A Randomized, Double-blind, Placebo-controlled, First-in-human Phase 1/2a Study to Evaluate Safety, Reactogenicity and Immunogenicity of a Universal Influenza (Uniflu) Vaccine With INFLUENZA G1 mHA in Healthy Adults
Phase: PHASE1
Conditions: Influenza Prevention
Sponsor: Janssen Vaccines & Prevention B.V.

CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
1
Status: Approved,  Date: 02 March 2023
Janssen Vaccines & Prevention B.V.*
Clinical Protocol
A Randomized, Double-blind, Placebo-controlled, First-in-human Phase 1/2a Study to
Evaluate Safety, Reactogenicity and Immunogenicity of a Universal Influenza (Uniflu)
Vaccine with INFLUENZA G1 mHA in Healthy Adults
Protocol VAC21148FLZ1001; Phase 1/2a
Version: Amendment 2
VAC21148 Uniflu Vaccine
* Janssen Vaccines & Prevention B.V. is a Janssen pharmaceutical company of Johnson & Johnson and is
hereafter referred to as the sponsor of the study. The sponsor is identified on the Contact Information page
that accompanies the protocol.
IND NUMBER: 28494
Status: 
Approved
Date: 
02 March 2023
Prepared by: Janssen Research & Development, LLC
EDMS number: 
EDMS-ERI-191066971, 3.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory
requirements.
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that the Company
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or
otherwise.
NCT05901636

VAC21148 Uniflu Vaccine 
Clinical Protocol VAC21148FLZ1001 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
2
Status: Approved,  Date: 02 March 2023
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document 
Date
Amendment 2 
02-Mar-2023
Amendment 1 
23-May-2022
Original Protocol 
15-Jan-2020
Amendment 2 (02 March 2023)
Overall Rationale for the Amendment: To remove Ad26.FLU.003 from the VAC21148FLZ1001 study
due to changes in the sponsor’s vaccine development strategies.
The changes made to the clinical protocol VAC21148FLZ1001 as part of Protocol Amendment 2 are listed
below, including the rationale of each change and a list of all applicable sections. Changes made in previous
protocol amendments are listed in Section 10.8, Appendix 8: Protocol Amendment History.
Section Number 
and Name
Description of Change 
Brief Rationale
Protocol Title; 1.1.
Synopsis; 2. Introduction; 3.
Objectives and Endpoints;
4. Study Design; 5.2.
Exclusion Criteria; 6.1.
Study Vaccine(s)
Administered; 6.8. Study
Pausing Rules; 7.1.
Discontinuation of Study
Vaccine; 8.3. Adverse
Events, Serious Adverse
Events and Other Safety
Reporting; 9.2. Sample Size
Determination; 10.3.
Regulatory, Ethical, and
Study Oversight
Considerations; 10.4.
Adverse Events: Definitions
and Procedures for
Recording, Evaluating,
Follow-up and Recording;
10.6. Clinical Laboratory
Tests; 10.7. Thrombotic
Events to be Reported as
AESIs
Removed Ad26.FLU.003, its related
background information, and its related
objectives/endpoints and exclusion criteria.
Removed adverse event of special interest for
thrombosis with thrombocytopenia syndrome.
Removed due to changes in
sponsor’s vaccine development
strategies.
Removed due to removal of
Ad26.FLU.003.
1.1. Synopsis; 4.1. Overall
Design; 4.2. Scientific
Rationale for Study Design;
6.3. Measures to Minimize
Bias: Randomization and
Blinding; 7.4. Staggered
Vaccination; 9.2. Sample
Size Determination; Figure
2. Participant Enrollment
Adjusted cohorts and groups, as well as the
number of participants in each group.
Adjusted Cohort 1: removed the
Ad26.FLU.003 group, and increased the
number of participants in the remaining 3
groups to a total of 60 participants (25
participants for low-dose active regimen
[Groups 1 & 2] and 10 participants for
placebo [Group 3]). Adjusted Cohort 2:
removed the Ad26.FLU.003 group, and added
Ad26.FLU.003 groups were
removed based on changes in the
sponsor’s vaccine development
strategies. Single-dose groups
were added to evaluate longevity
of immune responses elicited by
single-dose of INFLUENZA G1
mHA, with or without Al(OH)3
adjuvant. The number of
participants for high-dose groups

VAC21148 Uniflu Vaccine 
Clinical Protocol VAC21148FLZ1001 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
3
Status: Approved,  Date: 02 March 2023
Section Number 
and Name
Description of Change 
Brief Rationale
and First Dose Safety 
Strategy  
2 single-dose groups (25 participants for high- 
dose active regimen [Groups 4-7] and 10 
participants for placebo [Group 8]). Cohort 3 
was removed. The total number of 
participants for the study remains as 170. 
Cohort 1 was no longer called a safety cohort, 
and Cohort 2 was no longer called a regimen 
selection cohort. 
Updated that 1 participant from each group in 
Cohort 2 including 1 placebo will be enrolled 
in the sentinel subset, and 2 participants from 
each group in Cohort 2 including 2 placebo 
will be enrolled in the safety ramp-up subset.
Updated randomization ratios for Cohort 1 
and 2. 
remained 25 in Cohort 2 in the
amendment #2, same as the
number of participants in high-
dose groups combined from
Cohort 2 & 3 in the amendment
#1. The number of participants
for low-dose groups was
increased from 15 to 25, to match
the number for high-dose groups.
The sample size calculation is
detailed in Section 9.2, Sample
Size Determination in the
amendment #2.
Updated because 2 single-dose
groups are added in Cohort 2 at
the same dose level of2-dose
groups.
Updated to reflect the revisions
to cohorts and participant
numbers.
Protocol Title page 
Replaced EudraCT number with IND number 
Replaced due to the planned
study conduct in the United
States (not Europe).
1.1. Synopsis; 4.1. Overall 
Design 
Removed that the maximum number 
participants to be vaccinated on the same day 
should not exceed 26. 
Removed based on re-assessment
of safety risk after removal of
Ad26.FLU.003.
1.1. Synopsis Objectives 
and Endpoints; 1.2. 
Schema; 1.3.1. Schedule of 
Activities –Assessments
for all Participants; 3.
Objectives and Endpoints;
4.1. Overall Design; 8
Study Assessment and
Procedures
Changed Visit 6 from Day 148 (3 months post 
second vaccination) to Day 238 (6 months 
poste second vaccination). 
Changed to better assess
durability of immune responses
elicited by the study vaccine.
1.1. Synopsis Objectives 
and Endpoints; 1.1. 
Synopsis Immunogenicity 
Evaluations; 3. Objectives 
and Endpoints; 8.1.
Immunogenicity 
Assessments 
Removed the term “humoral and cellular” 
from exploratory objectives for 
immunogenicity. 
Removed the term “stem” from the 
exploratory endpoint below for 
immunogenicity: 
HA stem- or epitope-specificity as measured 
by ELISAs using HA stem protein, or 
competition ELISAs using broadly
neutralizing antibodies (bnAbs) or HA stem
protein.
Added antibody-dependent cellular 
phagocytosis assay for functional 
Removed to avoid confusion on
humoral and cellular immune
responses for assays included in
the exploratory endpoints.
Removed to allow additional
type of hemagglutinin (HA)
protein to be used in a
competition enzyme-linked
immunosorbent assay (ELISA).
Added to allow additional assays
for functional characterization.

VAC21148 Uniflu Vaccine 
Clinical Protocol VAC21148FLZ1001 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
4
Status: Approved,  Date: 02 March 2023
Section Number 
and Name
Description of Change 
Brief Rationale
characterization of antibody response as an
exploratory endpoint for immunogenicity.
Clarified that sequencing for T cell receptor 
or B cell receptor repertoire analysis may be 
included in vaccine-induced changes in gene
expression profiles by ribonucleic acid (RNA)
sequencing or other transcriptional profiling
methods as an exploratory endpoint for
immunogenicity.
Added an exploratory objective to evaluate 
the immune responses in participants with 
confirmed influenza infection, using assays 
included for secondary and exploratory 
immunogenicity endpoints.
Clarified the expectation for
assessment on gene expression.
Added to allow assessment of
immune responses in participants
with confirmed influenza
infection.
1.1. Synopsis 
Immunogenicity 
Evaluations; 8.1.
Immunogenicity
Assessments
Added hemagglutination inhibition assays in 
the table for immunogenicity assays. 
Added to reflect exploratory
endpoints.
1.1. Synopsis ILI 
Procedures; 8.1.1. ILI 
Procedures 
Added that the blood samples collected for 
influenza virus exposure confirmation may 
additionally be used to evaluate immune 
responses during the ILI.
Added for the newly added
Virology exploratory endpoint in
the amendment #2.
1.1. Synopsis Planned 
Analyses; 9.5. Planned 
Analyses 
Added immunogenicity data on quantification 
of antibody binding to HA stem protein in the 
primary analysis. 
Updated that only sponsor and external 
partnerships personnel who are involved in
the data analysis and decision making will be
unblinded at the time of the primary analysis.
Updated the additional analysis to occur after 
6 months post-Dose-2 visit or discontinued 
earlier. 
Updated that the additional analyses will 
include additional safety data up to the
6 months post-Dose 2 visit and
immunogenicity data required per the
sponsor’s assessment.
Added based on the sponsor’s
assessment on data required for
decision making.
Updated to clarify expectation.
Updated because Visit 6 was
changed from Day 148 (3 months
post second vaccination) to Day
238 (6 months poste second
vaccination).
Updated to clarify expectation.
1.1. Synopsis; 1.3.1. 
Schedule of Activities – 
Assessments for all 
Participants; 2.1. Study 
Rationale; 3. Objectives and 
Endpoints; 4.1. Overall 
Design; 6.3. Measures to 
Minimize Vias: 
Randomization and 
Blinding; 8. Study 
Sample collection, assays and exploratory 
endpoints for peripheral blood mononuclear 
cells (PBMCs) in the in-depth 
immunogenicity (IDI) subset were removed. 
PBMCs were included in the
previous protocol amendment #1
to evaluate cellular responses
elicited by study vaccines as
exploratory endpoints, in order to
facilitate decision making on
regimen selection. With removal
of Ad26.FLU.003, the sponsor
has decided not to include these
exploratory endpoints in this

VAC21148 Uniflu Vaccine 
Clinical Protocol VAC21148FLZ1001 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
5
Status: Approved,  Date: 02 March 2023
Section Number 
and Name
Description of Change 
Brief Rationale
Assessment and Procedures; 
9.3. Population for 
Analyses; 9.4.3. Secondary 
Endpoint (s)
first-in-human study and will
consider to include in future
studies.
1.1. Synopsis; 1.3.1. 
Schedule of Activities – 
Assessments for all 
Participants; 3. Objectives
and Endpoints; 8.1. 
Immunogenicity 
Assessments 
Added PAX gene sample collection. 
Added nasosorption sample collection and an 
exploratory endpoint on nasal antibody 
response. 
Added for the exploratory
endpoint on vaccine-induced
changes in gene expression.
Added to explore nasal antibody
response induced by the study
vaccine.
1.1. Synopsis Study 
Vaccine; 6.1. Study 
Vaccine(s) Administered 
Updated that alternative location for study 
vaccination is only allowed for second dose in
case both deltoids cannot be used due to a
medical or other contraindication.
Updated to clarify expectation.
1.1. Synopsis Population for 
Analyses; 9.3. Population 
for Analyses 
Updated per-protocol immunogenicity 
population to exclude samples taken on or
after the date when a participant experiences a
major protocol deviation expected to impact
the immunogenicity outcomes.
Updated to clarify expectation.
1.3.1. Schedule of Activities 
–Assessments for all 
Participants 
Adjusted visit window for Day 8 and Day 64 
visits from ± 2 days to + 2 days. 
Removed coagulation tests from all 
timepoints and hematology tests from Day 28 
and Day 85 visits. 
Added participant wallet card distribution at 
screening visit. 
Added insulated cooler bag training and 
distribution along with nasal swab kit training
and distribution
Updated footnote b to include a phone call 3 
to 5 days after Day 1 and Day 57 visits. 
Updated footnote c to clarify the visit window 
calculation should be based on the last 
vaccination visit. 
Updated footnote i to clarify that additional 
blood may be collected for participants with
influenza-like illness.
Updated footnote g for re-assessment of 
inclusion and exclusion criteria prior to study 
vaccination. 
Adjusted to ensure participants’
diaries are completed up to Day 8
after study vaccination at Day 8
and Day 64 visits for
investigators to review.
Removed based on re-assessment
ofsafety risk after removal of
Ad26.FLU.003.
Added to ensure participant
wallet card distribution.
Added to clarify expectation.
Updated to ensure that
participants are completing
diaries without issues.
Updated to ensure that the safety
follow-up and sample collection
are completed on time in
respective to the last vaccination.
Updated to clarify expectation.
Updated based on changes made
in Section 5.1. Inclusion Criteria
and 5.2. Exclusion Criteria.

VAC21148 Uniflu Vaccine 
Clinical Protocol VAC21148FLZ1001 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
6
Status: Approved,  Date: 02 March 2023
Section Number 
and Name
Description of Change 
Brief Rationale
Added footnote o for diary review with 
participants.
Added footnote p in case the screening visit 
and Day 1 visit may occur on the same day
(Day 1).
Added to clarify expectation.
Added to clarify expectation.
1.3.1. Schedule of Activities 
–Assessments for all 
Participants; 8. Study
Assessment And Procedures
Updated blood volume. 
Updated based on changes made
on sample collection.
2.3.1 Risks Related to Study 
Vaccination  
Added risks from Nasal Swab Sampling. 
Added as nasal swab sampling is
a required study procedure in
Section 1.3.2 Schedule of
Activities –Assessments for
Participants With Influenza-like
Illness (ILI).
2.3.3 Benefit-Risk 
Assessment Related to 
Study Vaccination 
Clarified that any serious clinically significant 
abnormalities (including those serious events 
persisting at the end of the study/early 
withdrawal) will be followed by the
investigator until resolution or until a
clinically stable endpoint is reached.
Clarified expectation for serious
clinically significant
abnormalities.
4.1. Overall Design  
Added that additional temperature 
measurements may be taken if a participant
does not feel well.
Added to clarify expectation.
4.2.1 Study-Specific Ethical 
Design Considerations 
Removed reference to Belgian Red Cross 
guidelines for blood volume collected. 
The study will be conducted in
the United States (US) and will
follow the US regulations and
requirements.
5.1. Inclusion Criteria 
Inclusion Criterion #1 and #5: changed he or 
she to the participant and changed women to 
female participants.
Inclusion Criterion #2: changed prohibitions 
and restrictions to lifestyle restrictions. 
Changed based on FDA feedback
to remove gender terminology.
Changed for consistency with
Section 5.3. Lifestyle
Considerations.
5.2. Exclusion Criteria 
Exclusion Criterion #2: Added Fahrenheit 
unit for temperature. 
Exclusion Criterion #4: Clarified to exclude 
participants with history of severe allergic 
reaction (eg, anaphylaxis) or other serious 
adverse reactions to vaccines or vaccine 
excipients (specifically the excipients of the 
study vaccine[s]).
Exclusion Criterion #5: Added treatments to 
clinical conditions that are expected to have
an impact on the immune response elicited by
the study vaccine.
Exclusion Criterion #7: Added chronic for 
eczema and atopic dermatitis.
Added in consideration of the
study conduct in the US.
Clarified to include other serious
adverse reactions to vaccines or
vaccine excipients (specifically
the excipients of the study
vaccine[s]).
Added to clarify expectation.
Added to clarify expectation.

