking. The BP will be taken after the 
subject has been in a seated position as per the site’s standard procedure. The BP should be 
taken by cuff (manual or automated are both acceptable). BP and HR may be repeated once 
if judged necessary. All measurements (including any repeats) will be recorded in the 
source documents. Inclusion of subjects with an out-of-range BP or HR measurement will 
be based on the Investigator’s judgment; 
x Perform a history- or symptom-directed physical examination. The physical exam will be 
performed by the Investigator or sub-Investigator; 
x Collect screening blood samples for biochemistry, haematology, and serology (HIV, 
Hepatitis B, and Hepatitis C) for analysis. Sample blood collection at the screening visit 
should be performed under fasting conditions (approximately 12 hours) for cholesterol and 
triglyceride analyses; 
x Perform urinalysis on all subjects. 
10.1.4 Vaccination (Day 0) (Visit 2) 
Emergency equipment must be available on site and appropriate treatment must be instituted as 
soon as possible in the event of anaphylaxis or any other immediate hypersensitivity reaction. 
The Investigator will be on-site on vaccine administration days and for the duration of the 
observation period (minimum of 30 minutes after vaccination) for the last subject dosed on that 
day. The Investigator will be available on call for the remainder of the study. A physician should 
be immediately available at the clinical site to administer treatment or to apply procedures for 
any immediate AEs/SAEs. 
10.1.4.1 Prior to Vaccination 
The following procedures will be performed on Day 0 (Visit 2) prior to vaccination:  
x Record changes in medical history and medications and confirm that the subject continues 
to meet all inclusion and no exclusion criteria; 

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x Perform a vital signs measurement, including resting BP, HR, and OT. OT will be collected 
in degrees Celsius or Fahrenheit using a digital thermometer. The OT measurement should 
not be collected immediately following consumption of a hot or cold beverage or after 
smoking. The BP will be taken after the subject has been in a seated position as per the 
site’s standard procedure. The BP should be taken by cuff (manual or automated are both 
acceptable). BP and HR may be repeated once if judged necessary. All measurements 
(including any repeats) will be recorded in the source documents. Inclusion of subjects with 
an out-of-range BP or HR measurement will be based on the Investigator’s judgment; 
x Measure the BMI; for this visit, only weight will be measured while the height will be 
obtained from that measured at the initial screening visit. The BMI result will be rounded to 
one decimal place using the standard convention. For the measurement of body weight, 
subjects will be lightly clothed, without shoes; 
x Perform a history- or symptom-directed physical examination. The physical exam will be 
performed by the Investigator or sub-Investigator; 
x If the subject is judged eligible for the study and is still willing to participate in the study, 
randomize the subject into the study; 
x After confirmation of eligibility, collect baseline blood samples for immunogenicity 
(serology) assessments and prepare and store these samples until shipment to the analytical 
laboratory. 
10.1.4.2 Vaccination 
Once all pre-vaccination procedures have been completed and subject eligibility determined, the 
study vaccine will be administered (on Day 0) IM into the deltoid muscle of the non-dominant (if 
possible) arm, as described in the Investigational Product Management Manual. In order to 
prevent possible confounding of vaccination site reactions, whenever possible, blood samples 
will not be collected from the same arm as the one used for vaccination. The arms used, both for 
blood collection and vaccination, will be documented in the source documents. For subjects with 
BMI < 30 kg/m2, a 23 gauge needle of at least one inch or 2.5 cm in length can be used for 
vaccination. For subjects with BMI  30 kg/m2, a needle of at least 1.5 inches or 3.5 cm in length 
must be used to ensure intramuscular delivery. 
10.1.4.3 Thirty Minutes Post-vaccination 
The post-vaccination observations will be performed by a blinded site staff member. The 
following safety observation procedures will be performed for all subjects immediately 
following study vaccine administration: 
x Subjects will remain in the clinic for at least 30 minutes post-vaccination for observation. 
The observation period will include an assessment of immediate solicited local and 
systemic AEs. Solicited local and systemic AEs occurring within 30 minutes post-
vaccination will be recorded in the subject diary (manual or electronic) and corresponding 
eCRF. All unsolicited AEs occurring within 30 minutes post-vaccination will be recorded 

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in the subject source and AE eCRF. Any unusual signs or symptoms reported during the 
initial 30 minutes post-vaccination will result in continued close monitoring. Based on their 
condition, subjects may be asked to remain in the clinic for their safety for more than 
30 minutes after vaccination (the reason will be recorded in the source documents). All data 
(including the assessment of solicited local and systemic AEs) will be recorded in the 
source documents during and after the observation period. Refer to Section 10.2.1 for 
details regarding the assessment of AEs and/or solicited local and systemic AEs; 
x During the observation period, subjects will be provided with a measurement device 
template (Section 19.1) for measuring (in mm) solicited local AEs of erythema (redness) 
and swelling and an oral digital thermometer for recording daily temperature (in degrees 
Celsius or Fahrenheit). Subjects will also be provided with a diary (manual or electronic; 
Section 19.2) and will be shown how to enter their data in the diary. Each subject will be 
provided with the following instructions on the measurements they are to make: 
x 
How to collect his/her OT in degrees Celsius or Fahrenheit with the provided digital 
thermometer: 
x 
From the evening of Day 0 to the evening of Day 7, the subject will measure his/her OT 
at approximately the same time each evening and will record the results; 
x 
The OT should not be collected immediately following consumption of a hot or cold 
beverage or after smoking. 
x 
The subject is to also take his/her OT if he/she feels feverish and to record the highest 
temperature of the day. In the event that a temperature  38.0 °C or  100.4 °F is 
obtained, the subject will be allowed to take over-the-counter antipyretics 
(e.g. acetaminophen/paracetamol, aspirin, naproxen, or ibuprofen) and will be advised 
to increase the frequency of OT measurements to approximately every four hours, until 
he/she is no longer febrile (fever is defined as a temperature of  38.0 ºC or 
 100.4 °F). The subject is to document medication intake, which will be reviewed by 
the site personnel; 
x 
How to measure any solicited local AEs, including erythema (redness) and swelling 
diameter at the injection site using the measurement template supplied for this purpose; 
subjects will also be requested to evaluate pain at the injection site. Local AEs will be 
assessed every day starting in the evening of Day 0 and up to the evening of Day 7 and 
the results will be recorded. The severity of solicited local AEs will be graded according 
to the Food and Drug Administration (FDA) Guidance for Industry: Toxicity Grading 
Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine 
Clinical Trials [FDA 2007], as presented in Table 6. 
x 
How to grade, on a daily basis from the evening of Day 0 through to the evening of 
Day 7, each of the solicited systemic AEs and their severity (as per the same guidance 
used for solicited local AEs; see Table 6) [FDA 2007] and to record the worst grade of 
the day for each of these solicited systemic AE. The instructions will include how to 
examine and grade swelling in the neck and axilla and to record any unusual feeling 
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x 
Subjects will be advised that they will be asked about the occurrence of any symptoms or 
events requiring medical attention and the use of any concomitant medication during the 
28-day post-vaccination period and until the end of the study. Subjects will also be 
provided with a memory aid (manual or electronic; Section 19.3) to record unsolicited 
AEs and any concomitant medication use and will be shown how to enter their data in the 
memory aid; 
x 
Subjects will be instructed to contact the clinical site for any unsolicited AEs and/or 
solicited local and systemic AEs of greater than Grade 2 (moderate). Based on their 
condition, the Investigator may request that the subject return to the clinic for evaluation; 
x 
Subjects will be advised on emergency contact information and instructions for 
contacting study personnel. Subjects will be advised to immediately contact the 
Investigator (or his/her designee) in the event of an SAE or a medical emergency. 
Subjects will be provided with a phone contact number and be instructed to call if any 
suspected reaction to the vaccination is felt to be significant or of concern; 
x 
Subjects will be advised to notify their health care professional(s) (e.g. primary care 
physician) that they are participating in a clinical research study of an influenza vaccine; 
x After the 30-minute observation period (allowed window of + 15 minutes) is completed, 
measure vital signs (BP, HR, and OT) as described in Section 10.2.1.4. Any out-of-range 
measurements will be assessed by the Investigator (or his/her designee) and any further 
action will be determined upon his/her medical decision; 
x Instruct the subjects to perform measurements of local and systemic AEs at approximately 
the same time each day from Day 0 to Day 7 (preferably in the evening); 
x Advise subjects to report to the clinical site if they have tested positive for COVID-19;  
x Provide appointments (date and time) for the next planned visit to the clinical site (Day 3) 
and also for the Days 1 and 8 phone contacts; 
x The subject will be released from the clinical site once all Day 0 post-vaccination 
procedures have been completed and the subject is in stable condition. 
10.1.5 Day 1 and Day 8 (Telephone Contact) 
The post-vaccination phone contacts will be performed by blinded site staff members. The 
following procedures will be performed during the phone contact (acceptable interval of + 1 day 
for Day 1 and + 1 day for Day 8): 
x Ask the subjects about any difficulties in recording their data, any change in health, any 
visits to health care facilities and/or medical practitioners, and any use of concomitant 
medications. Record the information in the source documents; 
x For any unsolicited AEs and/or solicited local and systemic AEs of greater than Grade 2 
(moderate), the Investigator should be informed within 48 hours of the time the clinical site 
is made aware of the event. The Investigator may request that the subject return to the clinic 
for evaluation; 

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x Advise subjects to immediately contact the Investigator (or his/her designee) in the event of 
any AE that requires medical attention. Subjects will be provided with a phone contact 
number and be instructed to call if any suspected reaction to the vaccination is felt to be 
significant or of concern; 
x Instruct the subjects to contact the clinical site immediately in case they were tested 
positive for COVID-19; 
x Remind the subjects how to measure and record any solicited local and systemic AEs. 
Subjects should also be reminded to record any changes in health, including changes in 
AEs and changes in medications; 
x Remind subjects of their next appointment (date and time) for the clinical visit and/or the 
next phone contact. Subjects will also be reminded to record their data in their diary and 
memory aid in a timely manner. 
In the event that a subject cannot be reached via phone, he/she may be contacted by text message 
or via email (if these contacts are available). However, the phone should be the initial and 
preferred means of communication. At least three attempts within allowed time window should 
be made in order to reach the subject. 
10.1.6 Day 3 Follow-up (Visit 3) 
The post-vaccination follow-up visit procedures will be performed by blinded site staff members 
at the clinical site. For subjects in quarantine, these procedures will be performed by blinded 
trained medical staff at the subject’s home (or place of quarantine). The following procedures 
will be performed during the Day 3 visit (± 1 day): 
x Perform a vital signs measurement, including resting BP, HR, and OT; 
x Perform a history- or symptom-directed physical examination. The physical exam will be 
performed by the Investigator or sub-Investigator; 
x Collect blood samples for biochemistry and haematology; 
x Perform urinalysis on all subjects; 
x Review the diary and memory aid content with the subject to ensure appropriate 
completion. Corrections must be made by the subject him/herself and all corrections must 
be initialed and dated; 
x Review the subject’s safety data and ensure all updates on concomitant medication usage 
and any changes in the subject’s health (AEs, SAEs, AESIs, MAAEs, or NOCDs) are 
recorded appropriately; 
x Advise the subjects to immediately contact the Investigator or his/her designee, in the event 
of any AE that requires a visit to an emergency room and/or hospitalization; 
x Instruct the subjects to contact the clinical site immediately in case they were tested 
positive for COVID-19; 
x Remind the subjects of their next phone contact (date and time). 

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10.1.7 Day 28 (Visit 4) 
The post-vaccination follow-up visit procedures will be performed by blinded site staff members 
at the clinical site. For subjects in quarantine, these procedures will be performed by blinded 
trained medical staff at the subject’s home (or place of quarantine). For all subjects a safety 
follow-up will be performed on or shortly after Day 28 (± 2 days): 
x Perform a vital signs measurement, including resting BP, HR, and OT; 
x Perform urinalysis on all subjects; 
x Collect blood samples for biochemistry and haematology; 
x Collect blood samples for immunogenicity (serology) assessments and prepare and store 
these samples until shipment to the analytical laboratories. 
x Review the diary and memory aid content with the subject to ensure appropriate 
completion. Corrections must be made by the subject him/herself and all corrections must 
be initialed and dated. Collect manual diary and memory aid and provide subjects with just 
a memory aid for the collection of safety data from Day 29 to Day 182; 
x Review the subject’s safety data and ensure all updates on concomitant medication usage 
and any changes in the subject’s health (AEs, SAEs, AESIs, MAAEs, or NOCDs) are 
recorded appropriately; 
x Advise the subjects to immediately contact the Investigator or his/her designee, in the event 
of any AE that requires a visit to an emergency room and/or hospitalization; 
x Provide appointments (date and time) for the next telephone contacts and the next planned 
visit to the clinical site (Day 182). 
10.1.8 Monthly Calls Thereafter (Telephone Contact) 
Subjects should be contacted by telephone once every month (every 30 days ± 14 days; Day 28 
visit date as starting reference). The post-vaccination monthly phone contacts will be performed 
by blinded site staff members. The following procedures will be performed during the phone 
contacts:  
x Ask the subjects about any change in health (AEs ongoing from Day 28, SAEs, AESIs, 
MAAEs, or NOCDs), any visits to health care facilities, and/or medical practitioners and 
use of any concomitant medications. Record the information in the source documents;  
x Advise the subjects to immediately contact the Investigator (or his/her designee), in the 
event of any AE which require a visit to the emergency and/or hospitalization; 
x Instruct the subjects to contact the clinical site immediately in case they were tested 
positive for COVID-19; 
x Remind the subjects of their next appointment (date and time) for the next telephone 
contact and/or the next planned visit to the clinical site (Day 182 or Day 365); 
x Inform the subjects that during the subsequent visit to the clinical site, they will be 
questioned regarding any events that may have occurred since the last contact. 

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In the event that a subject cannot be reached via telephone, he/she may be contacted by text 
message or via email (if these contacts are available). However, the telephone should be the 
initial and preferred means of communication. At least three attempts within allowed time 
window should be made in order to reach the subject. 
10.1.9 Day 182 (Visit 5) 
For some subjects, the Day 182 visit may occur during the time the subject may want to receive 
the 2021-2022 seasonal influenza vaccine. Hence, the tests/procedures (including 
immunogenicity sample collection) originally planned for the Day 182 visit will be collected at 
the Day 182 timepoint or immediately prior to administration of the 2021-2022 seasonal 
influenza vaccine (whichever comes first). 
The post-vaccination visit procedures will be performed by blinded site staff members at the 
clinical site. For subjects in quarantine, these procedures will be performed by blinded trained 
medical staff at the subject’s home (or place of quarantine). The following procedures will be 
performed during the Day 182 visit (± 14 days): 
x Review the memory aid content with the subject to ensure appropriate completion. 
Corrections must be made by the subject him/herself and all corrections must be initialed 
and dated. Collect manual memory aid and provide subjects with another memory aid for 
the collection of safety data from Day 183 to Day 365; 
x Review the subject’s safety data and ensure all updates on concomitant medication usage 
and any changes in the subject’s health (AEs ongoing from Day 28, SAEs, AESIs, MAAEs, 
or NOCDs) are recorded appropriately; 
x Confirm that the subject has continued to comply with protocol requirements (e.g. no use of 
prohibited concomitant medications); 
x Perform a vital signs measurement, including resting BP, HR, and OT; 
x Collect blood samples for immunogenicity (serology) assessments and prepare and store 
these samples until shipment to the analytical laboratories. 
10.1.10 Final Visit – Day 365 (Visit 6) 
The post-vaccination final visit procedures will be performed by blinded site staff members at 
the clinical site. For subjects in quarantine, these procedures will be performed by blinded 
trained medical staff at the subject’s home (or place of quarantine). The following procedures 
will be performed during the Day 365 visit (± 14 days): 
x Review the subject’s safety data and ensure all updates on concomitant medication usage 
and any changes in the subject’s health (AEs ongoing from Day 28, SAEs, AESIs, MAAEs, 
or NOCDs) are recorded appropriately. Collect the subject’s memory aid; 
x Confirm that the subject has continued to comply with protocol requirements (e.g. no use of 
prohibited concomitant medications); 
x Perform a vital signs measurement, including resting BP, HR, and OT; 

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x Collect blood samples for immunogenicity (serology) assessments and prepare and store 
these samples until shipment to the analytical laboratories. 
Any subject who withdraws consent from the study will be asked to undergo Day 365 visit 
(Visit 6) procedures within two weeks of withdrawal, if the subject agrees. 
10.2 Safety 
10.2.1 Evaluations 
Safety and tolerability will be evaluated by solicited local and systemic AEs (immediate AEs 
within 30 minutes post-vaccination and solicited AEs up to seven days post-vaccination), 
unsolicited AEs up to 28 days post-vaccination (including immediate unsolicited AEs within 
30 minutes post-vaccination), and SAEs, AESIs, MAAEs, NOCDs, and AEs leading to 
withdrawal up to the end of the study. In addition, events will be monitored for a possible 
hypersensitivity component and potential immune-mediated diseases from all reported events 
during the study (collected AEs, SAEs, AESIs, NOCDs, and AEs leading to withdrawal). 
Clinical safety methods will include repeated urine, blood chemistry and haematology testing. 
10.2.1.1 Solicited Local and Systemic AEs 
Subjects will be monitored for both solicited local AEs (erythema, swelling, and pain at the 
injection site) and solicited systemic AEs (fever, headache, fatigue, muscle aches, joint aches, 
chills, a feeling of general discomfort, swelling in the axilla, and swelling in the neck) from the 
time of vaccination through Day 7. While the subjects remain in the clinic following vaccine 
administration (at least 30 minutes), staff will monitor them for local and systemic AEs; after 
release from the clinic facility, from the evening of Day 0 to the evening of Day 7, subjects will 
measure and record their local and systemic AEs in their diary. 
The intensity of the solicited local and systemic AEs will be assessed by the subject, documented 
in the diary, and graded as: mild (1), moderate (2), severe (3) or potentially life threatening (4) 
(please refer to Table 6). The causal relationship of all solicited local and systemic AEs will be 
considered related. 
The Investigator should assess solicited AEs and determine if any meet the criteria for SAE.  
Any solicited local or systemic AEs that meet the criteria for SAE should be reported to the 
Sponsor within 24 hours (Section 13.1.6) and entered as an SAE in the eCRF.  

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Table 6 Severity Grades for Solicited Local and Systemic AEs 
Symptoms 
Severity 
None 
Grade 1  
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially life-
threatening) 
Injection Site AEs (Local AEs) 
Erythema (redness) 
< 25 mm 
25 - 50 mm 
51 - 100 mm 
> 100 mm 
Necrosis or 
exfoliative 
dermatitis  
Swelling 
< 25 mm 
25 - 50 mm and 
does not interfere 
with activity 
51 – 100 mm or 
interferes with 
activity 
> 100 mm or 
prevents daily 
activity  
Necrosis 
Pain 
None 
Does not 
interfere with 
activity 
Repeated use of 
non-narcotic pain 
reliever for more 
than 24 hours or 
interferes with 
activity 
Any use of 
narcotic pain 
reliever or 
prevents daily 
activity 
Results in a visit 
to emergency 
room (ER) or 
hospitalization 
Solicited Systemic AEs 
Fever (ºC or ºF) 
 
< 38.0 ºC 
< 100.4 ºF 
38.0 - 38.4 ºC 
100.4 - 101.1 ºF 
38.5 - 38.9 ºC 
101.2 - 102.0 ºF 
39.0 - 40.0 ºC 
102.1 - 104.0 ºF 
> 40.0 ºC 
> 104.0 ºF 
Headache 
None 
No interference 
with activity 
Repeated use of 
non-narcotic pain 
reliever for more 
than 24 hours or 
some interference 
with activity 
Significant; any 
use of narcotic 
pain reliever or 
prevents daily 
activity 
Results in a visit 
to emergency 
room (ER) or 
hospitalization 
Fatigue  
None 
No interference 
with activity  
Some interference 
with activity  
Significant; 
prevents daily 
activity  
Results in a visit 
to emergency 
room (ER) or 
hospitalization 
Muscle aches 
None 
No interference 
with activity  
Some interference 
with activity  
Significant; 
prevents daily 
activity  
Results in a visit 
to emergency 
room (ER) or 
hospitalization 
Joint aches, chills, 
feeling of general 
discomfort or 
uneasiness (malaise), 
swelling in the axilla, 
swelling in the neck  
None 
No interference 
with activity 
Some interference 
with activity not 
requiring medical 
intervention  
Prevents daily 
activity and 
requires medical 
intervention  
Results in a visit 
to emergency 
room (ER) or 
hospitalization 
10.2.1.2 Adverse Events 
All spontaneous unsolicited AEs occurring within 28 days after vaccination will be reported in 
the “Adverse Event” screen in the subject’s eCRF, irrespective of intensity or whether or not 
they are considered to be vaccination-related. Thereafter, from Day 29 to the end of the study, 
SAEs, AEs leading to withdrawal, AESIs, and NOCDs will be monitored and reported in the 
eCRF. 

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The intensity of unsolicited AEs will be graded as: mild (1), moderate (2), severe (3) or 
potentially life threatening (4), according to the FDA Guidance for Industry [FDA 2007]. Their 
causal relationship with the study vaccine will be assessed by the Investigator (definitely not 
related, probably not related, possibly related, probably related or definitely related); see 
Section 13.1.9 for a definition of these causal relationships.  
The Investigator should assess unsolicited AEs and determine if any meet the criteria for SAE.  
Any unsolicited AEs that meet the criteria for SAE should be reported to the Sponsor within 
24 hours (Section 13.1.6) and entered as an SAE in the eCRF. 
10.2.1.3 Clinical Laboratory Tests 
Blood samples for biochemistry and haematology, HIV, Hepatitis B and Hepatitis C markers in 
serum, and urine samples for urinalysis will be collected according to the Time and Events 
Schedule (see Table 1). Any laboratory result outside of the testing laboratory’s normal range 
will be classified as ‘clinically significant’ (CS) or ‘not clinically significant’ (NCS) by the site 
Investigator, with appropriate documentation. Any laboratory test performed at screening with a 
value outside the normal range may be repeated (prior to vaccination) at the discretion of the 
Investigator. Repeated tests will be considered the Baseline results. 
The Investigator must review the laboratory reports, document this review, and record any 
clinically relevant changes occurring during the study in the source documents. The tests to be 
performed by the laboratory are presented in Table 7. 
Table 7 Clinical Laboratory Tests 
Biochemistry (serum): 
Sodium 
Alkaline phosphatase 
Potassium 
Alanine transferase (ALT) 
Urea 
Aspartate transferase (AST) 
Creatinine 
Gamma glutamyltransferase (GGT) 
Glucose 
Cholesterol (total, HDL, LDL) 
Bilirubin (total) 
Triglyceride 
Albumin 
Chloride 
Total protein 
Calcium 
 