VAC21148 Uniflu Vaccine 
Clinical Protocol VAC21148FLZ1001 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
7
Status: Approved,  Date: 02 March 2023
Section Number 
and Name
Description of Change 
Brief Rationale
Exclusion Criteria #8: Added 
immunoglobulins (including monoclonal
antibodies) expected to impact the vaccine-
induced immune response.
Exclusion Criteria #10: Added to exclude 
participants who received an investigational
biological product within 3 months or 5 half-
lives, whichever is longer, before the planned
study intervention, and added a note to clarify
a couple of exceptions.
Exclusion Criterion #14: Added examples for 
major surgeries and updated to exclude
participants who has major surgery planned
within 3 months after any dose of study
vaccination
Exclusion Criterion #24: removed exclusion 
criterion for participants who has taken any 
disallowed therapies as noted in Section 6.5 
Concomitant Therapy. 
Added to clarify expectation.
Added to clarify expectation.
Updated to clarify expectation.
Removed as the updated Section
6.5 Concomitant Therapy now
references Section 5.2, Exclusion
Criteria for disallowed therapies
and all disallowed therapies have
been covered in other exclusion
criteria.
6.3. Measures to Minimize 
Vias: Randomization and 
Blinding 
Added language for unblinding of selected 
sponsor personnel in rare circumstances. 
Added to clarify expectation on
unblinding for rare
circumstances.
6.5. Concomitant Therapy  
Added that any vaccination within 6 months 
before screening must be recorded at
screening.
Added that any vaccination must be recorded 
until the end of the study.
Removed details on the disallowed therapies 
and referenced Section 5.2, Exclusion Criteria 
instead.
Added that any use of disallowed medication 
is to be recorded in the CRF.
Added to clarify expectation.
Added to clarify expectation.
Updated for simplification of the
protocol.
Added to clarify expectation.
7.1. Discontinuation of 
Study Vaccine 
Added severe hypersensitivity reaction 
following study vaccination, not attributable
to causes other than vaccination, as a criterion
to discontinue study vaccine.
Added withdrawal of consent to receive 
further vaccination as a criterion to
discontinue study vaccine.
Added to clarify expectation.
Added to clarify expectation
7.1.1 Criteria for 
Temporarily Delaying 
Study Vaccine
Administration 
Added Fahrenheit unit for temperature 
Added an illness which in the judgement of 
the investigator may interfere with
reactogenicity/Day 1-8 safety assessments
Added in consideration of the
study conduct in the US.
Added to clarify expectation.

VAC21148 Uniflu Vaccine 
Clinical Protocol VAC21148FLZ1001 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
8
Status: Approved,  Date: 02 March 2023
Section Number 
and Name
Description of Change 
Brief Rationale
after each vaccination, as a criterion for
temporarily delay study vaccination.
Added that vaccination may be delayed for 
reasons other than acute illness at
investigator’s discretion. Vaccination must be
completed within the specified window and
upon approval of the sponsor. A check of
eligibility criteria may be repeated as
necessary.
Added to clarify expectation.
7.2. Participant 
Discontinuation/Withdrawal 
From the Study  
Added the following reasons for possible 
participant withdrawal: 
 
Decision by the sponsor or the
investigator to stop or cancel the study
 
Decision by local regulatory authorities
or IRB/IEC to stop or cancel the study
Added in consideration of
regulatory requirements.
8. Study Assessment and 
Procedures; 8.1.1. ILI 
Procedures 
Added insulated cooler bag as study-specific 
materials to be provided to sites for
participants to transfer nasal swab samples
collected at home to sites at defined
temperature.
Added to clarify expectation.
8.1. Immunogenicity 
Assessments 
Added that samples collected for 
immunogenicity analyses may additionally be 
used to evaluate serology (HAI assays). 
Added to allow assessment of
influenza infection by HAI
assays if needed for participants
who don’t have symptoms of
influenza-like illness reported
during the study.
8.2.1. Physical 
Examinations 
Added that weight will be measured lightly 
clothed and without footwear, and height will
be measured without footwear.
Added that any clinically relevant 
abnormalities or changes in severity observed
during the review of body systems should be
documented in the eCRF as an AE or SAE if
it meets the criteria for an AE or SAE
according to the protocol reporting
requirements, and any abnormalities or
changes in severity that occurred after signing
of the ICF until immediately before
vaccination would be recorded ifdue to
participation in the study.
Added to clarify expectation.
Added to clarify expectation.
8.2.2. Vital Signs 
Added that vital signs will be examined as 
specified in Section 1.3, Schedule of
Activities.
Added to clarity expectation.
8.3.1. Time Period and 
Frequency for Collecting 
Adverse Event and Serious 
Adverse Event Information; 
8.3.5. Pregnancy; 10.4. 
Appendix 4: Adverse
Events: Definitions and
Procedures for Recording,
Updated that AEs of Grade 3 or above, SAEs, 
pregnancy events and product quality
complaints must be reported to the sponsor by
study-site personnel immediately, but no later
than 24 hours of their knowledge of the event.
Updated to clarify expectation.

VAC21148 Uniflu Vaccine 
Clinical Protocol VAC21148FLZ1001 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
9
Status: Approved,  Date: 02 March 2023
Section Number 
and Name
Description of Change 
Brief Rationale
Evaluating, Follow-up, and
Reporting
8.3.2 Method of Detecting 
Adverse Events and Serious 
Adverse Events 
Added that the study staff will verbatim 
transcribe the information provided by the
participant into the relevant sections of the
CRF. Review of diary entries with
participants and grading of symptoms must be
done by a qualified and delegated study staff
member under the oversight of the
investigator or a delegated physician.
Added to clarify expectation.
10.1. Appendix 1: 
Abbreviations 
Updated abbreviations. 
Updated based on changes in the
amendment #2.
10.2. Appendix 2: 
Contraceptive Guidance and 
Collection of Pregnancy  
Information
Updated definition of permanently sterile for 
female participant not of childbearing 
potential.
Updated per the sponsor
assessment.
10.3. Appendix 3: 
Regulatory, Ethical and 
Study Oversight 
Considerations Long-term 
Retention of Samples for 
Additional Future Research
Added that no additional research on study 
participants, study samples, or data derived
from the study will be conducted by the
institution(s) or by a third party, without the
prior written consent of the sponsor.
Added that sample will be used to understand 
influenza or other respiratory diseases, and
the study intervention platform.
Removed DNA testing. 
Added to clarify expectation.
Added to clarify expectation.
Removed since samples are not
collected for DNA testing.
10.6. Appendix 6: Clinical 
Laboratory Tests 
Removed coagulation test and tests related to 
adverse event of special interest. 
Removed based on change in the
amendment #2.
10.8. Appendix 8: Protocol 
Amendment History  
Updated to include summary of changes table 
for amendment #1. 
Updated to reflect amendment
history.
11. References 
Removed some references. 
Removed references that are no
longer cited based on changes in
the amendment #2.
Throughout the protocol 
Reference to gender (woman, etc.) was 
replaced by sex (male and female). 
Updated based on FDA feedback
to remove gender terminology.
Throughout the protocol 
Minor language updates were made for 
consistency and clarification. 
Minor language updates made
throughout the protocol to clarify
and be consistent with the
changes noted in the sections
listed above.
Throughout the protocol 
Minor grammatical, formatting, or spelling 
changes were made.
Minor errors were noted

VAC21148 Uniflu Vaccine 
Clinical Protocol VAC21148FLZ1001 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
10
Status: Approved,  Date: 02 March 2023
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................. 10
LIST OF IN-TEXT TABLES AND FIGURES.............................................................................................. 12
1. 
PROTOCOL SUMMARY................................................................................................................... 13
1.1. 
Synopsis......................................................................................................................................... 13
1.2. 
Schema.......................................................................................................................................... 23
1.3. 
Schedule of Activities (SoA)........................................................................................................... 24
1.3.1. 
Schedule of Activities –Assessments for all Participants .......................................................... 24
1.3.2. 
Schedule of Activities –Assessments for Participants With Influenza-like Illness (ILI).............. 27
2. 
INTRODUCTION................................................................................................................................ 28
2.1. 
Study Rationale.............................................................................................................................. 28
2.2. 
Background .................................................................................................................................... 30
2.2.1. 
Nonclinical Studies ..................................................................................................................... 30
2.2.2. 
Clinical Studies ........................................................................................................................... 30
2.3. 
Benefit-Risk Assessment............................................................................................................... 31
2.3.1 
Risks Related to Study Vaccination............................................................................................ 31
2.3.2 
Benefits Related to Study Vaccination ....................................................................................... 33
2.3.3 
Benefit-Risk Assessment Related to Study Vaccination ............................................................ 33
3. 
OBJECTIVES AND ENDPOINTS ..................................................................................................... 35
4. 
STUDY DESIGN ................................................................................................................................ 36
4.1. 
Overall Design................................................................................................................................ 36
4.2. 
Scientific Rationale for Study Design............................................................................................. 41
4.2.1. 
Study-Specific Ethical Design Considerations ........................................................................... 42
4.3. 
Justification for Dose...................................................................................................................... 42
4.4. 
End of Study Definition................................................................................................................... 43
5. 
STUDY POPULATION ...................................................................................................................... 43
5.1. 
Inclusion Criteria............................................................................................................................ 43
5.2. 
Exclusion Criteria........................................................................................................................... 45
5.3. 
Lifestyle Considerations................................................................................................................. 48
5.4. 
Screen Failures.............................................................................................................................. 48
6. 
STUDY VACCINE.............................................................................................................................. 49
6.1. 
Study Vaccine(s) Administered...................................................................................................... 49
6.2. 
Preparation/Handling/Storage/Accountability ................................................................................ 50
6.3. 
Measures to Minimize Bias: Randomization and Blinding............................................................. 51
6.4. 
Study Vaccine Compliance ............................................................................................................ 53
6.5. 
Concomitant Therapy..................................................................................................................... 53
6.6. 
Dose Modification........................................................................................................................... 54
6.7. 
Intervention After the End of the Study.......................................................................................... 54
6.8. 
Study Pausing Rules...................................................................................................................... 54
7. 
DISCONTINUATION OF STUDY VACCINE AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL............................................................................................... 55
7.1. 
Discontinuation of Study Vaccine .................................................................................................. 55
7.1.1. 
Criteria for Temporarily Delaying Study Vaccine Administration................................................ 56
7.2. 
Participant Discontinuation/Withdrawal From the Study................................................................ 57
7.2.1. 
Withdrawal From the Use of Research Samples ....................................................................... 57
7.3. 
Lost to Follow-up............................................................................................................................ 57
7.4. 
Staggered Vaccination................................................................................................................... 58

VAC21148 Uniflu Vaccine 
Clinical Protocol VAC21148FLZ1001 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
11
Status: Approved,  Date: 02 March 2023
8. 
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 58
8.1. 
Immunogenicity Assessments ....................................................................................................... 61
8.1.1. 
ILI Procedures ............................................................................................................................ 62
8.2. 
Safety Assessments....................................................................................................................... 65
8.2.1. 
Physical Examinations................................................................................................................ 65
8.2.2. 
Vital Signs................................................................................................................................... 66
8.2.3. 
Clinical Safety Laboratory Assessments .................................................................................... 66
8.2.4. 
Pregnancy Testing...................................................................................................................... 66
8.3. 
Adverse Events, Serious Adverse Events, and Other Safety Reporting ....................................... 66
8.3.1. 
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event
Information.................................................................................................................................. 67
8.3.2. 
Method of Detecting Adverse Events and Serious Adverse Events .......................................... 68
8.3.3. 
Follow-up of Adverse Events and Serious Adverse Events ....................................................... 69
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events ............................................. 69
8.3.5. 
Pregnancy................................................................................................................................... 69
8.4. 
Treatment of Overdose .................................................................................................................. 70
8.5. 
Medical Resource Utilization and Health Economics .................................................................... 70
9. 
STATISTICAL CONSIDERATIONS.................................................................................................. 70
9.1. 
Statistical Hypotheses.................................................................................................................... 70
9.2. 
Sample Size Determination ........................................................................................................... 70
9.3. 
Populations for Analyses................................................................................................................ 71
9.4. 
Statistical Analyses ........................................................................................................................ 72
9.4.1. 
General Considerations.............................................................................................................. 72
9.4.2. 
Primary Endpoint(s).................................................................................................................... 72
9.4.3. 
Secondary Endpoint(s)............................................................................................................... 73
9.4.4. 
Tertiary/Exploratory Endpoint(s)................................................................................................. 73
9.5. 
Planned Analyses .......................................................................................................................... 73
9.6. 
Data Monitoring Committee or Other Review Board ..................................................................... 74
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............................ 75
10.1. 
Appendix 1: Abbreviations ............................................................................................................. 75
10.2. 
Appendix 2: Contraceptive Guidance and Collection of Pregnancy Information........................... 77
10.3. 
Appendix 3: Regulatory, Ethical, and Study Oversight Considerations......................................... 78
REGULATORY AND ETHICAL CONSIDERATIONS .......................................................................... 78
FINANCIAL DISCLOSURE .................................................................................................................. 81
INFORMED CONSENT PROCESS ..................................................................................................... 81
DATA PROTECTION ........................................................................................................................... 82
LONG-TERM RETENTION OF SAMPLES FOR ADDITIONAL FUTURE RESEARCH...................... 83
COMMITTEE STRUCTURE................................................................................................................. 83
PUBLICATION POLICY/DISSEMINATION OF CLINICAL STUDY DATA........................................... 84
DATA QUALITY ASSURANCE ............................................................................................................ 85
CASE REPORT FORM COMPLETION ............................................................................................... 86
SOURCE DOCUMENTS ...................................................................................................................... 86
MONITORING ...................................................................................................................................... 87
ON-SITE AUDITS................................................................................................................................. 87
RECORD RETENTION ........................................................................................................................ 88
STUDY AND SITE START AND CLOSURE........................................................................................ 88
10.4. 
Appendix 4: Adverse Events: Definitions and Procedures for Recording, Evaluating,
Follow-up, and Reporting............................................................................................................... 90
ADVERSE EVENT DEFINITIONS AND CLASSIFICATIONS.............................................................. 90
ATTRIBUTION DEFINITIONS.............................................................................................................. 91
SEVERITY CRITERIA.......................................................................................................................... 91
SPECIAL REPORTING SITUATIONS ................................................................................................. 93
PROCEDURES .................................................................................................................................... 93
CONTACTING SPONSOR REGARDING SAFETY............................................................................. 95
PRODUCT QUALITY COMPLAINT HANDLING.................................................................................. 95
10.5. 
Appendix 5: Toxicity Grading Scale............................................................................................... 96