Phosphorus 
Haematology: 
Haemoglobin 
Mean cell haemoglobin (MCH) 
Hematocrit  
Mean cell concentration (MCHC) 
Red blood cells 
Mean cell volume (MCV) 
Platelets 
Lymphocytes 
Mean platelet volume (MPV) 
Monocytes 
White cell count (total, WBC) 
Eosinophils 
Neutrophils 
Basophils 

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Serology: 
HIV 
Hepatitis B 
Hepatitis C 
 
Urinalysis: 
Macroscopic examination (color, aspect) 
Glucose 
pH 
Protein 
Specific gravity 
Blood 
All protocol required safety laboratory parameters are defined in study-specific documentation. 
10.2.1.4 Vital Signs 
Vital signs measurements (resting BP, HR, and OT) will be performed as part of screening 
procedures (prior to eligibility assessment on Day 0) and after the post-vaccination surveillance 
period. 
OT will be collected in degrees Celsius or Fahrenheit using a digital thermometer by the 
Sponsor. The OT measurement should not be collected immediately following consumption of a 
hot or cold beverage or after smoking. 
BP will be taken after the subject has been in a seated position as per the site’s standard 
procedure. BP should be taken by cuff (manual or automated are both acceptable). BP and HR 
may be repeated once if judged necessary. All measurements (including any repeats) will be 
recorded in the source documents. 
10.2.1.5 Physical Examinations 
A limited physical examination will be performed by the Investigator (or sub-Investigator) as 
part of screening procedures and on Day 0 (prior to eligibility assessment) and Day 3. 
History/symptom-directed physical examinations may be performed at any other study visits if 
1) new complaints or concerns are raised by either the study subject or study staff and 2) deemed 
to be necessary by the Investigator. 
10.2.2 Safety Endpoints 
10.2.2.1 Primary Endpoints 
x Occurrences, intensity, and relationship to vaccination of immediate AEs (30 minutes 
post-vaccination); 
x Occurrences and intensity of solicited local and systemic AEs (for seven days following 
study vaccine administration); 
x Occurrences, intensity, and relationship of unsolicited AEs for 28 days following study 
vaccine administration; 
x Number and percentage of subjects with normal and abnormal, clinically significant urine, 
haematological and blood biochemistry values, and urinalysis at Days 0, 3, and 28; 

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x Occurrences of SAEs, AEs leading to withdrawal, AESIs, MAAEs, NOCDs, and deaths up 
to Day 28; 
x Occurrences of SAEs, AEs leading to withdrawal, AESIs, MAAEs, NOCDs, and deaths 
from Day 29 up to Day 182; 
x Occurrences of SAEs, AEs leading to withdrawal, AESIs, MAAEs, NOCDs, and deaths 
from Day 183 up to the end of the study (Day 365). 
10.2.2.2 Secondary Endpoints 
x Occurrences, intensity, and relationship to vaccination of immediate AEs (30 minutes post-
vaccination), stratified by prior influenza vaccination status, if >25% of the enrolled 
subjects have received a standard influenza vaccine during the 12 months prior to study 
vaccination; 
x Occurrences and intensity of solicited local and systemic AEs (for seven days following 
study vaccine administration), stratified by prior influenza vaccination status, if >25% of 
the enrolled subjects have received a standard influenza vaccine during the 12 months prior 
to study vaccination; 
x Occurrences, intensity, and relationship of unsolicited AEs for 28 days following study 
vaccine administration, stratified by prior influenza vaccination status, if >25% of the 
enrolled subjects have received a standard influenza vaccine during the 12 months prior to 
study vaccination; 
x Number and percentage of subjects with normal and abnormal, clinically significant urine, 
haematological and blood biochemistry values, and urinalysis at Days 0, 3, and 28, 
stratified by prior influenza vaccination status, if >25% of the enrolled subjects have 
received a standard influenza vaccine during the 12 months prior to study vaccination; 
x Occurrences of SAEs, AEs leading to withdrawal, AESIs, MAAEs, NOCDs, and deaths up 
to Day 28, stratified by prior influenza vaccination status, if >25% of the enrolled subjects 
have received a standard influenza vaccine during the 12 months prior to study vaccination; 
x Occurrences of SAEs, AEs leading to withdrawal, AESIs, MAAEs, NOCDs, and deaths 
from Day 29 up to Day 182, stratified by prior influenza vaccination status, if >25% of the 
enrolled subjects have received a standard influenza vaccine during the 12 months prior to 
study vaccination; 
x Occurrences of SAEs, AEs leading to withdrawal, AESIs, MAAEs, NOCDs, and deaths 
from Day 183 up to the end of the study (Day 365), stratified by prior influenza vaccination 
status, if >25% of the enrolled subjects have received a standard influenza vaccine during 
the 12 months prior to study vaccination. 

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10.3 Immunogenicity 
10.3.1 Immunogenicity Evaluations 
Immunogenicity will be evaluated by the humoral immune response induced in subjects, using 
the HI assay on Days 0, 28, 182, and 365 and using the MN assay on Days 0 and 28.  
The blood samples for immunogenicity will be analyzed in one or more central laboratories; 
information on processing and the central laboratories will be provided in the study-specific 
documentation. 
10.3.2 Immunogenicity Endpoints 
Unless otherwise mentioned, point estimates and 95 % CI will be calculated for all 
immunogenicity endpoints and responses in the adjuvanted QVLP recipients will be compared 
with the active comparator groups using descriptive statistics. 
10.3.2.1 Primary Endpoint 
x HI antibody response induced by adjuvanted and unadjuvanted QVLP and Fluzone HD 
Quad against the homologous influenza strains on Day 28, compared to Day 0 values, will 
be analyzed as follows: 
x 
GMTs of HI antibody on Days 0 and 28; 
x 
SC rate: the proportion of subjects in a given treatment group with either a  4-fold 
increase in reciprocal HI titers between Day 0 and Day 28 or a rise of undetectable HI 
titer (i.e. < 10) pre-vaccination (Day 0) to an HI titer of  40 on Day 28; 
x 
SP rate: the proportion of subjects in a given treatment group attaining a reciprocal HI 
titer of  40 on Day 28 (the percentage of vaccine recipients with a serum HI titer of at 
least 1:40 following vaccination); 
x 
GMFR: the geometric mean of the ratio of GMTs (Day 28/Day 0). 
10.3.2.2 Secondary Endpoints 
x MN antibody response induced by adjuvanted and unadjuvanted QVLP and Fluzone HD 
Quad against the homologous influenza strains on Day 28, compared to Day 0 values, will 
be analyzed as follows: 
x 
GMTs of MN antibody on Days 0 and 28; 
x 
SC rate: the proportion of subjects in a given treatment group with either a  4-fold 
increase in reciprocal MN titers between Day 0 and Day 28 or a rise of undetectable MN 
titer (i.e. 7.1) pre-vaccination (Day 0) to an MN titer of  28.3 at Day 28 post-
vaccination; 
x 
GMFR: the geometric mean of the ratio of GMTs (Day 28/Day 0). 

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x HI antibody response induced by adjuvanted and unadjuvanted QVLP and Fluzone HD 
Quad against the heterologous influenza strains on Day 28, compared to Day 0 values. HI 
antibody titers will be analyzed as follows: 
x 
GMTs of HI antibody on Days 0 and 28; 
x 
SC rate: the proportion of subjects in a given treatment group with either a  4-fold 
increase in reciprocal HI titers between Day 0 and Day 28 or a rise of undetectable HI 
titer (i.e. < 10) pre-vaccination (Day 0) to an HI titer of  40 on Day 28; 
x 
SP rate: the proportion of subjects in a given treatment group attaining a reciprocal HI 
titer of  40 on Day 28 (the percentage of vaccine recipients with a serum HI titer of at 
least 1:40 following vaccination); 
x 
GMFR: the geometric mean of the ratio of GMTs (Day 28/Day 0). 
x HI antibody response (against homologous and heterologous influenza strains) and MN 
antibody response (against homologous influenza strains) induced by adjuvanted and 
unadjuvanted QVLP and Fluzone HD Quad on Day 28, compared to Day 0 values, 
stratified by prior influenza vaccination status, if >25% of the enrolled subjects have 
received a standard influenza vaccine during the 12 months prior to study vaccination; 
x Durability of antibody responses 6 months post-vaccination, as determined by HI antibody 
responses induced by adjuvanted and unadjuvanted QVLP and Fluzone HD Quad against 
the homologous influenza strains on Day 182, compared to Day 0 values.  
x 
HI antibody titers will be analyzed as follows: 
x 
GMTs of HI antibody on Day 182; 
x 
SC rate: the proportion of subjects in a given treatment group with either a  4-fold 
increase in reciprocal HI titers between Day 0 and Day 182 or a rise of undetectable HI 
titer (i.e. < 10) pre-vaccination (Day 0) to an HI titer of  40 on Day 182; 
x 
SP rate: the proportion of subjects in a given treatment group attaining a reciprocal HI 
titer of  40 on Day 182 (the percentage of vaccine recipients with a serum HI titer of at 
least 1:40 following vaccination); 
x 
GMFR: the geometric mean of the ratio of GMTs (Day 182/Day 0). 
x Durability of antibody responses 12 months post-vaccination, as determined by HI antibody 
responses induced by adjuvanted and unadjuvanted QVLP and Fluzone HD Quad against 
the homologous influenza strains on Day 365, compared to Day 0 values.  
x 
HI antibody titers will be analyzed as follows: 
x 
GMTs of HI antibody on Day 365; 
x 
SC rate: the proportion of subjects in a given treatment group with either a  4-fold 
increase in reciprocal HI titers between Day 0 and Day 365 or a rise of undetectable HI 
titer (i.e. < 10) pre-vaccination (Day 0) to an HI titer of  40 on Day 365; 
x 
SP rate: the proportion of subjects in a given treatment group attaining a reciprocal HI 
titer of  40 on Day 365 (the percentage of vaccine recipients with a serum HI titer of at 
least 1:40 following vaccination); 

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x 
GMFR: the geometric mean of the ratio of GMTs (Day 365/Day 0); 
11 SUBJECT COMPLETION/WITHDRAWAL 
11.1 Temporary Contraindications 
An exclusion criterion that renders subjects ineligible for the study may be temporary in nature: 
x Acute disease defined as presence of any moderate or severe acute illness with or without a 
fever within 48 hours prior to vaccination.  
If, on Day 0, a subject is considered ineligible due to one of these “temporary contraindications”, 
the subject should be considered as a screening failure. Following the resolution of such 
conditions, a subject may be rescreened (including the informed consent process) under a new 
number and, if considered eligible by the Investigator, be enrolled in the study. 
11.2 Screening Failures 
Screening failures are subjects who have signed the study-specific ICF but are not eligible for 
enrollment (subjects who were not randomized), due to failure on one or more of the inclusion or 
exclusion criteria or because the subject withdrew consent prior to randomization.  
Recording of screening failures will be documented in the study records maintained at the 
participating clinical sites and recorded in the IRT system. Screen failures will not receive a 
safety follow-up. Any subjects who are considered as a screening failure should be indicated as 
such. A screening failure subject can be rescreened (under a new number). If the subject is 
rescreened (including the informed consent process), a new subject number will be allocated. 
11.3 Removal of Subjects from Treatment or Assessment 
Subjects will be advised that they are free to withdraw from the study at any time without 
prejudice to their future medical care by the physician or the institution. Subjects who withdraw 
or are withdrawn from the study after vaccination will not be replaced. 
Every reasonable effort will be made to ensure that each subject complies with the protocol and 
completes all study visits. However, a subject may withdraw or be withdrawn from participation 
in the study if: 
x The subject withdraws consent; 
x The subject is lost to follow-up; 
x The subject is incarcerated or incapacitated during the conduct of the clinical study; 
x The subject has moved away from the study area and can no longer fulfill the terms of their 
participation in the clinical study; 
x The subject displays non-compliance to the terms of their participation in the clinical study 
(based on Investigator’s or Medicago’s [or its designee’s] opinion); 

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x The Investigator has lost confidence in the subject’s ability to adhere to the terms of their 
participation in the clinical study (based on Investigator’s opinion); 
x Safety reasons as judged by the Investigator and/or Medicago (or its designee); 
x Medicago or the regulatory authority(ies) terminates the clinical study. 
Withdrawal subjects will be those who leave the study before Day 365, for whatever reason; 
withdrawal subjects will not be replaced. Any subject who withdraws consent from the study 
will be asked to visit the clinical site within two weeks of withdrawal, if the subject agrees. The 
procedures performed for the final assessment will comprise of those for the Day 365 visit, if 
permitted by the subject. All withdrawal subjects must be reported to Medicago (and/or its 
designee). The reason for withdrawal should be documented in the subjects’ records and in the 
appropriate section of the eCRF. The eCRF must be completed up to and including the time of 
the drop-out/final assessment. 
11.3.1 Follow-up of Discontinuations 
All subjects who receive a study vaccine will be followed for safety until the end of the study, if 
permitted by the subject. 
11.3.2 Lost to Follow-up Procedures 
Every attempt will be made to contact study subjects who are lost to follow-up. At least three 
contacts will be attempted and recorded in the source documents. As a last resort, one registered 
letter requesting contact with the site will be sent to any subject with whom the clinic staff no 
longer has contact. All attempts at contact will be documented in the subject’s source documents. 
11.4 Interruption of the Study 
The Investigator (in consultation with Medicago [or its designee]), Medicago, or Regulatory 
Authorities may interrupt or terminate this study for any reason. In addition, the IDMC may 
interrupt or halt the study for safety reasons (refer to Section 13.1.12). The Investigator will 
immediately, on discontinuance of the clinical study at the clinical site, inform both the study 
subjects and the Institutional Review Board (IRB) responsible for the study of the 
discontinuance, provide them with reasons for the discontinuance and advise them in writing of 
any potential health risks to the subjects themselves or to other persons. It is Medicago’s (or its 
designee’s) responsibility to report discontinuance of the study to the local regulatory agencies 
within the appropriate timeframe, providing them with the reasons for the discontinuance and 
advising them in writing of any potential health risks to the study subjects or to other persons. 
Medicago (or its designee) must then inform the Investigator that the appropriate notifications 
were done. 

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12 STATISTICAL METHODS 
A general description of the statistical methods used to analyze the safety and immunogenicity 
data is outlined below. Complete details will be provided in the SAP, which will be finalized 
prior to screen the first subject. 
All descriptive and inferential statistical analyses will be performed using Statistical Analysis 
System® (SAS®) software (version 9.4 or higher). 
12.1 Analysis Populations 
12.1.1 Safety Analysis Set 
The SAS is defined as all subjects who received either the adjuvanted QVLP or the active 
comparators. All safety analysis will be performed using the SAS, according to the treatment the 
subjects actually received. 
12.1.2 Intention-To-Treat Set 
The ITT set will consist of all subjects who were randomized in the study. Subjects who received 
the wrong treatment will be analyzed as randomized. 
12.1.3 Per Protocol Set 
The per protocol (PP) set will consist of a subset of subjects with a Day 0 and any post-
vaccination immunogenicity assessment who completed the study with no major protocol 
deviations related to subject eligibility, the ability to develop a valid immune response, 
prohibited medication use, or the immunogenicity analyses; and who received QVLP or the 
active comparators. For the Day 28 analysis, this should include the subjects who received the 
vaccine dose and had Day 0 and Day 28 immunogenicity sample collections. For the Day 182 
analysis, this should include the subjects who received the vaccine dose and had Day 0 and 
Day 182 immunogenicity sample collections. For the Day 365 analysis, this should include the 
subjects who received the vaccine dose and had Day 0 and Day 365 immunogenicity sample 
collections. Subjects who had blood samples for immunogenicity taken outside of the time 
window for blood sample collection are to be excluded from the PP set for the specific visit. 
Major protocol deviations will be identified and documented during a blinded data review prior 
to database lock and confirmed at the time of database lock. Subjects who received the wrong 
treatment, but for whom the treatment received can be unequivocally confirmed, will be 
analyzed as treated, provided they have no other deviations that compromise their data. 
The analyses of all immunogenicity endpoints will be performed using the PP set and the 
ITT set. The analysis in the PP set will be considered the primary analysis for these objectives in 
order to collect information regarding the immunogenicity responses that most closely reflect the 
scientific model underlying the protocol. The ITT set will be used as sensitivity analysis. 

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12.2 Sample Size Determination 
The sample size up to approximately 120 subjects with 40 subjects in each treatment group will 
make it possible to perform the initial evaluation of vaccine immunogenicity and detect gross 
differences in rates of adverse events. The sample size is not large enough to detect all types of 
adverse reactions, including less frequent or rare events. The objective of this study is to quantify 
the type, percentage, intensity, duration, and relationship of common post-vaccination safety 
events to determine if they differ clinically among the treatment groups. 
12.3 Day 28 and Day 182 Data Analyses 
Data analyses will be performed after the last subject has completed Day 28 assessments and 
Day 182 assessments; selected tables, listings and figures (as applicable) will be generated 
according to the SAP, by the third-party statistical team (see Section 6.2). The results of the 
interim analysis will be confidential and strictly limited to the authorized staff members (see 
Section 6.2). Moreover, these results will allow discussions of the clinical data to inform study 
design decisions of the subsequent study, without having to wait until after the end of the follow-
up period for study completion.  
12.4 Baseline and Subject Disposition 
Demographic data and influenza immunization history will be presented in listings and 
summarized by treatment. Continuous variables including age, weight, height, and BMI will be 
summarized with mean, median, standard deviation, minimum, and maximum. Count and 
percentage of subjects will be presented for categorical variables such as sex, race, ethnicity, and 
immunization history. 
The number of subjects in different study disposition statuses will be summarized by number 
and, when applicable, percentage (based on vaccinated subjects). Subjects’ 
completion/discontinuation status will be listed (including subject identifier, date of 
completion/early discontinuation and, for those who discontinued early, the specific reason(s) for 
discontinuation). 
12.5 Safety Analyses 
The safety endpoints are defined in Section 10.2.2. 
12.5.1 Analysis of Primary Endpoints 
The primary safety endpoints are defined in Section 10.2.2.1. 
The original terms used in the eCRFs by Investigators to identify AEs will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA®). All eCRF reported AEs with onset 
post-vaccination will be included in the safety analyses. 
Safety and tolerability endpoints (immediate AEs [30 minutes post-vaccination], solicited local 
and systemic AEs, unsolicited AEs, SAEs, AEs leading to subject withdrawal, AESIs, MAAEs, 
NOCDs, and deaths) will be summarized by treatment using descriptive statistics. 

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Laboratory (biochemical, haematological, and urine) data will be summarized by type of 
laboratory test. Reference ranges and markedly abnormal results will be used in the summary of 
laboratory data. Descriptive statistics will be calculated for each laboratory test at Baseline and at 
each scheduled timepoint (Day 3 and Day 28). Changes from Baseline results will be presented 
in pre- versus post-treatment cross tabulations (with classes for below, within, and above normal 
ranges). 
Special attention will be given to those subjects who die, who discontinue from the study due to 
an AE, who experience an SAE (e.g. summaries, listings, and narrative preparation may be 
provided, as appropriate), or who experience an AESI (see Section 13.1.3). 
Analyses of primary safety endpoints will include each group as a whole. For the following 
categories, AE information will also be presented by gender (male and female) and race 
(Caucasian or White; Black or African American; Asian) for the overall population (65 years of 
age and older): 
x Immediate solicited and unsolicited AEs up to 30 minutes after vaccination; 
x Solicited local and systemic AEs within Days 0 to 7; 
x Most frequent unsolicited AEs within 28 days after vaccination; 
x AESIs; 
x MAAEs; 
x SAEs; 
x AEs leading to death; 
x AEs leading to withdrawal. 
12.5.2  Analysis of Secondary Endpoints 
The secondary safety endpoints are defined in Section 10.2.2.2. 
The analysis of the secondary safety endpoints will be identical to the analysis of the primary 
safety endpoints (refer to Section 12.5.1) with the exception that the analysis will only include 
comparisons by prior influenza vaccination status, if >25% of the enrolled subjects have received 
a standard influenza vaccine during the 12 months prior to study vaccination.  For the following 
categories, AE information will also be presented by gender (male and female) and race 
(Caucasian or White; Black or African American; Asian) according to prior influenza 
vaccination status, if >25% of the enrolled subjects have received a standard influenza vaccine 
during the 12 months prior to study vaccination: 
x Immediate solicited and unsolicited AEs up to 30 minutes after vaccination; 
x Solicited local and systemic AEs within Days 0 to 7; 
x Most frequent unsolicited AEs within 28 days after vaccination; 
x AESIs; 
x MAAEs; 

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x SAEs; 
x AEs leading to death; 
x AEs leading to withdrawal. 
12.6 Immunogenicity Analyses 
12.6.1 Analysis of Primary Endpoint 
The primary immunogenicity endpoint is defined in Section 10.3.2.1.  
The following analyses for the HI assay (homologous strains) will be performed on the PP set: 
x GMT (Day 0 and Day 28): The point estimates and the corresponding two-sided 95 % CI 
by treatment group and strain will be calculated as the antilog of the mean and 95 % CI of 
log transformed titer values; 
x SC rate (Day 28): The point estimates and the corresponding two-sided 95 % CI for 
subjects achieving SC by treatment group and strain will be calculated and reported; 
x SP rate (Day 0 and Day 28): The point estimates and the corresponding two-sided 95 % CI 
for subjects achieving SP by treatment group and strain will be calculated and reported; 
x GMFR: the geometric mean of the ratio of GMTs (Day 28/Day 0). 
The GMFR will be derived by using ANCOVA to model the difference in the log of the titer 
values between Day 28 and Day 0, with treatment group as main effect and baseline titer as 
covariate.  
GMT for HI will be compared between treatment groups using the analysis of variance 
(ANOVA) model. GMFR for HI will be compared using the ANCOVA model. For SC rate and 
SP rate, Fisher’s exact tests or chi square tests will be used to compare between the treatment 
groups.  
Analyses of primary immunogenicity endpoint will include each group as a whole.  
The analyses of the primary immunogenicity endpoints will also be performed using the ITT set. 
12.6.2 Analysis of Secondary Endpoints 
The secondary immunogenicity endpoints are defined in Section 10.3.2.2.  
The following analyses for the MN assay (homologous strains) will be performed on the PP set: 
x GMT (Day 0 and Day 28): The point estimates and the corresponding two-sided 95 % CI 
by treatment group and strain will be calculated as the antilog of the mean and 95 % CI of 
log transformed titer values; 
x SC rate (Day 28): The point estimates and the corresponding two-sided 95 % CI for 
subjects achieving SC by treatment group and strain will be calculated and reported; 
x GMFR: the geometric mean of the ratio of GMTs (Day 28/Day 0). 