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10.6. 
Appendix 6: Clinical Laboratory Tests ......................................................................................... 101
10.7. 
Appendix 7: Study Conduct During a Pandemic.......................................................................... 102
10.8. 
Appendix 8: Protocol Amendment History................................................................................... 104
11. REFERENCES................................................................................................................................. 114
INVESTIGATOR AGREEMENT............................................................................................................... 116
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Study Design: VAC21148FLZ1001........................................................................................... 36
Table 2: 
Visit Windows............................................................................................................................ 59
Table 3: 
Summary of Immunogenicity Assays........................................................................................ 62
Table 4: 
Probability of Observing at Least One Adverse Event at a Given True
Adverse Event Rate.................................................................................................................. 71
Table 5: 
Power to Detect a Significant Difference at a Given True Ratio............................................... 71
Table 6: 
Severity Assessment: Solicited Injection Site Events - Adults/Adolescents (≥12 years
of age)....................................................................................................................................... 92
Table 7: 
Severity Assessment: Solicited Systemic Events - Adults/Adolescents (≥12 years of
age)........................................................................................................................................... 93
FIGURES
Figure 1: Schematic Overview of the Study for all Cohorts ..................................................................... 23
Figure 2: Participant Enrollment and First Dose Safety Strategy ............................................................ 38

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1. 
PROTOCOL SUMMARY
1.1. 
Synopsis
A Randomized, Double-blind, Placebo-controlled, First-in-human Phase 1/2a Study to Evaluate
Safety, Reactogenicity and Immunogenicity of a Universal Influenza (Uniflu) Vaccine with
INFLUENZA G1 mHA in Healthy Adults
A candidate vaccine covering Influenza A Group 1 that is composed of INFLUENZA G1 mHA (with or
without Al(OH)3 adjuvant) has shown promise in nonclinical animal models of influenza and will be
assessed in this study.
 
INFLUENZA G1 mHA (JNJ-67920320) is an Influenza A Group 1 (G1) hemagglutinin (HA) stem-
derived protein vaccine antigen (mini-HA) derived from H1N1 A/California/07/2009 virus strain.
This will be the first-in-human (FIH) study for the INFLUENZA G1 mHA protein; therefore, no clinical
experience is available.
OBJECTIVES AND ENDPOINTS
Objectives 
Endpoints
Safety
 
Primary objective: To evaluate safety/ reactogenicity of 
INFLUENZA G1 mHA, with or without Al(OH)3
adjuvant in participants ≥18 to ≤45years of age.
 
Primary endpoints:
 
Occurrence, severity, duration and
relationship of solicited local and
systemic adverse events (AEs) for 7
days after each vaccination.
 
Occurrence, severity, duration and
relationship of unsolicited AEs for 28
days after each vaccination.
 
Occurrence and relationship of serious
adverse events (SAEs) from first
vaccination to the end of the study.
Immunogenicity
 
Secondary objective: To evaluate the humoral immune 
responses to INFLUENZA G1 mHA, with or without 
Al(OH)3 adjuvant in participants ≥18 to ≤45 years of 
age. 
 
Secondary endpoint: The magnitude of
antibodies binding to the stem or the full-
length HA protein as measured by enzyme-
linked immunosorbent assay (ELISA).
 
Exploratory objectives: To further assess the immune 
responses elicited by INFLUENZA G1 mHA, with or 
without Al(OH)3 adjuvant in participants ≥18 to ≤45
years of age.
 
Exploratory endpoints may include, but are
not limited to assessing:
 
Vaccine-induced changes to the breadth
of the antibody response within Group 1
or beyond as measured by ELISA using
full-length HA proteins indicative of
clade or group coverage
 
HA stem- or epitope-specificity as
measured by ELISAs using HA stem
protein, or competition ELISAs using
broadly neutralizing antibodies (bnAbs)
or HA proteins
 
Functional characterization of the
antibody response as measured by
assays assessing Fc-mediated functions
(eg, Fc gamma receptor [FcγR] binding

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Objectives 
Endpoints
assays to the stem or full-length HA
protein, 
or 
antibody-dependent
cytotoxicity  
assay, 
or 
antibody-
dependent cellular phagocytosis assay),
HA conformational change assays, or
other assays
 
Vaccine-induced 
changes 
to 
the
functional breadth of the antibody
response within Group 1 or beyond as
measured by virus neutralization assays
or serum transfer into animal challenge
models
 
Molecular characterization of the
antibody response as measured by
assays assessing the epitope-specificity,
glycosylation 
status, 
or 
other
characteristics of the antibody (eg, by
systems serology arrays)
 
Vaccine-induced changes in innate
immune responses by transcript- or
cytokine profiling
 
Vaccine-induced changes in gene
expression profiles by ribonucleic acid
(RNA) 
sequencing 
or 
other
transcriptional 
profiling 
methods,
including but  not limited to sequencing
for T cell receptor or B cell receptor
repertoire analysis
 
Nasal antibody response as measured by
immunoglobulin (Ig) G or IgA ELISA
in nasal secretions
 
Exploratory objective: To evaluate longevity of immune
responses elicited by INFLUENZA G1 mHA, with or
without Al(OH)3 adjuvant in participants aged ≥18 to
≤45 years.
 
Exploratory endpoint: The magnitude and
functionality of antibodies binding to the
stem or the full-length HA protein of various
strains as measured by ELISA, virus
neutralization assays, and FcγR binding
assays on Days 238 and 365.
 
Exploratory objective: To evaluate the immune
responses in participants with confirmed influenza
infection.
 
Exploratory endpoint: During the influenza
season:
 
Immune responses by assays included
for 
secondary 
and 
exploratory
immunogenicity endpoints
Virology
 
Exploratory objective: To monitor symptoms of
influenza-like illness (ILI) via the Influenza Intensity
and Impact Questionnaire (Flu-iiQTM) as well as rapid
molecular diagnosis and characterization to evaluate
infection rate in participants aged ≥18 to ≤45 years and
in relation to immunological markers.
 
Exploratory endpoints: During the influenza
season:
 
Signs and symptoms of ILI
 
Confirmation of infection by reverse
transcriptase polymerase chain reaction
(RT-PCR) or response to influenza-like
infection by serology

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Status: Approved,  Date: 02 March 2023
First-dose Cohort 1
In Cohort 1, 60 participants aged ≥18 to ≤45 years will be enrolled in a staggered approach with safety
evaluations in place before extending enrollment in this cohort and progressing to Cohort 2. Initially, 5
sentinel participants will be enrolled and randomized; 2 participants in Groups 1 and 2 and 1 participant in
Group 3 (placebo) will receive a single intramuscular (IM) injection of either 
 INFLUENZA G1
mHA, 
 INFLUENZA G1 mHA adjuvanted with Al(OH)3 or placebo on Day 1. Sentinel participants
will be contacted by telephone 48 hours post-vaccination to collect safety information. The blinded 48-hour
post-vaccination safety data in these 5 sentinel participants will be reviewed by the principal investigator(s)
(PIs) and sponsor’s study responsible physician (SRP)/medical officer. Randomization of additional
participants will be paused until this 48-hour sentinel safety evaluation is completed.
In the absence of any clinically significant findings, upon decision by PI(s) and SRP, an additional 12
participants will be enrolled (5 additional participants in Groups 1 and 2 and 2 additional participants in
Group 3 [placebo] as safety ramp-up subset).
DRC will review blinded safety data of the initial 17 participants 7 days after the first vaccination. DRC
review will be held to review available safety data of initial participants enrolled before these participants
can receive the second vaccination. Further randomization in Cohort 1 will be paused until the DRC safety
evaluation is completed. In the absence of findings from the DRC  following the first vaccination, the
remaining 43 participants in Cohort 1 will be enrolled in a 18:18:7 ratio and randomization in Cohort 2 may
be initiated simultaneously.
First-dose Cohort 2
In Cohort 2, 110 participants aged ≥18 to ≤45 years will be enrolled in a staggered approach with safety
evaluations in place before extending enrollment in this cohort. Initially, 5 sentinel participants will be
enrolled and randomized; 1 participant in each of the 5 groups (Groups 4 to 8 [including 1 placebo]) will
receive a single IM injection of either 
 INFLUENZA G1 mHA; 
 INFLUENZA G1 mHA
adjuvanted with Al(OH)3; or placebo on Day 1. Sentinel participants will be contacted by telephone
48 hours post-vaccination to collect safety information. The blinded 48-hourpost-vaccination safety data
in these 5 sentinel participants will be reviewed by the PIs and SRP. Randomization of additional
participants will be paused until this 48-hour sentinel safety evaluation is completed.
In the absence of any clinically significant findings, upon decision by PI(s) and SRP, an additional 10
participants will be enrolled and randomized in parallel (2 additional participants in Groups 4 to 8 [including
2 placebo]) as safety ramp-up subset .
DRC will review blinded safety data of the 15 participants in Cohort 2, 7 days after the first vaccination.
DRC review will be held to review available safety data of initial participants enrolled before these
participants can receive the second vaccination. Further randomization in Cohort 2 will be paused until the
DRC safety evaluation is completed. In the absence of findings from the DRC  following the first
vaccination, the remaining 95 participants in Cohort 2 will be enrolled in a 22:22:22:22:7 ratio.
Second-dose Safety
In alignment with the first-dose safety strategy, post-second dose 48-hour (sentinel participants) and 7-day
safety assessments (participants in the sentinel subset and safety ramp-up subset) will be monitored by the
CCI
CCI
CCI
CCI

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Status: Approved,  Date: 02 March 2023
 
Formulation buffer for INFLUENZA G1 mHA (Diluent Uniflu 1): supplied in a single use vial for
dilution of INFLUENZA G1 mHA according to IPPI; 0.8 mL (extractable volume)
For each participant, every injection will be 1.0 mL in volume. Instructions on study vaccine preparation
(eg, dilution in formulation buffer) into the final dose that participants receive within each treatment group
are outlined in detail in the IPPI.
Preferably the deltoid muscle of the non-dominant upper arm is used to administer the injection. If an
injection cannot be given in either deltoid for the second dose of the vaccination due to a medical or other
contraindication (for example, tattooed upper arms rendering it difficult to assess site reactogenicity), use
alternative locations such as the hip, thigh, or buttocks (to be avoided in overweight participants). In this
case, IM injections in other locations than the upper arm for the second dose of the vaccination are not
considered protocol deviations.
An unblinded pharmacist, or other qualified staff member at the site with primary responsibility for study
vaccine preparation, who will not participate in any other study evaluation, will prepare the appropriate vial
and syringe, labeled with the participant’s identification number, and provide the blinded syringe to the
blinded vaccine administrator who will perform the injection.
IMMUNOGENICITY EVALUATIONS
Immunogenicity assessments may include, but are not limited to, the humoral immunogenicity assays (as
available and applicable) summarized in the below Table.
Blood for humoral immune responses will be drawn from all participants. Influenza immunity in study
participants will be determined on baseline (Day 1) and post-vaccination blood samples as described in
Section 1.3, Schedule of Activities. Both assay variability and pre-existing immunity will be taken into
consideration in the immunogenicity assessments. PaxGene samples will allow the performance of whole
blood transcript profiling. Nasosorption samples (using SAM) will be used for the development of mucosal
influenza-specific IgG and/or IgA ELISAs and the assessment of those responses in nasal secretion.
In addition to RT-PCR based diagnosis of influenza virus infection performed on nasal swab samples
(collected when ILI symptoms develop during the influenza season), blood samples collected at baseline,
between 2 and 4 days after symptom onset (ILI Days 3-5), and at 28 days after symptom onset (ILI Day 29)
from participants with a suspected ILI will also be assayed by serology (including but not limited to
hemagglutination inhibition (HAI) assay as available and applicable) for influenza virus exposure
confirmation. Additionally, the nasal swab samples might be used to determine the presence of other
respiratory pathogens upon the sponsor's request.
Table: 
Summary of Immunogenicity Assays
Endpoint 
Assay
Secondary endpoints
Quantification of antibody binding 
to HA stem or full-length HA
ELISA
Exploratory endpoints
Neutralization  
Virus neutralization assay
Fc-mediated functionality  
Human FcγRIIIa reporter assay
Breadth of the antibody response 
within Group 1 or beyond
ELISA using full-length HAs indicative of clade or group coverage
HA stem- or epitope-specificity  
ELISAs using HA stem protein or competition ELISAs using bnAbs or
HA proteins

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Status: Approved,  Date: 02 March 2023
Functional breadth of the antibody 
response within Group 1 or beyond 
Virus neutralization assays or serum transfer into animal challenge
models
Functional characterization of the 
antibody response 
Assays assessing Fc-mediated functions (eg, antibody-dependent
cytotoxicity assay or antibody-dependent cellular phagocytosis assay),
HA conformational change assays, or other assays
Molecular characterization of the 
antibody response 
Assays assessing the epitope-specificity, glycosylation status, or other
characteristics of the antibody (eg, systems serology arrays)
Innate immune responses 
Transcript- or cytokine profiling
Gene expression profiles 
RNA sequencing or other transcriptional profiling methods, including,
but not limited to TCR or BCR repertoire analysis
Nasal antibody response 
IgG and/or IgA ELISA in nasal secretions
Hemagglutination inhibition 
HAI assays
BCR = B cell receptor; bnAbs = broadly neutralizing antibodies; ELISA = enzyme-linked immunosorbent assay; Fc = fragment
crystallizable; HA = hemagglutinin; HAI = hemagglutination inhibition; Ig = immunoglobulin; RNA = ribonucleic acid; TCR = T
cell receptor.
ILI Procedures
For the duration of the influenza season, participants will be followed-up to identify potential cases of
influenza virus infection. During the influenza season, participants should record any signs and symptoms
of ILI (such as cough, sore throat, headache, nasal congestion, feeling feverish, body aches and pains,
fatigue, or neck pain), including measurement ofbody temperature, on a daily basis until symptoms have
resolved using a specific Flu-iiQTM questionnaire and an ILI form.
If ILI symptoms develop during the influenza season, the following should take place:
 
Participants should contact the site as soon as possible to notify the site of ILI.
 