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The following analyses for the HI assay (heterologous strains) will be performed on the PP set: 
x GMT (Day 0 and Day 28): The point estimates and the corresponding two-sided 95 % CI 
by treatment group and strain will be calculated as the antilog of the mean and 95 % CI of 
log transformed titer values; 
x SC rate (Day 28): The point estimates and the corresponding two-sided 95 % CI for 
subjects achieving SC by treatment group and strain will be calculated and reported; 
x SP rate (Day 0 and Day 28): The point estimates and the corresponding two-sided 95 % CI 
for subjects achieving SP by treatment group and strain will be calculated and reported; 
x GMFR: the geometric mean of the ratio of GMTs (Day 28/Day 0). 
The GMFR will be derived by using ANCOVA to model the difference in the log of the titer 
values between Day 28 and Day 0, with treatment group as main effect and baseline titer as 
covariate.  
The durability of the HI antibody responses will be evaluated up to 6 months post-vaccination. 
The following analyses for the HI assay will be performed on the PP set:  
x GMT (Day 182): The point estimates and the corresponding two-sided 95 % CI by 
treatment group and strain will be calculated as the antilog of the mean and 95 % CI of log 
transformed titer values; 
x SC rate (Day 182): The point estimates and the corresponding two-sided 95 % CI for 
subjects achieving SC by treatment group and strain will be calculated and reported; 
x SP rate (Day 182): The point estimates and the corresponding two-sided 95 % CI for 
subjects achieving SP by treatment group and strain will be calculated and reported; 
x GMFR: the geometric mean of the ratio of GMTs (Day 182/Day 0). 
The GMFR will be derived by using ANCOVA to model the difference in the log of the titer 
values between Day 182 and Day 0, with treatment group as main effect and baseline titer as 
covariate. 
The durability of the HI antibody responses will be evaluated up to 12 months post-vaccination. 
The following analyses for the HI assay will be performed on the PP set:  
x GMT (Day 365): The point estimates and the corresponding two-sided 95 % CI by 
treatment group and strain will be calculated as the antilog of the mean and 95 % CI of log 
transformed titer values; 
x SC rate (Day 365): The point estimates and the corresponding two-sided 95 % CI for 
subjects achieving SC by treatment group and strain will be calculated and reported; 
x SP rate (Day 365): The point estimates and the corresponding two-sided 95 % CI for 
subjects achieving SP by treatment group and strain will be calculated and reported; 
x GMFR: the geometric mean of the ratio of GMTs (Day 365/Day 0). 

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The GMFR will be derived by using ANCOVA to model the difference in the log of the titer 
values between Day 365 and Day 0, with treatment group as main effect and baseline titer as 
covariate. 
GMTs for HI and MN (at Days 0 and 28 only) will be compared between treatment groups using 
the ANOVA model. GMFRs for HI and MN (at Days 0 and 28 only) will be compared using the 
ANCOVA model. For SC rate (HI and MN [at Day 28 only]) and SP rate (HI only), Fisher’s 
exact tests or chi square tests will be used to compare between the treatment groups. 
The analyses for the HI assay (homologous strains) will include comparisons by prior influenza 
vaccination status, if >25% of the enrolled subjects have received a standard influenza vaccine 
during the 12 months prior to study vaccination.  
The analyses for the HI assay (heterologous strains) and the MN assay (homologous strains, at 
Days 0 and 28 only) will include each group as a whole as well as comparisons by prior 
influenza vaccination status, if >25% of the enrolled subjects have received a standard influenza 
vaccine during the 12 months prior to study vaccination.  
The analyses of the secondary immunogenicity endpoints will also be performed using the 
ITT set. 
13 ADVERSE EVENT REPORTING 
Timely, accurate, and complete reporting and analysis of safety information from clinical studies 
are crucial for the protection of subjects, Investigators, and the Sponsor, and are mandated by 
regulatory agencies worldwide. 
13.1 Definitions 
13.1.1 Serious Adverse Events 
An SAE is any untoward medical occurrence (whether or not considered to be related to the 
study vaccine) that, at any dose: 
x Results in death; 
x Is life-threatening (at the time of the event); 
Note: the term “life-threatening” in the definition of an SAE refers to an event that put the 
subject at risk of death at the time of the event; it does not refer to an event that hypothetically 
might have caused death if it were more severe; 
x Requires inpatient hospitalization ( 24 hours) or prolongation of existing hospitalization 
(elective hospitalizations/procedures for pre-existing conditions that have not worsened are 
excluded); 
x Results in persistent or significant disability/incapacity; 
x Is a congenital abnormality/birth defect; 
x Is another medically important event. 

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Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
appropriate in other situations, such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization but that may jeopardize the subject’s health 
or may require an intervention to prevent one of the other outcomes listed in the definition 
above. These events should be considered serious. Examples of such events are intensive 
treatment in an emergency room for allergic bronchospasm, blood dyscrasias, or convulsions that 
do not result in hospitalization or the development of drug dependency or drug abuse. See 
Section 13.1.6 for initial SAE reporting by the Investigator. 
13.1.2 Adverse Events 
An AE or adverse experience is defined as any untoward medical occurrence in a subject or 
clinical investigation subject who was administered a pharmaceutical product, with or without a 
causal relationship with the treatment. An AE can be any favorable and unintended sign, 
symptom, or disease temporally associated with the use of a medicinal product, whether or not 
related to a medicinal product. 
Information such as the date and time of onset and resolution (duration), intensity (defined 
below), seriousness, any required treatment or action taken, outcome, relationship to the 
investigational vaccine, and whether the AE caused withdrawal from the study will be collected. 
The intensity of all AEs will be graded as mild (1), moderate (2) severe (3), or potentially life 
threatening (4), according to the FDA Guidance for Industry: Toxicity Grading Scale for Healthy 
Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials [FDA 2007] for 
the events covered in the guidance and the following definitions for all other events: 
Mild (Grade 1): 
The AE is easily tolerated and does not interfere with usual 
activity; 
Moderate (Grade 2): 
The AE interferes with daily activity, but the subject is still able 
to function; 
Severe (Grade 3): 
The AE is incapacitating and the subject is unable to work or 
complete usual activity; 
Potentially life-threatening 
(Grade 4): 
The AE is likely to be life-threatening if not treated in a timely 
manner. 
Note: According to the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult 
and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials [FDA 2007]: 
“Nonetheless, we believe that categorization or grading of data as outlined in this document 
is supplementary to and should not replace full and complete data analysis. These guidelines 
for toxicity grading scales are primarily intended for healthy adult and adolescent 
volunteers.” and “Toxicity grading scales for laboratory abnormalities should consider the 
local laboratory reference values when the parameter limit values are defined. The 
characterization of laboratory parameters among some populations of healthy adults and 
adolescents may require the exercise of clinical judgment, for example, consideration of the 
potential for ethnic differences in white blood cell (WBC) counts or gender differences in 
creatine phosphokinase (CPK) values.” 

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The Investigator will be instructed to closely monitor each subject who experiences an AE 
(whether ascribed to the investigational product or not) until the outcome of the AE has been 
determined. 
If any of the solicited local or systemic AEs persist beyond Day 7, these will also be recorded as 
unsolicited AEs. In this case, the AE start will be set as eight days post-vaccination. The subject 
will be requested to note when the AE resolves and to report this information to the Investigator 
or clinic staff at the next visit at the clinical site or contact. 
The clinical importance of AEs will be determined based upon the Investigator’s judgment. The 
Investigator must ensure that any sample obtained to follow-up on an AE is properly labeled and 
stored. The Investigator and others responsible for care of the subjects should institute any 
supplementary investigations of significant AEs based on the clinical assessment of the likely 
causative factor. This may include seeking the opinion of a specialist in the field of the AE. 
All unsolicited AEs occurring within 28 days after vaccination must be reported in the “Adverse 
Event” screen in the subject’s eCRF, irrespective of intensity or whether or not they are 
considered to be vaccination-related. Thereafter, from Day 29 through to Day 365, SAEs, AEs 
leading to withdrawal, AESIs, MAAEs, and NOCDs (see Section 13.1.4 for definition) will be 
monitored and reported in the eCRF. Additional details on eCRF entries can be found in the 
eCRF completion guidelines. 
13.1.2.1 Medically Attended Adverse Events 
Medically attended adverse events are defined as symptoms or illnesses requiring hospitalization, 
or emergency room visit, or visit to/by a health care provider. 
13.1.3 Adverse Events of Special Interest 
13.1.3.1 Adverse Events of Special Interest for QVLP 
13.1.3.1.1 Hypersensitivity Reactions 
In the eight studies completed to date, all reported events were monitored for a possible 
hypersensitivity component (events were searched using both narrow and broad standardized 
MedDRA® queries). Based on the data available so far, there is no definitive evidence of 
anaphylaxis associated with use of QVLP in humans. However, one subject who received QVLP 
experienced a possible, truncated anaphylactic reaction assessed as possibly related to the 
vaccine by the Investigator. Also, a small number of subjects had potential hypersensitivity 
reactions judged to be related to vaccine administration (no more than 0.5 % of subjects in any 
given VLP treatment group experienced one of these events) and these events were distributed 
fairly evenly among treatment groups, including the placebo and the active comparator groups. 
However, since severe reactions are considered to be an important potential risk (based on the 
theoretical risk that using plants for the production of biotherapeutics may induce 
hypersensitivity) the Sponsor will continue to require that appropriate medical treatment and 
supervision are available to manage any possible anaphylactic reactions. Further, to collect 

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additional data on these events, Medicago will closely monitor and assess anaphylaxis and severe 
allergic reactions (grade 3 and above) assessed as related to the Investigational product as AESIs.  
13.1.3.2 Adverse Events of Special Interest for AS03 
13.1.3.2.1 Narcolepsy 
An increased risk of narcolepsy (a lifelong disease causing an overwhelming daytime drowsiness 
and sudden attacks of sleep) was observed in some individuals after vaccination with a flu 
vaccine containing AS03 (called Pandemrix™) during the H1N1 pandemic in 2009-2010. This 
study vaccine contains AS03. A similar risk of narcolepsy was not identified with other vaccines 
containing AS03. Currently available data suggest that the cases of narcolepsy seen immediately 
following the 2009-2010 pandemic in some people were most likely triggered by a reaction in 
those people to a protein from the flu virus itself which was used to manufacture the 
Pandemrix™ vaccine. Research is continuing to assess whether either of the main components of 
the 2009-2010 flu pandemic vaccine (e.g., the viral proteins in the form used in the vaccine or 
the AS03 adjuvant) may have contributed to the reaction.  
Safety signal of narcolepsy after exposure to QVLP with adjuvant AS03 will be closely 
monitored by retrieving data for this AESI using MedDRA PT Narcolepsy and analyzing 
available data via Medicago’s safety governance process for any potential signal. 
13.1.3.2.2 Potential Immune-Mediated Diseases and Other AESI as Listed in Section 19.5 
These important potential risks remain “theoretical” as they were for other vaccines containing 
adjuvants and hence will be collected as AESIs. Potential immune-mediated diseases (pIMDs) 
are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic 
disorders of interest which may or may not have an autoimmune aetiology. Adverse events that 
need to be recorded and reported as pIMDs include those listed in Section 19.5. 
However, the Investigator will exercise their medical and scientific judgement in deciding 
whether other diseases have an autoimmune origin (that is pathophysiology involving systemic 
or organ-specific pathogenic autoantibodies) and should also be recorded as a pIMD. 
When there is enough evidence to make any of the diagnoses mentioned in Section 19.5, the AE 
must be reported as a pIMD. Symptoms, signs or conditions which might (or might not) 
represent the above diagnoses, should be recorded and reported as AEs but not as pIMDs until 
the final or definitive diagnosis has been determined, and alternative diagnoses have been 
eliminated or shown to be less likely. 
In order to facilitate the documentation of pIMDs in the eCRF, a pIMD standard questionnaire 
and a list of preferred terms (PTs) and PT codes corresponding to the above diagnoses will be 
available to Investigators at study start. 
Once a pIMD is diagnosed (serious or non-serious) in a study subject, the Investigator (or 
designate) must complete, date and sign an Adverse Events Report Form. 

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13.1.4 New Onset of Chronic Disease 
In the context of this study, all NOCDs that may plausibly have an allergic, autoimmune or 
inflammatory component are to be reported. Plausibility should be interpreted broadly however; 
the only clear exceptions are degenerative conditions such as osteoarthritis, age-related 
physiologic changes (e.g. benign prostatic hypertrophy) and life-style diseases (e.g. alcohol-
associated cirrhosis, bronchitis in a smoker, etc.). In this context, most cancers, cardiac 
conditions and kidney diseases should be reported. 
NOCDs will be collected from vaccination on Day 0 to Day 365 and reported as an AE or SAE, 
as applicable. 
13.1.5 Expectedness of an Adverse Drug Reaction 
An “unexpected” adverse reaction is one in which the nature or severity of the event is not 
consistent with information in the current version of the IB. Expedited reporting to the regulatory 
authorities is required if an SAE occurs that is both unexpected and considered possibly, 
probably, or definitely related to the study vaccine. 
13.1.6 Initial SAE Reporting by the Investigator 
Details on safety reporting are defined in study-specific documentation, including SAE 
processing, country-specific reporting requirements, regulatory unblinding, roles and 
responsibilities of different stake holders, and contact details of personnel responsible for safety 
reporting. A brief summary of salient information is presented below. 
All post-vaccination SAEs and AESIs will be reported from the time of receiving the study 
vaccine on Day 0 through to the end of the study (final scheduled visit). The Investigator (or 
designee) must report, by e-mail, all SAEs and AESIs, whether considered related to the study 
vaccine or not to Medicago (or its designee) within 24 hours of the Investigator learning of the 
event. The Investigator must also complete the electronic SAE/AESI form in the electronic data 
capture (EDC) database within 24 hours of awareness of the event following the Electronic Case 
Report Form Completion Guidelines (eCCG). An automatic email notification will be sent to the 
Medicago Clinical Safety mailbox after the Investigator submits the electronic SAE/AESI form. 
If the EDC database is not available, the Investigator must complete, sign, and date the paper 
SAE/AESI report form, and send, via e-mail, a copy to the Medicago safety e-mail address 
(listed below) and the appropriate regional e-mail address, as required, within 24 hours of 
awareness of event. If the SAE/AESI paper reporting process is followed, the Investigator will 
need to enter the SAE/AESI information in the EDC system once available. 
Medicago Safety e-mail address: 
Medicago-ClinicalSafety@medicago.com 
 
 

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Sponsor Safety Contact: 
 
 
Serious AEs will be reported to the local (or contract) IRB by the Investigator according to the 
IRB’s policy and procedures. 
13.1.7 Follow-up Reporting by the Investigator 
All SAEs, regardless of causality, will be followed as described in Section 13.1.2. When 
appropriate, documentation of any medical tests or examinations performed will be provided to 
document resolution/stabilization of the event. 
13.1.8 Reporting of SAEs Occurring after Surveillance Period or Study Termination 
All SAEs occurring during the safety follow-up period will be followed until resolution or for a 
period of 30 days from the final subject’s visit (whichever occurs first), regardless of conclusion 
of the study. However, all related SAEs occurring during the safety follow-up period will be 
followed until resolution or stabilization. 
A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE detection 
period (post-Day 365). Active follow-up for AEs or SAEs will continue until Day 365 for all 
subjects. However, after Day 365, if the Investigator learns of any SAE, including death, at any 
time after a subject has been discharged from the study, and he/she considers the event to be 
reasonably related to the investigational product, the Investigator will promptly notify the 
Sponsor Safety Contacts for Reporting SAEs. These related SAEs will be followed until 
resolution or stabilization. 
13.1.9 Causal Relationship 
The Investigator must make the determination of relationship to the study vaccine for each 
unsolicited AE. The causal relationship of all solicited local and systemic AEs will be considered 
related. The Investigator should decide whether, in his/her medical judgment, there is a 
reasonable possibility that the event may have been caused by the investigational vaccine. If 
there is any valid reason, even if undetermined or untested, for suspecting a possible cause-and-
effect relationship between the investigational vaccine and the occurrence of the AE, then the AE 
should be considered “definitely related”, “probably related”, or “possibly related”. Otherwise, if 
no valid reason exists for suggesting a possible relationship, then the AE should be classified as 
“probably not related” or “definitely not related”. The following guidance should be followed: 
Definitely Not 
Related: 
The AE is clearly not related to the administration of the study vaccine. 
Another cause of the event is most plausible; and/or a clinically 
plausible temporal sequence is inconsistent with the onset of the event 
and the study vaccine administration; and/or a causal relationship is 
considered biologically implausible. 
PPD

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Probably Not 
Related: 
There is no medical evidence to suggest that the AE is related to the 
study vaccine. The event can be readily explained by the subject’s 
underlying medical condition or concomitant therapy or lacks a 
plausible temporal relationship to the study vaccine. 
Possibly Related: 
A direct cause and effect relationship between the study vaccine and the 
AE has not been demonstrated but there is a reasonable possibility that 
the event was caused by the study vaccine. 
Probably Related: 
There probably is a direct cause and effect relationship between the AE 
and the study vaccine. A plausible biologic mechanism and temporal 
relationship exist and there is no more likely explanation. 
Definitely Related: 
There is a direct cause and effect relationship between the AE and the 
study vaccine.  
AE outcomes will be classified as recovered/resolved, not recovered/not resolved, 
recovered/resolved with sequelae, recovering/resolving, or death. 
13.1.10 Reporting of SAEs to Health Authorities and IRB 
Medicago or its designee will be responsible for reporting SAEs that are deemed both possibly 
related to the study vaccine and considered to be unexpected (‘unexpected’ refers to events that 
do not appear in the package labeling or in the study vaccine IB) to the regulatory authorities in 
an expedited manner. 
The Investigator will be responsible for reporting the SAEs that meet IRB reporting requirements 
directly to the relevant ethics review board as soon as possible and will also provide the ethical 
review board with any safety reports prepared by Medicago or its designee. 
All SAEs that are suspected, unexpected serious adverse reactions (SUSARs) should be reported 
to regulatory authorities by phone or by facsimile transmission as soon as possible but, in no 
event, later than seven calendar days for deaths and life-threatening events, and 15 calendar days 
for other SAEs after Medicago's (or its designee’s) initial receipt of the information. These 
events should be followed to resolution, stabilization, or return to baseline, regardless of 
conclusion of the study. 
13.1.11 Independent Data Monitoring Committee 
The IDMC will consist of a multidisciplinary group of three clinicians and/or physicians and one 
biostatistician who will, collectively, have extensive experience in the use of vaccines for patient 
treatment and in the conduct and safety monitoring of randomized clinical trials.  
The IDMC will monitor the study conduct and review safety data at pre-defined times during the 
study for the purpose of providing recommendations to the Sponsor about whether: 
x subject vaccination at a dose level will continue; 
x subject vaccination at the next higher dose level will proceed;  
x the study will continue in the event of a pre-defined safety signal.  

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The IDMC review will ensure the ongoing safety of the subjects in the study and the scientific 
integrity of the study.
The IDMC will participate in 2 planned review meetings, as described in Section 13.1.12 and 
will be provided with an unblinded seven-day safety data summary (refer to Section 19.4 and 
further defined in the IDMC charter) for each review meeting. Additional review meetings may 
be scheduled with the IDMC, if deemed necessary by the IDMC or the Sponsor. 
13.1.12 Safety Review and Stopping Rules 
A review of seven-day safety data will be carried out after the vaccination of the first three 
subjects in each of the treatment groups to ensure ongoing safety of study subjects as well as 
maintaining study scientific integrity. The review will include safety data from the first three 
subjects in treatment groups 1 to 3 (as presented in Table 4) and will determine whether 
vaccination of the remaining subjects in these three treatment groups. IDMC reviews will detect 
any early negative trends in the subjects and may necessitate a decision to not administer the 
study vaccine to the remaining subjects. The vaccinations for the first three subjects in each 
treatment group will be staggered so that each vaccination must be performed at least 30 minutes 
apart. A phone call reminding study subjects to complete the diary will be made at Day 1 and 
Day 8 post-vaccination and the subjects will be asked to visit the clinical site on Day 3 for safety 
assessments. Early accumulated safety outcome data which will include all self-reported solicited 
local and systemic symptoms, any adverse and/or serious adverse events occurring following 
administration of the injection will be collected and tabulated.  
The IDMC will be provided the following unblinded seven-day solicited local and systemic AEs 
for the first three subjects enrolled in each of the three treatment groups: 
x Occurrences of erythema, swelling and pain at the injection site; 
x Occurrences of fever, headache, muscle aches, joint aches, fatigue, chills, and 
feelings of general discomfort or uneasiness;  
x Swelling in the axilla or neck; 
x Occurrence of any adverse or serious adverse events; 
x Concomitant medications, doctor or emergency room or hospital visits associated 
with an adverse event or serious adverse event. 
If the seven-day safety data summary (refer to Section 19.4) for the first three subjects in 
treatment groups 1 to 3 reviewed by the IDMC shows the safety of the vaccine (see Stopping 
rules below), the remaining subjects in treatment groups 1 to 3 will receive their vaccination. If 
the data does not show safety of the vaccine (see Stopping Rules below) for a particular 
treatment and the decision from the IDMC review is to stop further use of this treatment, then the 
following will apply: 
x Subjects administered this treatment will be followed to the end of the study for all safety 
and immunogenicity outcomes, if subject permits; 

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x Subjects originally planned to be administered this treatment will not be redistributed to the 
other treatment groups (i.e. the planned sample size for each treatment group will not 
change); 
x The study will continue in accordance with the protocol for the treatments deemed safe by 
the IDMC. 
Stopping Rules 
Safety monitoring of safety signals will be performed throughout the study. Stopping rules or 
conditions for stopping this clinical trial would occur if there was clear evidence of harm or 
harmful effects such as SAEs related to the treatment (study vaccine). An SAE which was 
thought to be unrelated to the study vaccine would not warrant stopping the trial.  
The following event(s) may result in a halt to the study, for further review and assessment of the 
event(s): 
x Any vaccine-related SAE in a subject for which causality cannot be attributed to 
another cause;  
x If 2 or more subjects in a single treatment group experience the same or similar 
event(s) that cannot be clearly attributed to another cause:  
o a Grade 3 or higher vaccine-related AE during the study; 
o a Grade 3 or higher vaccine-related vital sign(s) abnormality; 
o a Grade 3 or higher vaccine-related clinical laboratory abnormality. 
In the case that a pre-defined safety signal is met in any treatment group, subsequent dosing will 
result in at least a transient halt in the study to permit a complete evaluation of the reported 
event(s) and to consult an IDMC. A decision as to whether the study can progress as planned 
must be made and documented in the event of any safety signal. 
14 INVESTIGATIONAL PRODUCT INFORMATION 
14.1 Identity of Investigational Product 
The study vaccine QVLP is composed of recombinant H1, H3, and two B proteins 
(hemagglutinin) expressed as VLPs and will be administered with the adjuvant AS03. 
14.1.1 Study Vaccine Composition 
QVLP is a sterile transparent to opalescent colorless to slightly yellowish liquid suspension 
consisting of a mix of VLPs from four strains, each bearing the hemagglutinin of one of the 
recommended virus strains, in a phosphate buffered saline (PBS) solution (100 mM NaKPO4, 
150 mM NaCl) and 0.01 % polysorbate 80 at pH 7.4). 
AS03 is an established effective adjuvant that has been used in a licensed monovalent vaccine in 
the USA targeting H5N1 (Influenza A [H5N1] Virus Monovalent Vaccine, Adjuvanted). The 
adjuvant is a whitish to yellowish homogeneous milky liquid emulsion and it will be provided in 