Participants should record signs and symptoms of the ILI daily using the Flu-iiQTM questionnaire from
onset of symptoms until the day of symptom resolution, and record body temperature daily using an
ILI form provided by the sponsor until the day of symptom resolution.
 
Participants should take a nasal sample at home on the day of symptom onset or the day thereafter (ILI
Days 1-2). The sample should be stored refrigerated and brought to the site by the participant within
4 days (preferably) after collection.
 
Participants should go to their study site, ideally between 2 and 4 days after symptom onset (ILI Days
3-5), where
 
the completed Flu-iiQTM questionnaire and ILI form will be collected and reviewed by site staff;
 
the participant nasal self-swab sample (taken on ILI Days 1-2) will be collected;
 
an additional nasal swab will be taken by a qualified member of the site staff;
 
the presence of influenza virus infection will be assessed by qualified site staff by RT-PCR
diagnostics and/or rapid-PCR detection (eg, by Cepheid GeneXpert®) on the nasal swab samples
mentioned above;
 
a blood sample for seroconfirmation of influenza virus infection will be taken by a qualified
member of the site staff;
 
and vital signs, including body temperature, blood pressure, heart rate, respiratory rate and oxygen
saturation, will be measured by a qualified member of the site staff. A clinical assessment,
including a targeted physical examination, will be completed by qualified site staff, preferably by
a physician, physician assistant, nurse practitioner, or equivalent.

VAC21148 Uniflu Vaccine 
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Status: Approved,  Date: 02 March 2023
 
At ILI Day 29 (±7 days), participants will be asked to return to the site where
 
the completed Flu-iiQTM questionnaire and ILI form will be collected and reviewed by site staff;
 
a blood sample for seroconfirmation of influenza virus infection will be taken by a qualified
member of the site staff;
 
and vital signs, including body temperature, blood pressure, heart rate, respiratory rate and oxygen
saturation will be measured by a qualified member of the site staff. A clinical assessment
(including a targeted physical examination) will be performed by qualified site staff, preferably
by a physician, physician assistant, nurse practitioner, or equivalent.
 
For all medically attended ILIs, including those resulting in hospitalization, additional information on
any other diagnostics (eg, chest x-rays, spirometry, pulmonary function tests) or interventions during
the clinical course of ILI will be collected.
During the influenza season, participants will be contacted by telephone or other means of communication
approximately every 14±3 days (unless a planned visit has occurred or will occur within 14 days). These
calls will remind participants to complete the Flu-iiQTM  questionnaire and ILI form in the event of any
symptoms of ILI, and to contact the site and to take a nasal sample at the time of symptom onset. These
calls will also check for any SAEs, and associated concomitant medications since the previous visit or
telephone contact.
The presence of influenza virus will be assessed by site by RT-PCR diagnostics on the nasal swab samples,
which may include viral load and influenza subtyping. In addition, blood samples from participants with a
suspected ILI will also be assayed by serology by the sponsor (including but not limited to HAI assay as
available and applicable) for influenza virus exposure confirmation. The blood samples may additionally
be used to evaluate immune responses during the ILI.
Every effort should be made to collect data on the clinical course of ILIs including information on
hospitalization,oxygenation status,supplemental oxygen requirements and specific drug treatments, as well
as other concurrent respiratory illness present at the time of the diagnosis of the event and up to symptom
resolution.
For participants who experience symptoms suggesting ILI, RT-PCR assay of the nasal swabs taken after
symptom onset will be used to determine whether the infection was caused by influenza virus. For
participants hospitalized with symptoms of ILI, confirmation of influenza virus infection using RT-PCR
may be performed at the local (hospital) laboratory.
Any ILI and complications related to ILIs will be reported as an AE if it occurs between the time of any
vaccination through the following 28 days. An ILI and complications related to ILIs that occur outside of
this period does not require AE reporting unless ongoing at the time of subsequent vaccination. Any ILI
and complications related to ILIs fulfilling the criteria of an SAE will be reported as such during the entire
study period from the first vaccination.
SAFETY EVALUATIONS
On a daily basis, for 7 days after each vaccination, participants will be asked to record symptoms of the
following AEs via the participant diary:
 
Solicited injection site AEs: erythema (measured using the ruler supplied), swelling (measured using
the ruler supplied), and pain/tenderness.

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Status: Approved,  Date: 02 March 2023
 
Solicited systemic AEs: fatigue, headache, myalgia, nausea and fever (ie, body temperature ≥38 °C
[100.4°F]).
Oral temperature should be measured at approximately the same time each day, preferably in the evening,
using the thermometer supplied. Temperature 7 days after each vaccination may be collected earlier on the
Day 8 or Day 64 to coincide with the clinic visit.
Adverse events and special reporting situations, whether serious or non-serious, that are related to study
procedures or that are related to non-investigational sponsor products will be reported from the time a
signed and dated ICF is obtained until the end of the study/early withdrawal.
Solicited AEs, collected through a diary, will be recorded for each vaccination from the moment of
vaccination until 7 days post-vaccination.
All other unsolicited AEs and special reporting situations, whether serious or non-serious, will be collected
for each vaccination from the moment of vaccination until 28 days post-vaccination. Unsolicited AEs with
the onset date outside the timeframe defined above (>28 days after previous study vaccination), which are
ongoing on the day of the subsequent vaccination, should be recorded on the electronic case report form
(eCRF) AE page.
All SAEs and AEs leading to discontinuation from further study vaccination (regardless of the causal
relationship) are to be reported from the moment of first vaccination until completion of the participant’s
last study-related procedure, which may include contact for safety follow-up. The sponsor will evaluate any
safety information that is spontaneously reported by an investigator beyond the time frame specified in the
protocol.
STATISTICAL METHODS
Sample Size Determination
With 25 participants per active regimen arm, the observation of no vaccine reactions after the first
vaccination would be associated with a 95% confidence that the true rate is less than 11.3%. Across active
regimens (N=150), the observation of 0 vaccine reactions after the first vaccination would be associated
with a 95% confidence that the true rate is less than 2.0%.
Populations for Analyses
For purposes of analysis, the following populations are defined:
 
Full Analysis Set (FAS): The FAS  will include all participants with at least one vaccination
documented.
 
Per-protocol Immunogenicity (PPI): The PPI Set will include all randomized and vaccinated
participants for whom immunogenicity data are available excluding samples taken on or after the date
when a participant experiences a major protocol deviation expected to impact the immunogenicity
outcomes.
Primary Endpoints
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively per study
group, with special attention for SAEs, Grade 3/4 AEs, and AEs leading to discontinuation of study vaccine.
All safety analyses will be made on the FAS.

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Status: Approved,  Date: 02 March 2023
Secondary Endpoints
No formal hypothesis on immunogenicity will be tested. Descriptive statistics (geometric mean and 95%
confidence interval, or median and quartile range [Q1-Q3], as appropriate) will be calculated for continuous
immunological parameters at all time points and for changes from baseline. Graphical representations of
immunological parameters will be made as applicable. Frequency tabulations will be calculated for discrete
(qualitative) immunological parameters as applicable. The immunogenicity analyses will be performed on
the PPI set. An additional analysis might be done for the FAS.
Planned Analyses
The primary analysis will occur when all participants have completed the 28 days post-Dose 2 visit or
have discontinued earlier. These analyses will include immunogenicity data on quantification of antibody
binding to full-length HA and HA stem protein and safety data up to the 28 days post-Dose 2 visit. At the
time of the primary analysis, the study will be unblinded for sponsor and external partnerships personnel
who are involved in the data analysis and decision making. Participants and study-site personnel will remain
blinded to the study vaccine allocation until the end of the study.
An additional analysis will occur when all participants have completed the 6-month post-Dose 2 visit or
discontinued earlier. These analyses will include additional safety data up to the 6 months post-Dose 2 visit
and immunogenicity data required per the sponsor’s assessment. This analysis may allow to evaluate
persistence of immune responses.
No study modifications are planned as a result of primary or additional analyses. The exact scope of each
analysis will be defined based on the availability of immunogenicity data and findings from previous
analyses. Additional interim analyses may be performed during the study for the purpose of informing
future vaccine development-related decisions in a timely manner, or upon health authority request. If
required, these unplanned interim analyses may replace or be combined with planned analyses, depending
on the timing.
The final analysis will occur when the last participant has completed the final visit of the schedule of
assessment (Day 365±30 days) or discontinued earlier. Final analyses will allow for determination of the
durability of the immune response and analyze any additional safety and immunological data collected after
the additional analysis.

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Status: Approved,  Date: 02 March 2023
1.2. 
Schema
Figure 1: 
Schematic Overview of the Study for all Cohorts
* Participants will be enrolled in a staggered approach with safety evaluations (Day 8) in place before extending enrollment in each cohort and progressing from one
cohort to the next.
Further information on the overall design of the study can be found in Section 4.1, Overall Design.

VAC21148 Uniflu Vaccine 
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Status: Approved,  Date: 02 March 2023
l. 
Concomitant therapies will be collected from the signing of the ICF until 28 days after the first vaccination and from the second vaccination through the following 28 days, and
additionally outside of these periods when associated with an SAE.
m. Signs and symptoms of influenza infection will be recorded during the influenza season using the Flu-iiQTM questionnaire and ILI form. Participants will be notified of the
influenza season. During the influenza season, they will be contacted by telephone or other means of communication every 14±3 days (unless a prescheduled clinic visit has
occurred or will occur within 14 days). Calls will remind participants to complete the Flu-iiQTM questionnaire and ILI form in the event of any symptoms of ILI, to contact the
site and to take a nasal sample at home at the time of symptom onset. Calls will also check for any SAEs and associated concomitant medications since the previous visit or
telephone contact. Details of these procedures are described in Section 8.1.1, ILI Procedures.
n. 
Ruler and thermometers will be distributed at Day 1 visit, and training will be conducted by the site staff at both Day 1 and Day 57 visits.
o. 
Review of diary entries with participants and grading of symptoms must be done by a qualified and delegated site staff member under the oversight of the investigator or a
delegated physician. After review of the diary entries with the participant, the investigator or qualified delegate, will complete their own assessment and document in the relevant
sections of the eCRF.
p. 
In case site staff are able to complete all required screening procedures and determine participant eligibility on the same day (including review of required clinical laboratory
results), the screening visit and the Day 1 visit (first vaccination) may occur on the same day (Day 1), and repeat of Day 1 procedures (including physical examination, vital
signs, urine pregnancy test, hematology and clinical chemistry) is not required.
AE = adverse event; d = day; Flu-iiQTM = Influenza Intensity and Impact Questionnaire; HAI = hemagglutination inhibition; ICF = informed consent form; ILI = influenza-like illness;
immuno. = immunogenicity; mo = month; SAE = serious adverse event; vac = vaccination; SAM = Synthetic Absorptive Matrix strips.

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2. 
INTRODUCTION
Study Vaccine
A candidate vaccine covering Influenza A Group 1 that is composed of INFLUENZA G1 mHA
(with or without Al(OH)3 adjuvant) has shown promise in nonclinical animal models of influenza
and will be assessed in this study.
 
INFLUENZA G1 mHA (JNJ-67920320) is an Influenza A Group 1 (G1) hemagglutinin (HA)
stem-derived protein vaccine antigen (mini-HA) derived from H1N1 A/California/07/2009
virus strain.
For the most comprehensive nonclinical and clinical information regarding INFLUENZA G1
mHA, refer to the latest version of the Investigator's Brochure (IB) for INFLUENZA G1 mHA.
The term "sponsor" used throughout this document refers to the entities listed in the Contact
Information page(s), which will be provided as a separate document.
The term "participant" throughout the protocol refers to the common term "subject".
Naming Conventions
Different naming conventions are being used for vaccine components. The following components
will be used in the current study (VAC21148FLZ1001):
JNJ-number 
Name 
Description
JNJ-67920320 
INFLUENZA G1 mHA  
Group 1 mini-HA protein
N/A  
Al(OH)3 
Aluminum hydroxide adjuvant
The component names will be used throughout the document to refer to the different vaccine
components.
Safety Data Supporting Dose Selection for the INFLUENZA G1 mHA Protein
To date, INFLUENZA G1 mHA has not been tested in humans. Based on previous clinical
experience in other vaccine programs by the sponsor, it is anticipated that the vaccine may be well
tolerated. The dose levels of 
 and 
 of INFLUENZA G1 mHA were chosen based on
the safety and immunogenicity profile of recombinant RSV preF proteins given at doses of 150 µg
in approximately 8,499 participants aged 60 years and older in other studies up to 27 October 2021
by the sponsor (sponsor internal data).
2.1. 
Study Rationale
Influenza is a worldwide public health problem, responsible for significant morbidity and
mortality, as well as a significant resource burden on countries. In a typical year, about 3 to
5 million cases of severe influenza illness and about 290,000 to 650,000 deaths are estimated to
occur worldwide (WHO  2018). In the United States (US), more than 200,000 patients are
hospitalized as a result of seasonal influenza-associated illnesses each year (CDC October 2021),
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and about 90% of influenza-associated deaths occur among adults aged 65 years and older
(CDC 2010).
Seasonal influenza vaccine effectiveness is generally variable and current seasonal vaccines do not
cover all circulating strains in a matched, and even fewer in a mismatched season. Furthermore,
seasonal vaccines must be adapted to current circulating strains (often yearly) based on World
Health Organization (WHO) recommendations and by hemisphere. The vaccine with superior
efficacy data in the elderly (Sanofi Fluzone® High-Dose) provides only 40-60% protection against
clinical influenza (Diazgranados 2014). Overall, these data support the importance of developing
an effective universal influenza vaccine for certain populations, such as the elderly.
One of the reasons for the limited efficacy provided by current influenza vaccines is the fact that
they induce antibodies to the variable head domain of HA. Improving breadth by induction of
antibodies against the more conserved stem domain ofHA will lead to an improvement of overall
vaccine efficacy. A desired profile of a universal influenza vaccine includes: (1) inducing high
titers of broadly neutralizing antibodies (bnAbs) and antibodies with additional Fc-mediated
functionality such as antibody-dependent cell-mediated cytotoxicity  (ADCC) directed against
epitopes in the more conserved HA stem; (2) inducing durable immune responses; (3) protecting
against all human influenza strains; (4) to be safe and well tolerated.
There are different types of bnAbs. Some that bind and, to a certain extent, neutralize all influenza
viruses are fairly rare in the human population. In addition, antibodies have been found which bind
a subset of HA molecules within influenza A. Binding of these antibodies aligns with the 2 distinct
groups of HA sequences seen in the phylogenic tree. Based on this finding and supported by
nonclinical data generated by the sponsor with early stem-only vaccine antigens, it was determined
that to provide broad protection against all circulating influenza viruses, the final universal
influenza vaccine should include 3 HA-based antigens: one for responses against influenza A
Group 1 viruses (eg, H1), one against influenza A Group 2 (eg, H3) and one against influenza B.
The sponsor has chosen to first advance the antigen for Group 1 to obtain clinical proof-of-concept
with this monovalent vaccine before introducing the other 2 molecules in subsequent clinical
studies.
As part of the further development of the Uniflu vaccine, the sponsor plans to conduct this
Phase 1/2a 
FIH 
safety 
and 
reactogenicity 
study 
in 
healthy 
participants 
(study
VAC21148FLZ1001). The mini-HA antigen will be used as a soluble, purified, recombinant
protein (INFLUENZA G1 mHA). To maximize the magnitude of the antibody titers, the protein
antigen will be adjuvanted with aluminum hydroxide (Al(OH)3).
The study is designed to determine a regimen for further clinical development in adults based on
safety and immunogenicity data. The selected regimen should have a favorable safety profile and
induce immune responses with desired magnitude and functionality, as supported by the secondary
endpoints described in Section 3, Objectives and Endpoints.

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2.2. 
Background
2.2.1. 
Nonclinical Studies
Nonclinical Pharmacology
Nonclinical studies were performed in different species to test the immunogenicity and protective
efficacy of different vaccine candidates, leading to the selection of the current vaccines for the
Phase 1/2a clinical study.
The Al(OH)3 adjuvanted INFLUENZA G1 mHA vaccine was immunogenic in influenza-naïve
mice, ferrets and nonhuman primates. The vaccine induced HA (stem)-specific humoral responses
and neutralizing antibodies against a broad panel of Influenza A Group 1 strains in ferrets and
nonhuman primates. A homologous 2-dose regimen with Al(OH)3 adjuvanted INFLUENZA G1
mHA gave protection in murine efficacy models using H1N1 A/Brisbane/59/2007 or H5N1
A/Hong Kong/156/1997 challenge strains. A homologous 2-dose regimen  with Al(OH)3
adjuvanted INFLUENZA G1 mHA was protective (as defined by a significant reduction in lung
infectious viral titers) in naïve ferrets after non-lethal challenge with a pandemic H1N1
A/Netherlands/602/2009 strain. In influenza virus (seasonal H1N1 A/Brisbane/59/2007) pre-
exposed ferrets, a single vaccination with Al(OH)3 adjuvanted INFLUENZA G1 mHA was
immunogenic and gave protection against challenge with the H5N1 A/Indonesia/05/2005 strain.
Nonclinical Safety
Biodistribution
For recombinant protein vaccines (such as the INFLUENZA G1 mHA), pharmacokinetics studies
(including biodistribution studies) are not normally needed (WHO 2005).
Toxicology
The nonclinical safety of the vaccine components (INFLUENZA G1 mHA and Al(OH)3 adjuvant)
has been tested in a Good Laboratory Practice (GLP) compliant, IM repeat-dose toxicity and local
tolerance study in rabbits. Full human doses of the various vaccine components and combinations
thereof were tested using a N+1 dosing regimen compared to the intended clinical study. The
effects observed were the expected physiological/immunological responses to the injection of a
vaccine and no adverse vaccine-related findings were noted in this study.
Per WHO Guidelines on Nonclinical Evaluation of Vaccines (WHO 2005), genotoxicity and
carcinogenicity studies have not been performed. The components of the study vaccine are not
expected to have genotoxic or carcinogenic potential.
2.2.2. 
Clinical Studies
This will be the FIH study for the INFLUENZA G1 mHA protein; therefore, no clinical experience
is available.

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2.3. 
Benefit-Risk Assessment
More detailed information about the known and expected benefits and risks of INFLUENZA G1
mHA may be found in the latest version of the IB.
2.3.1 Risks Related to Study Vaccination
This clinical study is a FIH study for the INFLUENZA G1 mHA protein vaccine. In this study, it
will be the first time that this vaccine will be evaluated in humans.
The following risks for VAC21148 (INFLUENZA G1 mHA [with or without Al(OH)3 adjuvant])
will be monitored during the study and are specified in the protocol:
Risks Related to INFLUENZA G1 mHA
This study will be the FIH study for INFLUENZA G1 mHA. No clinical data are available to date.
For the most comprehensive nonclinical information regarding INFLUENZA G1 mHA, refer to
the latest version of the IB.
General Risks Related to Vaccination
In general, IM injection may cause local itching, warmth, pain, tenderness, erythema/redness,
induration, swelling, arm discomfort, or bruising of the skin. Participants may exhibit general signs
and symptoms associated with IM injection of a vaccine and/or placebo, including fever, chills,
rash, myalgia, nausea/vomiting, headache, dizziness, arthralgia, general itching, and fatigue. These
side effects will be monitored, but are generally short-term (typically lasting 2 to 3 days) and do
not require treatment.
Syncope can occur in association with administration of injectable vaccines. Syncope can be
accompanied by falls. Procedures should be in place to avoid falling injury. If syncope develops,
participants should be observed until the symptoms resolve. Fear of injection might lead to fainting
and fast breathing.
Participants may have an allergic reaction to vaccination. An allergic reaction may cause a rash,
urticaria or even anaphylaxis. Severe reactions are rare. Participants with a history of severe
allergic reaction, anaphylaxis or other serious adverse reactions to vaccines or vaccine excipients
(specifically the excipients of the study vaccine) will be excluded from the study.
After each vaccination, participants will remain at the study site for at least 30 minutes and will be
closely observed by site staff. Necessary emergency equipment and medications must be available
in the clinic to treat severe allergic reactions.
Risks Related to Aluminum
Aluminum is one of the most common metals found in nature and is present in air, food, and water.
Aluminum salts, such as aluminum hydroxide, aluminum phosphate, and aluminum potassium
sulphate have been used safely in vaccines for more than 70 years. A few studies have reported an

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association between vaccines containing aluminum adjuvants and persistent nodules at the
injection site, at an estimated rate of 0.03% to 0.83% (Baylor 2002; Bergfors 2003; Bergfors 2014;
Netterlid 2004). Two studies examining infant exposure to aluminum from both diet and vaccines
concluded that aluminum adjuvants at the levels included in vaccines are well below the calculated
safe body burden (Keith 2002; Mitkus 2011). A 2017 review found that current data do not support
a causal relationship between aluminum-containing vaccines and a variety of autoimmune
disorders (Ameratunga 2017).
Pregnancy and Birth Control
The effect of the study vaccine on a fetus or nursing baby is unknown.
Female participants of childbearing potential will be required to agree to practice an acceptable
effective method of contraception and agree to remain on such a method of contraception from
providing consent until 3 months after receiving study vaccine (see Section 5.1). Participants who
are pregnant or breastfeeding will be excluded from the study. Participants who become pregnant
during the study may not receive further study vaccine, but will remain in the study and will
continue to undergo all procedures for surveillance and all safety follow-up as outlined in the
protocol for all participants (see Section  7.1 Discontinuation of Study Vaccine). Follow-up
information regarding the outcome of the pregnancy will be required.
Because the effect on sperm is unknown, male participants must inform the study-site personnel if
their partner becomes pregnant during the study. Follow-up information regarding the outcome of
the pregnancy will be requested upon the consent provided by the partner.
Participants with Immunosuppression/Reduced Immune Response
Participants with abnormal function of the immune system will be excluded from the study.
Limited evidence indicates that inactivated vaccines (or non-replicating viral vaccines) generally
have the same safety profile in immunocompromised patients as in immunocompetent individuals.
However, the magnitude, breadth, and persistence of the immune response to vaccination may be
reduced or absent in immunocompromised persons.
Risks from Blood Draws
Blood drawing may cause pain, tenderness, bruising, bleeding, dizziness, vaso-vagal response,
syncope, and rarely, infection at the site where the blood is taken. Participants with
contraindications to IM injections and blood draws (eg, bleeding disorders) will be excluded.
Risks from Genetic Testing
Genetic testing can be used to provide information about how susceptible participants are to certain
diseases, as well as to provide other unique personal identifiable information. Used
inappropriately, this information could be discriminatory (for example, by insurance companies).
The results will be coded to protect participant identity. The results are for exploratory and future
research purposes only and will not be provided to the participant.

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Risks from Nasal Swab Sampling
The collection of specimens by nasal swabs can cause or exacerbate irritation of the nasal mucosa,
which can result in bleeding/epistaxis.
Concomitant Vaccination
Concomitant vaccination might have an influence on both the safety profile and immunogenicity
of the studyvaccine. Likewise, the studyvaccine might have an influence on both the safety profile
and immunogenicity of any concomitant vaccination. As a result, licensed live attenuated vaccines
should be given at least 28 days before or after vaccination. Other licensed (not live) vaccines (eg,
influenza, tetanus, hepatitis A, hepatitis B, rabies, coronavirus disease 2019) should be given at
least 14 days before or after vaccination to avoid potential confusion of adverse reactions and
potential immune interference. Seasonal influenza vaccines should not be given within 4 months
before planned administration of the first study vaccination until the end of the study. If a vaccine
is indicated in a postexposure setting (eg, rabies or tetanus), it must take priority over the study
vaccine.
Unknown Risks
There may be other risks that are not known. If any significant new risks are identified, the
investigators and participants will be informed.
2.3.2 Benefits Related to Study Vaccination
Participants may benefit from clinical testing and physical examination, including the monitoring
of influenza-like illness if it arises; others may benefit from the knowledge that they may aid in
the development of a universal influenza vaccine.
The clinical benefits of the study vaccine have yet to be established. Currently, there are no
effective universal vaccines for influenza and no efficacy can be concluded from current data. The
overall benefit and risk balance for individual participants thus cannot be ascertained. Participants
must be informed that this vaccine has not yet been proven to be effective, and it should be assumed
that it is not the case until clinical studies are conducted that demonstrate its effectiveness.
2.3.3 Benefit-Risk Assessment Related to Study Vaccination
Based on the available data and proposed safety measures, the overall benefit-risk assessment for
this clinical study is considered acceptable for the following reasons:
 Only participants who meet all inclusion criteria and none of the exclusion criteria (specified in
Section 5, Study Population) will be allowed to participate in this study. The eligibility criteria
include adequate provisions to minimize the risk and protect the well-being of participants in
the study.
 Safety will be closely monitored throughout the study:
 In general, safety evaluations will be performed at scheduled visits during the study, as
described in Section 1.3, Schedule of Activities.

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 After each vaccination, participants will remain at the study site for at least 30 minutes and
will be closely observed by site staff. Necessary emergency equipment and medications
must be available in the clinic to treat severe allergic reactions. Participants will use a diary
to document solicited signs and symptoms. Details are provided in Section  8.2, Safety
Assessments and Section 8.3, Adverse Events, Serious Adverse Events, and Other Safety
Reporting.
 The investigator or the designee will document unsolicited adverse events (AEs) as
indicated in Section 8.3, Adverse Events, Serious Adverse Events, and Other Safety
Reporting and Section 10.4, Appendix 4 Adverse Events: Definitions and Procedures for
Recording, Evaluating, Follow-up, and Reporting.
 Any serious clinically significant abnormalities (including those serious events persisting
at the end of the study/early withdrawal) will be followed by the investigator until
resolution or until a clinically stable endpoint is reached.
 Several safety measures are included in this protocol to minimize the potential risk to
participants, including the following:
 Sentinel participants will be evaluated for safety before extending enrollment in each cohort.
The blinded 48-hour post-vaccination safety data in these sentinel participants will be
reviewed by the principal investigator(s) (PIs) and sponsor’s study responsible physician
(SRP)/medical officer. Randomization of additional participants will be paused until this 48-
hour sentinel safety evaluation is completed.
 For both cohorts, an internal data review committee (DRC) will review blinded a 7-day post-
first dose safety in participants in the sentinel subset and safety ramp-up subset. Additional
participants will only be enrolled following a favorable decision by the DRC. For both
cohorts, the DRC will also review blinded b 7-day post-second dose safety in participants in
the sentinel subset and safety ramp-up subset. Participants in the high-dose protein
(INFLUENZA G1 mHA 
 groups will only be given the second dose following a
favorable decision by the DRC regarding the low dose (INFLUENZA G1 mHA
 There are pre-specified rules for all participants, that would result in pausing of further
vaccinations if predefined conditions occur, preventing exposure of new participants to study
vaccine until the DRC reviews all safety data (see Committee Structure in Section 10.3,
Appendix 3, Regulatory, Ethical, and Study Oversight Considerations).
 Participants will be discontinued from study vaccine for the reasons included in Section 7.1,
Discontinuation of Study Vaccine.
 Contraindications to vaccination are included in Section 7.1.1, Criteria for Temporarily
Delaying Study Vaccine Administration.
a 
The DRC will review blinded data first but may review unblinded data if deemed necessary.
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3. 
OBJECTIVES AND ENDPOINTS
Objectives 
Endpoints
Safety
 
Primary 
objective: 
To 
evaluate 
safety/
reactogenicity of INFLUENZA G1 mHA, with or
without Al(OH)3 adjuvant, in participants ≥18 to
≤45 years of age.
 
Primary endpoints:
 
Occurrence, 
severity, 
duration 
and
relationship of solicited local and systemic
AEs for 7 days after each vaccination.
 
Occurrence, 
severity, 
duration 
and
relationship of unsolicited AEs for 28 days
after each vaccination.
 
Occurrence and relationship of SAEs from
first vaccination to the end of the study.
Immunogenicity
 
Secondary objective: To evaluate the humoral
immune responses to INFLUENZA G1 mHA,
with or without Al(OH)3 adjuvant in participants
≥18 to ≤45 years of age.
 
Secondary endpoint: The magnitude of antibodies
binding to the stem or the full-length HA protein as
measured by enzyme-linked immunosorbent assay
(ELISA).
 
Exploratory objectives: To further assess the
immune responses elicited by INFLUENZA G1
mHA, with or without Al(OH)3 adjuvant in
participants ≥18 to ≤45 years of age.
 