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the original sterile vial container received from the manufacturer (GlaxoSmithKline). A 0.25 mL 
dose of AS03 represents one human dose. 
14.1.2 Active Comparators 
One of the two active comparators will be unadjuvanted QVLP (30 μg/strain), which was shown 
to be non-inferior to another licensed influenza vaccine. This quadrivalent influenza vaccine is a 
non-infectious, plant-derived influenza vaccine that will contain four types of purified VLP, each 
bearing trimeric, recombinant HA proteins of one of the targeted strains and is formulated to 
match the influenza virus strains as per the WHO recommendations for the 2020-2021 influenza 
season in the Northern Hemisphere. 
The other active comparator will be an approved influenza vaccine, Fluzone HD Quad. This 
quadrivalent influenza vaccine will contain four split-virion, inactivated influenza virus strains 
propagated in embryonated chicken eggs, based on the influenza strains recommended by WHO 
for the 2020-2021 influenza season. Each 0.7 mL dose of vaccine contains 60 μg of 
hemagglutinin of each of the four influenza virus strains. 
14.1.3 Preparation and Administration of Study Vaccine 
The study treatments will be prepared by unblinded staff members at the clinical site as 
described in the Investigational Product Management Manual. The prepared study treatment will 
subsequently be administered to subjects by an unblinded staff member. 
Note: The personnel responsible for treatment preparation can also perform the vaccination (if 
certified and qualified to do it) as this person would already be unblinded. The unblinded staff 
members must not be involved in the evaluation of any AEs or reactogenicity evaluations 
following vaccination. 
The products to be used for study treatment administration will be handled in a clean 
environment in an aseptic manner for preparation for injection as follows: 
x For the administration of the adjuvanted QVLP at a volume of 0.7 mL, the site will use a 
single dose vial of QVLP, a vial of AS03, and diluent (for use with half dose of AS03) that 
require mixing prior to vaccination; 
x For the administration of the unadjuvanted QVLP at a volume of 0.7 mL, the site will use a 
single dose vial of QVLP and diluent that require mixing prior to vaccination;  
x For the administration of Fluzone HD Quad at a volume of 0.7 mL, the site will prepare and 
administer the vaccine as per the manufacturer’s information. 
All study treatments will be administered on study Day 0 as an IM injection. For subjects with 
BMI < 30 kg/m2, a 23 gauge needle of at least one inch or 2.5 cm in length can be used for 
vaccination. For subjects with BMI  30 kg/m2, a needle of at least 1.5 inches or 3.5 cm in length 
must be used to ensure intramuscular delivery. According to randomization scheme, subjects will 
receive either adjuvanted or unadjuvanted QVLP or Fluzone HD Quad in the deltoid muscle of 
(preferably) the non-dominant arm. Whenever possible, the injection will be given in the 

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opposite arm from which blood samples are drawn, when applicable. 
The product administered will be recorded in study-specific documentation (refer to 
Investigational Product Management Manual) by the clinical site, which will be separate from 
the study medication record for drug preparation. After drug accountability monitoring and 
reconciliation has been completed by the site and unblinded monitor, all study treatments (used 
and unused vials) will be destroyed locally upon Medicago’s approval or returned to Medicago (or 
its designee) in accordance with instructions provided in the Investigational Product 
Management Manual. 
Further specific information relating to treatment preparation, storage, and shipment is provided 
in the Investigational Product Management Manual. 
14.1.4 Preparation, Handling, Storage, and Precautions for Use 
The study treatment (including QVLP, the adjuvant, and Fluzone HD Quad) should be stored in 
an access-restricted area between 2 ºC and 8 ºC and protected from light; the vaccine should, 
however, be at room temperature before administration (i.e. the vaccine should not be 
administered cold and should be taken out of the refrigerator at least five minutes prior to 
administration). In the event of a storage temperature deviation outside of the permitted window 
of 2 ºC to 8 ºC, the study treatment should be quarantined (at the required storage temperature) 
and Medicago (or its designee) contacted immediately. 
Note: The vaccine must NEVER be frozen, since freezing destroys activity; any vaccine that 
has been frozen must not be used. 
Note: The QVLP and the adjuvant AS03 must NEVER be vigorously shaken or vortexed. 
Note: The treatments must NOT be administered intravenously, subcutaneously, or 
intradermally. 
The Investigational Product Management Manual provides additional details on treatment 
preparation, handling and storage. 
14.2 Packaging 
Adjuvanted QVLP will be presented as a single dose vial of QVLP and a vial of the adjuvant 
AS03 and packaged in separate boxes. The active comparator, unadjuvanted QVLP, will be 
packaged in boxes containing single dose vials. The other active comparator, Fluzone HD Quad, 
will be provided as packaged by the manufacturer. 
14.3 Labeling 
The vials will have a product and study-specific label containing information that meets the 
applicable regulatory requirements. 
Blinding measures will be applied to maintain the observer-blindness of the blinded staff and to 
allow identification of the study treatment only by staff involved in the 
preparation / administration of the study vaccine / active comparators. 

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14.4 Drug Accountability 
The Investigator is responsible for ensuring that all study treatments received at the site are 
inventoried and accounted for throughout the study. The dispensing of study treatment to each 
subject must be documented on study-specific documentation. 
The study treatments or drugs must be handled in strict accordance with the Investigational 
Product Management Manual and the vial and syringe labels and will be stored in a limited 
access area or in a locked cabinet under appropriate environmental conditions. All unused study 
drugs must be available for verification by Medicago’s (or its designee’s) unblinded site monitor 
during on-site monitoring visits. The return of all unused study drugs to Medicago (or its 
designee) for destruction will be documented on study-specific documentation. When the site is 
authorized by Medicago (or its designee) to destroy study drug supplies on site, this must also be 
documented. 
The study drug should be dispensed under the supervision of the Investigator (or a qualified 
member of the investigational staff), who remains blinded as to which treatment is administered. 
The study drug will be supplied only to subjects participating in the study. Returned study drugs 
may not be relabeled or reassigned for use for other subjects. The Investigator agrees neither to 
dispense the study drug from, nor store it at, any site other than the study centers agreed upon 
with Medicago (or its designee). 
15 STUDY-SPECIFIC MATERIALS 
The Investigator will be provided with the following: 
x eCRF; 
x Forms and questionnaires for special assessments; 
x Thermometers and measurements template; 
x Study manuals. 
16 ETHICAL ASPECTS 
16.1 Study-Specific Design Considerations 
On-going medical review will be performed by Medicago (or its designee) throughout the 
duration of the study; subjects will be given any new information that may affect their decision 
to continue participation in the study. 
Blood samples will be collected from subjects for immunogenicity analysis, although not all will 
be analysed. Since blood sample collection is a minimally invasive procedure and the amount of 
blood collected will be a relatively small amount (Table 5), the benefits of obtaining this data 
outweigh the small level of risk associated with the collection of samples that may not require 
analysis. 

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16.2 Regulatory Ethics Compliance 
16.2.1 Investigator Responsibilities 
The Investigator is responsible for ensuring that the study is performed in accordance with the 
protocol, current International Conference on Harmonisation (ICH) guidelines on Good Clinical 
Practice (GCP), and applicable regulatory and country-specific requirements. 
GCP is an international ethical and scientific quality standard for designing, conducting, 
recording, and reporting studies that involve the participation of human subjects. Compliance 
with this standard provides public assurance that the rights, safety, and well-being of study 
subjects are protected, consistent with the principles that originated in the Declaration of 
Helsinki, and that the study data are reliable. 
16.2.2 Independent Ethics Committee or Institutional Review Board 
Before the start of the study, the Investigator (or Medicago, where required) will provide the 
Independent Ethics Committee (IEC)/IRB with current and complete copies of the following 
documents (as required by local regulations): 
x Final protocol and, if applicable, amendments to the protocol; 
x Sponsor-approved ICF (and any other written materials to be provided to the subjects); 
x IB (or equivalent information) and amendments/addenda; 
x If applicable, Sponsor-approved subject recruiting materials; 
x Information on compensation for study-related injuries or payments to subjects for 
participation in the study, if applicable; 
x Investigator’s curriculum vitae or equivalent information (unless not required, as 
documented by the IEC/IRB); 
x Information regarding funding, name of the sponsor, institutional affiliations, other 
potential conflicts of interest, and incentives for subjects; 
x Any other documents that the IEC/IRB requests to fulfill its obligation. 
This study will be undertaken only after the IEC/IRB has given full approval of the final 
protocol, amendments (if any, excluding the ones that are purely administrative in nature, with 
no consequences for subjects, data, or study conduct), the ICF, applicable recruiting materials, 
and subject compensation programs, and Medicago (or its designee) has received a copy of this 
approval. This approval letter must be dated and must clearly identify the IEC/IRB and the 
documents being approved. In addition, the Investigator must wait for written confirmation from 
Medicago (or its designee) that the study can be started. 
During the study, the Investigator (or Medicago [or its designee], where required) will send the 
following documents and updates to the IEC/IRB for their review and approval, where 
appropriate: 
x Protocol amendments; 

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x Revision(s) to ICF and any other written materials to be provided to subjects; 
x If applicable, new or revised subject recruiting materials approved by Medicago; 
x Revisions to compensation for study-related injuries or payment to subjects for 
participation in the study, if applicable; 
x New edition(s) of the IB and amendments/addenda; 
x Summaries of the study at intervals stipulated in guidelines of the IEC/IRB (at a minimum, 
annually); 
x Reports of AEs that are serious, unlisted/unexpected, and associated with the study drug 
(when applicable); 
x New information that may adversely affect the safety of the subjects or the conduct of the 
study; 
x Deviations from or changes to the protocol to eliminate immediate hazards to subjects; 
x Reports of deaths of subjects under the Investigator’s care; 
x Notification if a new Investigator is responsible for the study at any of the sites; 
x Development Safety Update Report and Line Listings, where applicable; 
x Any other requirements of the IEC/IRB. 
At least once a year, the IEC/IRB will be asked to review and reapprove this study. The re-
approval should be documented in writing. At the end of the study, the Investigator (or Medicago 
[or its designee], where required) will notify the IEC/IRB of study completion. 
16.2.3 Informed Consent 
Each subject who participates in the study must first give written consent according to local 
requirements after the nature of the study has been fully explained, including the risks and 
requirements of the study. The consent form must be signed before performing any study-related 
activity. The consent form that is used must have been approved by regulatory authorities, 
Medicago, and the reviewing IEC/IRB. The informed consent should be in accordance with 
principles that originated in the Declaration of Helsinki, current ICH and GCP guidelines, 
applicable regulatory requirements, and Medicago policy. During the study, subjects will be 
given any new information that may affect their decision to continue their participation in the 
study. They will be told that their consent to participate is voluntary and that it may be 
withdrawn at any time, with no reason given, and without penalty or loss of benefits to which 
they would otherwise be entitled. Only subjects who are fully able to understand the risks, 
benefits, and potential AEs of the study and who provide their consent voluntarily will be 
enrolled. 
16.2.4 Privacy of Personal Data 
The collection and processing of personal data from subjects enrolled in this study will be 
limited to those data that are necessary to support the development, registration, and future 
marketing of the investigational product. The data must be collected and processed with adequate 