Exploratory endpoints may include, but are not
limited to assessing:
 
Vaccine-induced changes to the breadth of
the antibody response within Group 1 or
beyond as measured by ELISA using full-
length HA proteins indicative of clade or
group coverage
 
HA stem- or epitope-specificity as measured
by ELISAs using HA stem protein or
competition ELISAs using bnAbs or HA
proteins
 
Functional characterization of the antibody
response as measured by assays assessing Fc-
mediated functions (eg, Fc gamma receptor
[FcγR] binding assays to the stem or full-
length HA protein, or antibody-dependent
cytotoxicity  assay, or antibody-dependent
cellular 
phagocytosis 
assay), 
HA
conformational change assays, or other
assays
 
Vaccine-induced changes to the functional
breadth of the antibody response within
Group 1 or beyond as measured by virus
neutralization assays or serum transfer into
animal challenge models
 
Molecular characterization of the antibody
response as measured by assays assessing the
epitope-specificity, glycosylation status, or
other characteristics of the antibody (eg, by
systems serology arrays)
 
Vaccine-induced changes in innate immune
responses by transcript- or cytokine profiling
 
Vaccine-induced changes in gene expression
profiles 
by 
ribonucleic 
acid 
(RNA)
sequencing or other transcriptional profiling
methods, including but not limited to

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Objectives 
Endpoints
sequencing for T cell receptor or B cell
receptor repertoire analysis
 
Nasal antibody response as measured by
immunoglobulin (Ig) G or IgA ELISA in
nasal secretions
 
Exploratory objective: To evaluate longevity of
immune responses elicited by INFLUENZA G1
mHA, with or without Al(OH)3 adjuvant in
participants aged ≥18 to ≤45 years.
 
Exploratory endpoint: The magnitude and
functionality of antibodies binding to the stem or
the full-length HA protein of various strains as
measured by ELISA, virus neutralization assays,
and FcγR binding assays on Days 238 and 365.
 
Exploratory objective: To evaluate the immune
responses in participants with confirmed influenza
infection.
 
Exploratory endpoint: During the influenza
season:
 
Immune responses by assays included for
secondary and exploratory immunogenicity
endpoints
Virology
 
Exploratory objective: To monitor symptoms of
influenza-like illness (ILI) via the Influenza
Intensity and Impact Questionnaire (Flu-iiQTM) as
well 
as 
rapid 
molecular 
diagnosis 
and
characterization to evaluate infection rate in
participants aged ≥18 to ≤45 years and in relation
to immunological markers.
 
Exploratory endpoints: During the influenza
season:
 
Signs and symptoms of ILI
 
Confirmation of infection by reverse
transcriptase polymerase chain reaction
(RT-PCR) or response to influenza-like
infection by serology
Refer to Section 8, Study Assessments and Procedures for evaluations related to endpoints.
HYPOTHESIS
No formal statistical hypothesis is to be tested. The study will evaluate whether INFLUENZA G1
mHA, with or without Al(OH)3 adjuvant, is safe, well tolerated and immunogenic in healthy adults
aged ≥18 to ≤45 years.
4. 
STUDY DESIGN
4.1. 
Overall Design
This is a randomized, double-blind, placebo-controlled, FIH Phase 1/2a study to evaluate safety,
reactogenicity and immunogenicity of a universal influenza (Uniflu) vaccine  INFLUENZA G1
mHA in healthy male and female adults aged ≥18 to ≤45 years.
A target of 170 participants will be enrolled in this study. The study design includes 2 sequential
cohorts comparing INFLUENZA G1 mHA (with or without Al(OH)3 adjuvant) at 2 dose levels
(see Table 1).
Table 1: 
Study Design: VAC21148FLZ1001
Cohort 
Group 
N 
Day 1 
Day 57
1 
1 
25 
INFLUENZA G1 mHA
 
INFLUENZA G1 mHA
2 
25 
INFLUENZA G1 mHA
Al(OH)3 
INFLUENZA G1 mHA
Al(OH)3
3 
10 
Placebo 
Placebo
2 
4 
25 
INFLUENZA G1 mHA
 
INFLUENZA G1 mHA
5 
25
INFLUENZA G1 mHA 
 
Al(OH)3 
INFLUENZA G1 mHA 
Al(OH)3
6 
25 
INFLUENZA G1 mHA
 
Placebo
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7 
25 
INFLUENZA G1 mHA 
Al(OH)3
Placebo
8 
10 
Placebo 
Placebo
TOTAL: 
170
Al(OH)3 = aluminum hydroxide (aluminum content at 0.75 mg/dose); N = number of participants.
Thestudyduration (excluding screening)willbe approximately 365 days per participant. The study
comprises a maximum 42-day screening period, study vaccination (active or placebo) with a 2-
dose (on Day 1 and Day 57) regimen, a minimum 28-day follow-up period after each vaccination,
and a long-term follow-up period until 1 year after the first vaccination. The end of the study is
defined as the last participant’s last visit 12 months after the first vaccination.
A diagram of the study design is provided in Section 1.2, Schema.
An internal DRC, consisting of members that are not directly involved in the study conduct, data
management, or statistical analysis, will be commissioned for this study to evaluate (blinded)
safety and reactogenicity data on a regular basis. Refer to Committees Structure in Section 10.3,
Appendix 3, Regulatory, Ethical, and Study Oversight Considerations for details.
First-dose Cohort 1
In Cohort 1, 60 participants aged ≥18 to ≤45 years will be enrolled in a staggered approach with
safety evaluations in place before extending enrollment in this cohort and progressing to Cohort
2. Initially, 5 sentinel participants will be enrolled and randomized; 2 participants in Groups 1 and
2 and 1 participant in Group 3 (placebo) will receive a single IM injection of either 
INFLUENZA G1 mHA, 
 INFLUENZA G1 mHA adjuvanted with Al(OH)3, or placebo on
Day 1. Sentinel participants will be contacted by telephone 48 hours post-vaccination to collect
safety information. The blinded 48-hour post-vaccination safety data in these 5 sentinel
participants will be reviewed by the PI(s) and SRP. Randomization of additional participants will
be paused until this 48-hour sentinel safety evaluation is completed (Figure 2).
In the absence of any clinically significant findings, upon decision by PI(s) and SRP, an additional
12 participants will be enrolled (5 additional participants in Groups 1 and 2 and 2 additional
participants in Group 3 [placebo] as safety ramp-up subset; Figure 2).
DRC will review blinded safety data of the initial 17 participants 7 days after the first vaccination.
DRC review will be held to review available safety data of initial participants enrolled before these
participants can receive the second vaccination. Further randomization in Cohort 1 will be paused
until the DRC safety evaluation is completed. In the absence of findings from the DRC following
the first vaccination, the remaining 43 participants in Cohort 1 will be enrolled in a 18:18:7 ratio
and randomization in Cohort 2 may be initiated simultaneously (Figure 2).
First-dose Cohort 2
In Cohort 2, 110 participants aged ≥18 to ≤45 years will be enrolled in a staggered approach with
safety evaluations in place before extending enrollment in this cohort. Initially, 5 sentinel
participants will be enrolled and randomized; 1 participant in each of the 5 groups (Groups 4 to 8
[including 1 placebo]) will receive a single IM injection of either 
 INFLUENZA G1 mHA;
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 INFLUENZA G1 mHA adjuvanted with Al(OH)3; or placebo on Day 1. Sentinel
participants will be contacted by telephone 48 hours post-vaccination to collect safety information.
The blinded 48-hourpost-vaccination safety data in these 5 sentinel participants will be reviewed
by the PIs and SRP. Randomization of additional participants will be paused until this 48-hour
sentinel safety evaluation is completed (Figure 2).
In the absence of any clinically significant findings, upon decision by PI(s) and SRP, an additional
10 participants will be enrolled and randomized in parallel (2 additional participants in Groups 4
to 8 [including 2 placebo]) as safety ramp-up subset (Figure 2).
DRC will review blinded safety data of the 15 participants in Cohort 2, 7 days after the first
vaccination. DRC review will be held to review available safety data of initial participants enrolled
before these participants can receive the second vaccination. Further randomization in Cohort 2
will be paused until the DRC safety evaluation is completed. In the absence of findings from the
DRC following the first vaccination, the remaining 95 participants in Cohort 2 will be enrolled in
a 22:22:22:22:7 ratio (Figure 2).
Figure 2: 
Participant Enrollment and First Dose Safety Strategy
DRC = data review committee; PI = principal investigator; SRP = study responsible physician.
* Sentinel participants will be contacted 48 hours post-vaccination by telephone to collect safety information.
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Second-dose Safety
In alignment with the first-dose safety strategy, post-second dose 48-hour (sentinel participants)
and 7-day safety assessments (participants in the sentinel subset and safety ramp-up subset) will
be monitored by the PI(s) and SRP, and the DRC, respectively a (see Figure 2). The sequence in
which participants in the sentinel subset and the safety ramp-up subset are vaccinated should be
similar for Dose 1 and Dose 2. Administration of the second dose will also be staggered to allow
safety assessments to be made 7 days after the second dose in participants in the safety ramp-up
subset receiving low-dose protein (INFLUENZA G1 mHA
 before administering the second
dose to participants in the high-dose protein (INFLUENZA G1 mHA 
 groups. In the
absence of clinically relevant findings and following the decision by the DRC, dosing the
remaining participants will continue as described above.
For both cohorts, the DRC will review blinded b 7-day post-first dose as well as post-second dose
safety. Safety data for review will include solicited and unsolicited AEs, SAEs, and available
laboratory assessments. If any pre-specified study vaccination pausing rule is met, vaccinations
will be paused, and a DRC meeting will be convened. For details on the pausing rules, see
Section 6.8, Study Pausing Rules. In addition, the DRC will also evaluate safety data over the
course of the study and review any events that meet a specific study vaccine pausing rule or any
other safety issue that may arise.
Study Procedures
After each vaccination, participants will remain under observation at the study site for at least
30 minutes for presence of any acute reactions and solicited events. In addition, participants will
record solicited signs and symptoms in a diary for 7 days post-vaccination, beginning each study
vaccine dosing day. Participants will be given a thermometer, ruler and daily assessment
(participant) diary with instructions for the proper recording of events. Oral temperatures should
be taken at approximately the same time each day,c and additional temperature measurements may
be taken if a participant does not feel well. Study-site personnel will collect and review participant
diary information and confirm the entries at subsequent site visits.
AEs will be collected as outlined in Section 8.3.1, Time Period and Frequency for Collecting
Adverse Event and Serious Adverse Event Information.
a 
In case a participant in the sentinel subset or the safety ramp-up subset withdraws from the study prior to receiving
Dose 2 or receives Dose 2 outside the prespecified visit window, the post-second dose 48-hour safety review by
the PI(s) and SRP, as well as the 7-day safety review by the DRC will be performed as scheduled based on the
available data.
b
The DRC will review blinded data first but may review unblinded data if deemed necessary.
c
Temperature 7 days after each vaccination may be collected earlier on the Day 8 or Day 64 to coincide with the
clinic visit.
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All AEs, including any that are ongoing at 28 days after each dose, will be followed until clinical
resolution or stabilization. Concomitant therapies will be collected from the signing of the ICF
until 28 days after the first vaccination and from the second vaccination through the following
28 days, and additionally outside of these periods when associated with an SAE.
Blood and urine samples for clinical laboratory assessments will be collected as indicated in
Section 1.3 Schedule of Activities and Section 10.6, Appendix 6: Clinical Laboratory Tests.
Blood will be collected from all participants to assess humoral immune responses pre-vaccination
on each dosing day, at 7 days and at 28 days after each dose, at 6 months after the second dose,
and at 12 months after the first dose (or at the early exit visit if the participant prematurely
terminates the study without withdrawing consent a).
Participants should record signs and symptoms of influenza during the influenza season using a
specific Influenza Intensity and Impact Questionnaire (Flu-iiQTM) and an ILI form. Participants
will be informed of the timing of the start and end of the influenza season in accordance with the
country/region-specific influenza local surveillance system. Procedures for Flu-iiQTM
questionnaire and ILI form completion are described in Section 8.1.1, ILI Procedures. The Flu-
iiQTM questionnaire and ILI form will be the primary source for influenza monitoring. Participants
will be contacted by telephone or other means of communication every 14±3 days (unless a
planned clinic visit has occurred or will occur within 14 days). Calls will remind the participants
to complete the Flu-iiQTM questionnaire and ILI form in the event of any symptoms of influenza
infection, to contact the site at the time of symptom onset, and to take a nasal swab at home
preferably on the day of symptom onset or the day thereafter (ILI Days 1-2). Calls will also check
for any SAEs and associated concomitant medications since the previous visit or telephone contact.
Full details of ILI procedures, including the collection of nasal swabs are provided in Section 8.1.1,
ILI Procedures.
The presence of influenza virus infection will be assessed by qualified site staff by RT-PCR
diagnostics and/or rapid-PCR detection (eg, by Cepheid GeneXpert®) on the nasal swab samples.
Seasonal Influenza Vaccination
Seasonal influenza vaccination is not allowed during a time window starting 4 months prior to
Dose 1 until the end of the study. Participants should be willing to forego any influenza vaccination
during the entire study period and will have to consent to this. This will allow to assess longevity
of the immune response without interference of a seasonal influenza vaccine. Although seasonal
influenza vaccination is recommended in the US but not generally recommended in Europe for
participants in this age group (Grohskopf 2019), several placebo-controlled clinical studies have
been conducted in this age group (Treanor 2007; Treanor 2011). All participants will be closely
a 
Immunogenicity blood samples will only be taken if early exit is at least 14 days after the previous immunogenicity
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monitored for symptoms of influenza infection (using the Flu-iiQTM questionnaire) to ensure that
early diagnosis and treatment can be provided if necessary. In this age group, influenza infections
are generally mild with non-serious consequences.
4.2. 
Scientific Rationale for Study Design
Dose Selection
The rationale behind the selection of the doses is described in Section 4.3, Justification for Dose.
Regimen Selection
In Cohort 1, initial safety and immunogenicity assessment of a 2-dose regimen of INFLUENZA
G1 mHA (
 with or without Al(OH)3 adjuvant, will be performed.
In Cohort 2, safety and immunogenicity of high-dose (
 INFLUENZA G1 mHA (with and
without Al(OH)3 adjuvant) administered in a 2-dose or single-dose regimen will be assessed.
The vaccination regimens are with administration of study vaccination (active or placebo) on Day
1 and Day 57 (8-week interval). The interval is based on data from other studies by the sponsor in
which higher antibody responses were observed in studies with an 8-week interval regimen
compared to studies with a 4-week interval regimen  (Milligan 2016). A longer (eg, 12-week
interval) regimen was not considered for the current study because this would be impractical for
an influenza vaccine.
Blinding, Control, Study Phase/Periods, Intervention Groups
A placebo control will be used to establish the frequency and magnitude of changes in clinical
endpoints that may occur in the absence of active intervention. Randomization will be used to
minimize bias in the assignment of participants to intervention groups, to increase the likelihood
that known and unknown participant attributes (eg, demographic and baseline characteristics) are
evenly balanced across intervention groups, and to enhance the validity of statistical comparisons
across intervention groups. Blinded intervention will be used to reduce potential bias during data
collection and evaluation of clinical endpoints.
Biomarker Collection and Limited Genetic Testing
It is recognized that genetic variation can be an important contributory factor to interindividual
differences in response to vaccination. Limited genetic testing (eg, gene expression profiling) may
help to explain interindividual variability in clinical outcomes and may help to identify population
subgroups that respond differently to vaccination. The goal of the gene expression profiling
component is to collect RNA to allow the identification ofgenetic factors that may influence the
safety, reactogenicity and immunogenicity of INFLUENZA G1 mHA.
Biomarker samples will be collected to evaluate the immunogenicity of INFLUENZA G1 mHA
or help to explain interindividual variability in clinical outcomes or may help to identify population
subgroups that respond differently to vaccination. The goal of the biomarker analyses is to evaluate
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the immunogenicity of INFLUENZA G1 mHA and aid in evaluating the intervention-clinical
response relationship.
4.2.1. 
Study-Specific Ethical Design Considerations
Potential participants will be fully informed of the risks and requirements of the study and, during
the study, participants will be given any new information that may affect their decision to continue
participation. They will be told that their consent to participate in the study is voluntary and 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 participants who are fully able to understand the risks, benefits,
and potential AEs of the study, and provide their consent voluntarily will be enrolled.
The primary ethical concern is that this study will be performed in healthy adult participants who
will receive no benefit from participation in the study, except for compensation for the time and
inconveniences that may arise from participation in the study. Refer to Section 2.3, Benefit-risk
Assessment for details on potential and known benefits and risks, and for the safety measures taken
to minimize risk to participants.
The total blood volume to be collected is considered to be an acceptable amount of blood to be
collected over this time period from the population in this study based upon the US Department of
Health and Human Services Office for Human Research Protections, and US Food and Drug
Administration (FDA) guidelines of 550 mL in any 8-week period (OHRP 1998; FDA 1998).
4.3. 
Justification for Dose
The 
 dose was selected as the initial dose for INFLUENZA G1 mHA as this is in line with
the Influenza A Group 1 HA dose in the licensed Flublok vaccine, which contains 
 of each
HA and is well tolerated (Cox 2015). Furthermore, data from other programs by the sponsor
showed this dose of protein to be safe (sponsor internal data). However, it is anticipated that doses
higher than this will be required to achieve optimal immune responses, due to the inherent lower
immunogenicity of the HA stem domain compared to the head domain of the molecule (Tan 2019).
Therefore, the 
 dose was selected as it represents an approximately 0.5 log increase over
the 
 dose, representing a meaningful difference given the biological response and typical
assay variability. As it is anticipated that the final Uniflu vaccine may consist of a mixture of
3 different proteins (covering Influenza A hemagglutinin Group 1, Group 2 and Influenza B), a
dose of 
 per protein in the regimen approaches a practical limit for this vaccine. The dose
levels of 
 and 
 of INFLUENZA G1 mHA to be used were also chosen as the initial
dose based on the safety and immunogenicity profile of recombinant RSV preF proteins given at
doses of 150 µg in approximately 8,499 participants aged 60 years and older in other studies up to
27 October 2021 by the sponsor. These recombinant RSV proteins were given directly mixed with
Ad26-vectored RSV vaccine.
There might be a need for the use of an adjuvant in this vaccine program. As it is the most widely
used adjuvant, Al(OH)3 has been chosen for this study. The Al(OH)3 adjuvant with an aluminum
content of 0.75 mg/dose was chosen to be well within the FDA recommendation of maximal
0.85 mg per dose. Aluminum-containing vaccines have been in use for over 70 years and have
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rarely been associated with SAEs. However, local reactions such as redness, swelling and/or
tenderness at the injection site are common (Eickhoff2002; Jefferson 2004).
4.4. 
End of Study Definition
End of Study Definition
The end of study is considered as the last visit for the last participant in the study. The final data
from the study site will be sent to the sponsor (or designee) after completion of the final participant
visit at that study site, in the time frame specified in the clinical trial agreement.
Participant Study Completion Definition
A participant will be considered to have completed the study if the participant has completed
assessments at Day 365±30 days of the follow-up phase.
Participants who prematurely discontinue study vaccine for any reason before completion of the
vaccination phase can be considered to have completed the study if they have completed follow-
up and the scheduled assessments.
5. 
STUDY POPULATION
Screening for eligible participants will be performed within 42 days before administration of the
study vaccine. Refer to Section 5.4, Screen Failures for conditions under which the repeat of any
screening procedures are allowed.
The inclusion and exclusion criteria for enrolling participants in this study are described below. If
there is a question about these criteria, the investigator must consult with the appropriate sponsor
representative and resolve any issues before enrolling a participant in the study. Waivers are not
allowed.
For a discussion of the statistical considerations of participant selection, refer to Section 9.2,
Sample Size Determination.
5.1. 
Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1. Criterion modified per Amendment 2:
1.1 must sign an ICF indicating that the participant understands the purpose, procedures and
potential risks and benefits of the study, and is willing to participate in the study.
2. Criterion modified per Amendment 2:
2.1 willing and able to adhere to the lifestyle restrictions specified in this protocol.
3. Criterion modified per Amendment 1:
3.1 male or female, ≥18 to ≤45 years of age on the day of signing the ICF and expected to
be available for the duration of the study.
4. Criterion modified per Amendment 1:

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4.1 must be healthy as confirmed by medical history, physical examination, and vital signs
performed at screening.
Note: A participant must be healthy per the investigator’s judgement prior to study
vaccine administration on Day 1 and Day 57.
5. Criterion modified per Amendment 1:
5.1 Criterion modified per Amendment 2:
5.2 contraceptive (birth control) use by female participants should be consistent with local
regulations regarding the acceptable methods of contraception for those participating in
clinical studies. Before randomization, participants who were born female must be either
(as defined in Section 10.2, Appendix 2, Contraceptive Guidance and Collection of
Pregnancy Information):
a. not of childbearing potential
b. of childbearing potential and practicing a highly effective method of contraception and
agreeing to remain on such a method of contraception from signing the informed consent
until 3 months after the last dose of study vaccine. Use of hormonal contraception should
start at least 28 days before the first administration of study vaccine. Highly effective
methods for this study include:
1) hormonal contraception
2) intrauterine device
3) intrauterine hormone-releasing system
4) bilateral tubal occlusion/ligation procedures
5) vasectomized partner (the vasectomized partner should be the sole partner for that
participant)
6) sexual abstinence a
6. Criterion modified per Amendment 1:
6.1 all female participants of childbearing potential must:
a. have a negative highly sensitive serum β-human chorionic gonadotropin (β-hCG)
pregnancy test at screening
b. have a negative urine β-hCG pregnancy test immediately prior to each study vaccine
administration
7. agrees to not donate blood until 3 months after receiving the last dose of study vaccine.
8. must be able to read, understand, and complete questionnaires in the Diary and Flu-iiQTM
questionnaire.
a 
Sexual abstinence is considered an effective method only if defined as refraining from heterosexual intercourse
from signing the informed consent until 3 months after the last dose of study vaccine. The reliability of sexual
abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the
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9. must be willing to provide verifiable identification, have means to be contacted and to contact
the investigator during the study.
10. Criterion added per Amendment 1:
10.1 must be healthy on the basis of clinical laboratory tests performed at screening. If the
results of the laboratory screening tests are outside the laboratory normal reference
ranges and additionally within the limits of toxicity Grade 2 according to the US FDA
toxicity tables in Section 10.5, Appendix 5, Toxicity Grading Scale, the participant may
be included only if the investigator judges the abnormalities or deviations from normal
to be not clinically significant and appropriate and reasonable for the population under
study. This determination must be recorded in the participant’s source documents and
initialed by the investigator.
Note: If laboratory screening tests are out of laboratory normal ranges and deemed
clinically significant, repeat of screening tests is permitted once, using an unscheduled
visit during the screening period to assess eligibility.
5.2. 
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from
participating in the study:
1. contraindication to IM injections and blood draws eg, bleeding disorders.
2. Criterion modified per Amendment 2:
2.1 clinically significant acute illness (this does not include minor illnesses such as diarrhea
or mild upper respiratory tract infection) or temperature ≥38.0ºC (100.4°F) within 24
hours prior to the planned first dose of study vaccine; randomization at a later date is
permitted at the discretion of the investigator and after consultation with the sponsor.a
3. history of malignancy within 5 years before screening (exceptions are squamous and basal
cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is
considered cured with minimal risk of recurrence).
4. Criterion modified per Amendment 1:
4.1 Criterion modified per Amendment 2:
4.2 history ofsevere allergic reaction (eg, anaphylaxis) or other serious adverse reactions to
vaccines or vaccine excipients (specifically the excipients of the study vaccine[s]) (refer
to the IB).
5. Criterion modified per Amendment 1:
5.1 Criterion modified per Amendment 2:
5.2 abnormal function of the immune system resulting from:
a. clinical conditions (eg, autoimmune disease or immunodeficiency) or their treatments
expected to have an impact on the immune response elicited by the study vaccine.
a 
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b. chronic or recurrent use of systemic corticosteroids within 2 months before administration
of study vaccine and during the study.
Note: Ocular, topical, intra-articular, or inhaled steroids are allowed.
c. administration of antineoplastic and immunomodulating agents or radiotherapy expected
to have an impact on the immune response elicited by the study vaccine within 6 months
before administration of study vaccine and during the study.
Note: Topical immunomodulating agents may be allowed upon sponsor approval.
6. Criterion modified per Amendment 1:
6.1 history of acute polyneuropathy (eg. Guillain-Barré syndrome) or chronic idiopathic
demyelinating polyneuropathy.
7. Criterion modified per Amendment 2:
7.1 history of chronic urticaria (recurrent hives), chronic eczema or chronic atopic
dermatitis.
8. Criterion modified per Amendment 2:
8.1 received treatment with immunoglobulins (including monoclonal antibodies) expected
to impact the vaccine-induced immune response in the 2 months or blood products in
the 3 months before the planned administration of the first dose of study vaccine or has
any plans to receive such treatment during the study.
Note: Given that not all immunoglobulins/monoclonal antibodies are expected to impact
the vaccine-induced immune response, the investigator should contact the sponsor to
discuss eligibility of participants on immunoglobulin treatment.
9. Criterion modified per Amendment 1:
9.1 received or plans to receive:
a. Licensed live attenuated vaccines - within 28 days before or after planned administration
of the first or subsequent study vaccination[s].
b. Other licensed (not live) vaccines (not including seasonal influenza vaccines) - within 14
days before or after planned administration of the first or subsequent study vaccination[s].
c. Seasonal influenza vaccines - within 4 months before planned administration of the first
study vaccination until the end of the study. (ie, any individual who requires a seasonal
influenza vaccination for occupational or other reasons will be excluded).
10. Criterion modified per Amendment 1:
10.1 Criterion modified per Amendment 2:
10.2 received an investigational drug or used an invasive investigational medical device
within 30 days or received an investigational vaccine within 6 months before the planned
administration of the first dose of study vaccine, or received an investigational biological
product within 3 months or 5 half-lives, whichever is longer, before the planned study
intervention, or is currently enrolled or plans to participate in another investigational
study or observational clinical study during the course of this study.
Note: Participants can be included if the investigational product received was
subsequently licensed or authorized for emergency use (eg, Emergency Use

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Authorization, Emergency Use Listing, or similar program). Participants with proof of
having received only placebo can also be included. Such participants can, however, only
be included in the absence of follow-up that involves invasive procedures that would
interfere with study requirements or safety follow up.
11. has received a pandemic influenza vaccine (other than H1N1) in a previous pandemic
influenza vaccine study at any time prior to randomization.
12. Criterion modified per Amendment 1:
12.1 pregnant, or breastfeeding, or planning to become pregnant while enrolled in this study
or within 3 months after the last dose of study vaccine. Oocyte donation is prohibited
while enrolled in this study.
13. history of an underlying clinically significant acute or uncontrolled chronic medical condition
or physical examination findings for which, in the opinion of the investigator, participation
would not be in the best interest of the participant (eg, compromise the well-being) or that
could prevent, limit, or confound the protocol-specified assessments.
14. Criterion modified per Amendment 1:
14.1 Criterion modified per Amendment 2:
14.2 had major surgery (eg, impacting immune response to the study intervention, or
requiring a >2-night hospitalization) within 4 weeks before dosing, or will not have fully
recovered from major surgery, or has major surgery planned within 3 months after any
dose of study vaccine administration.
Note: The investigator is encouraged to contact the sponsor to discuss eligibility of
participants in case it’s not clear whether a prior or planned surgery should be
considered major.
15. employee of the investigator or study site with direct involvement in the proposed study or
other studies under the direction of that investigator or study site, as well as family members
of the employees or the investigator, or an employee of the sponsor.
16. has chronic active hepatitis B or hepatitis C infection, per medical history.
17. is positive for HIV, per medical history.
18. has had major psychiatric illness or drug or alcohol abuse which in the investigator’s opinion
would compromise the participant’s safety or compliance with the study procedures.
19. cannot communicate reliably with the investigator.
20. who, in the opinion of the investigator, is unlikely to adhere to the requirements of the study,
or is unlikely to complete the full course of vaccination and observation.
21. has significant scarring, tattoos, abrasions, cuts, or infections over the deltoid region of both
arms that, in the investigator’s opinion, could interfere with evaluation of injection site local
reactions.
22. Criterion added per Amendment 1:
22.1 Criterion deleted per Amendment 2
23. Criterion added per Amendment 1:
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24. Criterion added per Amendment 1:
24.1 Criterion deleted per Amendment 2
Note: Investigators must ensure that all study enrollment criteria have been met prior to the first
vaccination. If a participant's clinical status changes (including any available laboratory results or
receipt of additional medical records) after screening but before the first dose of study vaccine is
given such that the participant no longer meets all eligibility criteria, then the participant must be
excluded from participation in the study. The clinical laboratory results on Day 1 and Day 57 are
not required for eligibilityassessment. Section 5.4, Screen Failures, describes options for retesting.
The required source documentation to support meeting the enrollment criteria are noted in
Section 10.3, Appendix 3, Regulatory, Ethical, and Study Oversight Considerations.
5.3. 
Lifestyle Considerations
Potential participants must be willing and able to adhere to the following lifestyle restrictions
during the course of the study to be eligible for participation:
1. 
Refer to Section 5.2, Exclusion Criteria for details regarding prohibited and restricted
therapy during the study.
2. 
Agree to follow all requirements that must be met during the study as noted in the
Inclusion and Exclusion Criteria (eg, contraceptive requirements).
5.4. 
Screen Failures
Participant Identification, Enrollment, and Screening Logs
The investigator agrees to complete a participant identification and enrollment log to permit easy
identification of each participant during and after the study. This document will be reviewed by
the sponsor study-site contact for completeness.
The participant identification and enrollment log will be treated as confidential and will be filed
by the investigator in the study file. To ensure participant confidentiality, no copy will be made.
All reports and communications relating to the study will identify participants by participant
randomization number and age at initial informed consent. In cases where the participant is not
randomized into the study, the participant screening number, date seen and age at initial informed
consent will be used.
Individuals who do not meet the criteria for participation in this study (screen failure) may be
rescreened at the discretion of the sponsor.
Retesting and Rescreening
Exceptional and limited retesting of abnormal screening values that lead to exclusion are allowed
only once using an unscheduled visit during the screening period (to reassess eligibility).