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precautions to ensure confidentiality and compliance with applicable data privacy protection 
laws and regulations. Appropriate technical and organizational measures to protect the personal 
data against unauthorized disclosures or access, accidental or unlawful destruction, or accidental 
loss or alteration must be in place. Medicago (or its designee) personnel whose responsibilities 
require access to personal data agree to keep the identity of study subjects confidential. 
17 ADMINISTRATIVE REQUIREMENTS 
17.1 Protocol Amendments 
Neither the Investigator nor Medicago will modify this protocol without a formal amendment. 
All protocol amendments must be issued and approved by Medicago and signed and dated by the 
Investigator. Protocol amendments must not be implemented without prior IEC/IRB approval or 
when the relevant competent authority has raised any grounds for non-acceptance, except when 
necessary, in order to eliminate an immediate hazard to the subjects, in which case the 
amendment must be promptly submitted to the IEC/IRB and relevant competent authority. 
Documentation of amendment approval by the Investigator and IEC/IRB must be provided to 
Medicago or its designee. 
Note that administrative changes may be implemented without prior IRB approval; however, 
the Investigator or Medicago, as applicable, must notify the IRB of any administrative change 
and ensure that IRB acknowledges receipt of the administrative changes. 
The Investigator is responsible for notifying the IRB of all protocol amendments and ensuring 
that the IRB has approved any amendments when local IRBs are used. When a central IRB is 
used, Medicago or its designee will inform the IRB on behalf of the sites. 
During the course of the study, in situations where a departure from the protocol is unavoidable, 
the Investigator or other physician in attendance will contact the appropriate Medicago 
representative or its designee (see Contact Information pages provided separately). Except in 
emergency situations, this contact should be made before implementing any departure from the 
protocol. In all cases, contact with Medicago or its designee must be made as soon as possible to 
discuss the situation and to agree on an appropriate course of action. The data recorded in the 
eCRF and source documents will reflect any departure from the protocol, and the source 
documents will describe this departure and the circumstances that made a deviation necessary. 
17.2 Regulatory Documentation 
17.2.1 Regulatory Approval/Notification 
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities 
in each respective country, as applicable. A study may not be initiated in the respective country 
until all local regulatory requirements are met. 
17.3 Source Documentation 
At a minimum, source documentation must be available for the following information: 

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x Subject identification, eligibility, and study identification; 
x ICF discussion and date of informed consent; 
x Dates of visits; 
x Results of safety and study procedures as required by the protocol; 
x Record of all reactions, AEs, and associated follow-ups; 
x Concomitant medication; 
x Drug receipt, dispensing, and return records; 
x Study drug preparation and administration information; 
x Date of study completion and reason for early discontinuation of study drug or withdrawal 
from the study, if applicable. 
It is recommended that the author of an entry in the source documents be identifiable. 
At a minimum, the type and level of detail of source data available for a study subject should be 
consistent with that commonly recorded at the site as a basis for standard medical care. If 
Investigator judgement was used in the determination of eligibility, an explanation for inclusion 
of the subject in the study must be provided in the source documents. Specific details required as 
source data for the study will be reviewed with the Investigator before the study and will be 
described in the monitoring guidelines (or other equivalent document). 
17.3.1 Diary and Memory Aid 
Subjects will be provided with a diary (manual or electronic) in which to record AEs and other 
safety information. Subject diaries are considered source documents; the manual diary will be 
returned by the subject to the site at the Day 28 visit and kept with each subject’s study chart. In 
the event the manual diary is lost by the subject, information collected by the coordinator or 
designee and information recalled by the subject will serve as the source data for this subject. 
The recalled information will be captured in the source documents. The electronic diary will 
capture information directly in the electronic data capture system. 
Corrections to data entered by the subject in the diary should only be performed by the subject 
him/herself, when possible. Clarifications can be made in the comment section of the manual 
diary by the study personnel if the subject is not present onsite to make the correction 
him/herself. 
Subjects will be provided with memory aids (manual or electronic) to record information on 
unsolicited AEs, SAEs, AESIs, MAAEs, NOCDs, AEs leading to withdrawal, and reportable 
concomitant medications from the Day 0 to Day 28, Day 29 to Day 182, and Day 183 to the end 
of the study (Day 365). These memory aids will be collected by the site and are intended to be 
used by the subject to help them in reporting this information to site staff during phone contacts 
and clinical site visits. The electronic memory aids will capture information directly in the 
electronic data capture system. 

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17.4 Case Report Form Completion 
An eCRF will be provided for each subject who is randomized and receives a dose of study 
vaccine. Screening failures will also be entered in an eCRF; data entered should include date of 
birth and reason for screening failure. 
Data must be entered into the eCRFs in English. The Investigator must verify that all data entries 
in the eCRFs are accurate and correct. All eCRF entries, corrections, and alterations must be 
made by the Investigator or other authorized study-site personnel. 
Please refer to the eCRF completion guidelines for details of data entry requirements. 
17.5 Quality Control (Study Monitoring) 
In accordance with applicable regulations, GCP, and Medicago (or its designee) procedures, the 
site will be contacted prior to the study start to review the protocol and study requirements with 
the clinical study staff. Medicago (or its designee) will review their responsibilities to satisfy 
regulatory, ethical, and company (Medicago) requirements. 
The Investigator or institution, if applicable, will authorize and provide direct access to all 
relevant documents to allow review of the appropriate conduct of the study by Medicago’s (or its 
designee’s) monitor. The Investigator(s) must allocate their time and the time of their staff to the 
monitors, discuss any findings or issues, and take appropriate actions to maintain the quality and 
integrity of the study data and conduct. 
Protocol deviations will be reviewed by Medicago (or its designee) to identify any non-
compliances likely to have a significant effect on the safety and rights of a subject or the 
reliability and robustness of the data generated. These deviations will be included in the clinical 
study report. 
17.6 Quality Assurance 
To ensure compliance with GCP and all other applicable regulatory requirements, Medicago (or 
its designee) may conduct quality assurance assessments and/or an audit of the site. Regulatory 
agencies may conduct regulatory inspections at any time during or after completion of the study. 
If an audit or an inspection is conducted, the Investigator and/or institution (if applicable) must 
agree to grant auditors or inspectors direct access to all relevant documents and to allocate their 
time and the time of their staff to discuss the conduct of the study and any findings or issues, and 
to implement corrective and/or preventative actions to address any findings or issues identified. 
17.7 Record Retention 
Following closure of the study, the Investigator must maintain all site study records in a safe and 
secure location. The records must be easily accessible when needed (e.g. for a Medicago [or its 
designee] audit or regulatory inspection) and must be available for review in conjunction with 
assessment of the facility, supporting systems, and relevant site staff. 
When permitted by local laws and regulations or institutional policy, some or all of the records 

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may be maintained in a format other than a hard copy (e.g. scanned electronic). The Investigator 
must ensure that all reproductions are legible and are a true and accurate copy of the original. 
The Investigator must follow the time period for retaining the site records in order to comply 
with all applicable regulatory requirements. The minimum retention time will meet the strictest 
standard applicable to a particular site, as dictated by local laws and regulations, Medicago (or its 
designee) standard operating procedures (SOPs), and/or institutional requirements. The 
Investigator must contact Medicago (or its designee) prior to the disposal of any study 
documents at the end of the retention period. 
If the responsible Investigator retires, relocates, or, for any other reason, withdraws from the 
responsibility of keeping the study records, custody must be transferred to another qualified 
person who will accept the responsibility and is approved by Medicago. Medicago (or its 
designee) must be notified in writing of the name and address of the new custodian. Under no 
circumstance shall the Investigator relocate or dispose of any study documents without having 
obtained prior written approval from Medicago (or its designee). 
If it becomes necessary for Medicago or the appropriate regulatory authority to review any 
documentation relating to this study, the Investigator (or new custodian) must permit access to 
such reports in a timely manner. 
17.8 Study Completion/Termination 
17.8.1 Study Completion 
The study will be considered to be completed when the last contact with the last subject 
participating in the study has occurred. The final data from the investigational site will be sent to 
Medicago (or designee) after completion of the final subject visit at that site. Investigational sites 
will be closed after study completion. An investigational site is considered closed when all 
required documents and study supplies have been collected, all data have been entered, 
monitored, locked, and signed and a site closure visit has been performed. 
17.8.2 Study Termination 
Medicago (or its designee) reserves the right to close the investigational site or terminate the 
study at any time for any reason at the sole discretion of Medicago. Investigational sites will be 
closed after study termination once Medicago (or its designee) has completed all study related 
tasks. Reasons for the early closure of an investigational site by Medicago (or its designee) or the 
Investigator may include, but are not limited to: 
x Failure of the Investigator to comply with the protocol, Medicago’s (or its designee’s) 
procedures, or GCP guidelines; 
x Inadequate recruitment of subjects by the Investigator; 
x Discontinuation of further drug development. 
The Investigator may initiate site closure at any time, provided there is reasonable cause and 

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sufficient notice is given in advance of the intended closure. 
Site closure following an Investigator request can only be performed when all active study 
subjects have completed the study period, Medicago (or its designee) has collected all required 
documents and study supplies, and all data have been entered, monitored and locked. 
17.9 Registration of Clinical Studies and Disclosure of Results 
Study information from this study will be posted on publicly available clinical trial registries in 
countries where applicable and will include information required by law. In addition, the results 
summary will be posted to the same clinical trial registries, to the extent specified by law, and 
will include information required by regulatory authorities. 
17.10  Publication Policy 
The data derived from this study are the property of Medicago and cannot be published without 
prior authorization from Medicago. Any publication activities (i.e. preparation and submission of 
abstracts and manuscripts) will be at the discretion of Medicago.  
Any proposed publication regarding this study, not prepared by Medicago personnel, must be 
provided to Medicago for comments and review at least 45 days prior to its intended publication. 
The proposed publication shall not include any confidential information or protected information 
to preserve Intellectual Property rights; any such information must be removed from the 
proposed publication.  
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19.4 Appendix 4 – Seven-Day Safety Summary (Sample) 
1. Study Description
a.
Brief statement of the purpose of trial.
2. Recruitment Status
a.
Listings of enrollment status by site – (# screened, # enrolled, # vaccinated, #
withdrawn or dropped out).
3. Safety Data Listings – present data by subject
a.
Severity (including hospitalization), duration, and relationship of any AEs;
b. Vital signs abnormalities;
c.
Safety lab abnormalities;
d. Concomitant medication;
e.
Physical examination abnormalities.
4. Safety Data – present data by treatment groups
a.
Safety data overview (number of subjects experiencing AEs, SAEs, solicited AEs,
unsolicited AEs, related AEs, lab abnormalities, vital signs abnormalities, physical
examination abnormalities);
b. Present solicited AEs and solicited Grade 3-4 AEs;
c.
Present related-solicited AEs and related-solicited Grade 3-4 AEs;
d. Present unsolicited non-serious AEs and unsolicited non-serious Grade 3-4 AEs;
e.
Present related-unsolicited non-serious AEs and related-unsolicited none-serious
Grade 3-4 AEs;
f.
Present SAEs and related-SAEs by SOC/PT.