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If a participant does not meet all inclusion and exclusion criteria (is a screen failure) but at some
point in the future is expected to meet the participant eligibility criteria, the participant may be
rescreened on 1 occasion only. Participants who are rescreened will be assigned a new participant
screening number, undergo the informed consent process, and then restart a new screening phase.
6. 
STUDY VACCINE
6.1. 
Study Vaccine(s) Administered
Participants will be vaccinated at the study site according to the schedule detailed in Section 4.1,
Overall Design (Table 1). For description of the vaccinations, see below.
INFLUENZA G1 mHA, adjuvant and diluent will be manufactured and provided under the
responsibility of the sponsor. Refer to the IB for a list of excipients.
The placebo for this study will be supplied by the sponsor as a commercially available injectable
solution of9 mg/mL Sodium Chloride.
Supplies will be provided by the sponsor in the following configuration:
 
INFLUENZA G1 mHA (JNJ-67920320): supplied at a concentration of 900 µg/mL in a single
use vial, dosed at 
 and 
 with or without Al(OH)3 adjuvant. (Aluminum content at
0.75 mg/dose); 0.5 mL (extractable volume)
 
Placebo: supplied as a sterile solution ofSodium Chloride 9 mg/mL in a single use vial; 10 mL
(filling volume)
 
Aluminum hydroxide adjuvant (Al(OH)3): supplied at a concentration of 3.75 mg/mL in a
single use vial for mixing according to the Investigational Product Preparation Instructions
(IPPI); 1.0 mL (extractable volume)
 
Formulation buffer for INFLUENZA G1 mHA (Diluent Uniflu 1): supplied in a single use
vial for dilution of INFLUENZA G1 mHA according to IPPI; 0.8 mL (extractable volume)
For each participant, every injection will be 1.0 mL in volume. Instructions on study vaccine
preparation (eg, dilution in formulation buffer) into the final dose that participants receive within
each treatment group are outlined in detail in the IPPI.
Preferably the deltoid muscle of the non-dominant upper arm is used to administer the injection.
If an injection cannot be given in either deltoid for the second dose of the vaccination due to a
medical or other contraindication (for example, tattooed upper arms rendering it difficult to assess
site reactogenicity), use alternative locations such as the hip, thigh, or buttocks (to be avoided in
overweight participants). In this case, IM injections in other locations than the upper arm for the
second dose of the vaccination are not considered protocol deviations.
For information on vaccination windows, see Section 8, Study Assessments and Procedures. If a
participant cannot be vaccinated within the allowed window or if the window is missed due to a
study pause (see Section 6.8, Study Pausing Rules), the decision regarding vaccination will be
assessed on a case-by-case basis, upon discussion between sponsor and investigator.
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Study vaccine administration must be captured in the source documents and the electronic case
report form (eCRF).
6.2. 
Preparation/Handling/Storage/Accountability
Preparation/Handling/Storage
All study vaccine must be stored in a secured location with no access for unauthorized personnel
and at controlled temperatures as indicated on the clinical labels. If study vaccine is exposed to
temperatures outside the specified temperature range, all relevant data will be sent to the sponsor
to determine if the affected supplies can be used or will be replaced. The affected study vaccine
must be quarantined and not used until further instruction from the sponsor is received.
Refer to the Site Investigational Product and Procedures Manual (SIPPM) and/or the IPPI for
additional guidance on study vaccine preparation, handling, and storage and stability.
An unblinded pharmacist, or other qualified staff member at the site with primary responsibility
for study vaccine preparation, who will not participate in any other study evaluation, will prepare
the appropriate vial and syringe, labeled with the participant’s identification number, and provide
the blinded syringe to the blinded vaccine administrator who will perform the injection.
All study vaccines were manufactured and packaged in accordance with Current Good
Manufacturing Practice. All study vaccines will be packaged and labeled under the responsibility
of the sponsor. Study vaccine labels will contain information to meet the applicable regulatory
requirements.
No study vaccine can be repacked or relabeled without prior approval from the sponsor.
Accountability
The investigator is responsible for ensuring that all study vaccine received at the site is inventoried
and accounted for throughout the study.
The study vaccine administered to the participant must be documented on the intervention
accountability form. All study vaccine will be stored and disposed of according to the sponsor's
instructions. Study-site personnel must not combine contents of the study vaccine containers.
Study vaccine must be handled in strict accordance with the protocol and the container label, and
must be stored at the study site in a limited-access area or in a locked cabinet under appropriate
environmental conditions. Unused study vaccine must be available for verification by the sponsor's
study site monitor during on-site monitoring visits. The return to the sponsor of unused study
vaccine will be documented on the intervention return form. When the study site is an authorized
destruction unit and study vaccine supplies are destroyed on-site, this must also be documented on
the intervention return form.

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Potentially hazardous materials containing hazardous liquids, such as used ampules, needles,
syringes and vials, should be disposed of immediately in a safe manner and therefore will not be
retained for intervention accountability purposes.
Study vaccine should be dispensed under the supervision of the investigator or a qualified member
of the study-site personnel, or by a hospital/clinic pharmacist. Study vaccine will be supplied only
to participants participating in the study. Returned study vaccine must not be dispensed again, even
to the same participant. Study vaccine may not be relabeled or reassigned for use by other
participants. The investigator agrees neither to dispense the study vaccine from, nor store it at, any
site other than the study sites agreed upon with the sponsor. Further guidance and information for
the final disposition of unused study vaccines are provided in the SIPPM.
6.3. 
Measures to Minimize Bias: Randomization and Blinding
Vaccine Allocation
Procedures for Randomization
Participants will be randomly assigned to 1 of the study vaccine groups based on a computer-
generated randomization schedule prepared before the study by or under the supervision of the
sponsor. The randomization within each cohort will be performed in different steps. Allocation to
the sentinel subset, to the safety ramp-up subset, or to the main study subset will be monitored by
the randomization system which will indicate the specific subset that a participant is included in.
The interactive web response system (IWRS) will assign a unique intervention code, which will
dictate the intervention assignment and matching study vaccine kit for the participant. The
requestor must use his or her own user identification and personal identification number when
contacting the IWRS, and will then give the relevant participant details to uniquely identify the
participant.
If randomized participants are withdrawn from vaccination before the first dose of study vaccine
is administered, additional participants may be recruited to replace these participants at the
discretion of the sponsor. Any replacement participant will be assigned to the same group as the
original (discontinued) participant. The replacement participant’s randomization number will
equal the randomization number of the discontinued participant +1000 (eg, participant 0001 would
be replaced by participant 1001). These additional participants should also be randomized through
IWRS.
In Cohort 1, a total of 60 participants will be enrolled in a staggered approach (Figure 2). Initially,
5 sentinel participants will be randomized; 2 participants to Groups 1 and 2 and 1 participant to
Group 3 (placebo). Randomization of additional participants will be paused until a blinded 48-
hour sentinel safety evaluation of these 5 sentinel participants is completed. In the absence of any
clinically significant findings, upon decision by PI(s) and SRP, an additional 12 participants will
be randomized (5 additional participants in Groups 1 and 2 and 2 additional participants in Group 3
[placebo]). DRC will review blinded safety data of the initial 17 participants 7 days after the first
vaccination. DRC review will be held to review available safety data of initial participants enrolled
before these participants can receive the second vaccination. Further randomization in Cohort 1

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will be paused until the DRC safety evaluation is completed. In the absence of findings from the
DRC following the first vaccination, the remaining 43 participants in Cohort 1 will be randomized
and randomization in Cohort 2 may be initiated.
In Cohort 2, a total of 110 participants will be enrolled in a staggered approach(Figure 2). Initially,
5 sentinel participants will be randomized; 1 participant in each of the 5 groups (Groups 4 to 8
[including 1 placebo]). Randomization of additional participants will be paused until a blinded 48-
hour sentinel safety evaluation of these 5 sentinel participants is completed. In the absence of any
clinically significant findings, upon decision by PI(s) and SRP, an additional 10 participants will
be randomized in parallel (2 additional participants in Groups 4 to 8 [including 2 placebo]). DRC
will review blinded safety data of the 15 participants in Cohort 2, 7 days after the first vaccination.
DRC review will be held to review available safety data of initial participants enrolled before these
participants can receive the second vaccination. Further randomization in Cohort 2 will be paused
until the DRC safety evaluation is completed. In the absence of findings from the DRC following
the first vaccination, the remaining 95 participants in Cohort 2 will be randomized.
Refer to Section 4.1, Overall Design and Figure 2.
Blinding
The investigator will not be provided with randomization codes. The codes will be maintained
within the IWRS, which has the functionality to allow the investigator to break the blind for an
individual participant.
Data that may potentially unblind the intervention  assignment (ie, immunogenicity data, study
vaccine accountability data, study vaccine allocation, biomarker or other specific laboratory data)
will be handled with special care to ensure that the integrity of the blind is maintained and the
potential for bias is minimized. This can include making special provisions, such as segregating
the data in question from view by the investigators, clinical team, or others as appropriate until the
time of database lock and unblinding.
The participants, study-site personnel (including vaccine administrator) and investigator will be
blinded to study vaccine allocation throughout the study, except for the pharmacist or qualified
staff member with primary responsibility for study vaccine preparation and dispensing.
At the time of the primary analysis, the study will be unblinded for sponsor and external
partnerships personnel. Participants, clinical staff and study-site personnel will remain blinded to
the study vaccine allocation until the end of the study.
The investigator may in an emergency determine the identity of the intervention. While the
responsibility to break the intervention  code in emergency situations resides solely with the
investigator, it is recommended that the investigator contact the sponsor or its designee if possible
to discuss the particular situation, before breaking the blind. Telephone contact with the sponsor
or its designee will be available 24 hours per day, 7 days per week. In the event the blind is broken,
the sponsor must be informed as soon as possible. The date, time, and reason for the unblinding

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must be documented by the IWRS, in the appropriate section of the eCRF, and in the source
document.
Participants who have had their study vaccine assignment unblinded should continue to return for
scheduled evaluations.
In general, the randomization list will be disclosed fully only if the study is completed and the
clinical database is closed. However, if an interim analysis is specified, the randomization codes
and, if required, the translation of randomization codes into study vaccine and placebo groups will
be disclosed to those authorized and only for those participants included in the interim analysis.
In rare circumstances when a potential safety issue that may impact the overall benefit-risk
assessment of the investigational product has been identified in this study, selected sponsor
personnel may be unblinded to safety-related data in order to investigate the safety issue and
determine if additional actions are required. The safety data should be kept blinded to any
personnel not essential to the safety review.
If other rare, unforeseen circumstances arise that may necessitate unblinding of selected sponsor
personnel, these will be assessed and documented on a case-by-case basis. The data should be kept
blinded to any personnel not essential to the review or investigation.
6.4. 
Study Vaccine Compliance
Study vaccines will be administered intramuscularly by blinded qualified study-site personnel at
the study site. Details of each administration will be recorded in the eCRF (including date and time
of injection and location used for injection). For blinding procedures, see Section 6.3, Measures to
Minimize Bias: Randomization and Blinding.
6.5. 
Concomitant Therapy
Prestudy specific therapies such as analgesic/antipyretic medications and non-steroidal
anti-inflammatory drugs, or antihistamines administered up to 30 days before first dose of study
vaccine must be recorded at screening.
Any vaccination within 6 months before screening must be recorded at screening. Seasonal
influenza vaccination administered during the previous season (and, if possible, during the past 5
seasons) will be recorded at screening, if available.
Concomitant therapies such as analgesic/antipyretic medications and non-steroidal
anti-inflammatory drugs, or antihistamines must be recorded until 28 days after administration of
study vaccine and thereafter, pre-dose on the day of vaccination and for 28 days after each
subsequent dose of study vaccine. Any vaccination must be recorded until the end of the study.
All other concomitant therapies should also be recorded if administered in conjunction with new
or worsening AEs reported per-protocol requirements outlined in Section 8.3.1, Time Period and
Frequency for Collecting Adverse Event and Serious Adverse Event Information.

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Refer to Section 5.2, Exclusion Criteria for details on which medication is disallowed before study
drug administration and during the study. If any of these medications are indicated in a disease or
a post-exposure setting, these must take priority over the study intervention.
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in
which prohibited therapies are administered. Any use of disallowed medication is to be recorded
in the CRF.
6.6. 
Dose Modification
Dose modification is not applicable in this study.
6.7. 
Intervention After the End of the Study
There will be no study intervention following the end of the study.
6.8. 
Study Pausing Rules
If a study vaccination is considered to raise significant safety concerns (and a specific set of
pausing criteria have been met), further vaccination of participants may be paused after medical
review as described below. The concerned data will then be reviewed by the DRC, after which the
DRC will recommend whether the pause can be lifted or not, or whether other steps are needed.
1. The occurrence of any of the following events maylead to a pause in further study vaccination.
This list is only applicable for concerned AEs that occur up to 4 weeks after each vaccination
and for concerned SAEs from the first vaccination throughout the study. Death of a
participant, considered related to study vaccine or if the causal relationship to the study
vaccine cannot be excluded; OR
Note: All cases of death will be sent for DRC information. Upon their review, DRC may then
decide whether a study pause is required.
2. One or more participants experience an SAE, a Grade 4 (solicited or unsolicited) AE, or a
persistent (upon repeat testing) Grade 4 laboratory abnormalitythat is determined to be related
to study vaccine; OR
3. One or more participants experience anaphylaxis or generalized urticaria within 24 hours of
vaccination, clearly not attributable to other causes than vaccination with study vaccine; OR
4. Three or more participants experience a Grade 3 unsolicited AE of the same type (as per
medical judgment of the sponsor), that is determined to be related to study vaccine, that
persists for 72 hours or longer; OR one participant from sentinel cohort experiences a Grade
3 unsolicited AE that is determined to be related to study vaccine; OR
5. Three or more participants experience a persistent (upon repeat testing) Grade 3 laboratory
abnormality related to the same laboratory parameter and considered related to study vaccine;
OR One participant from sentinel cohort experiences a persistent (upon retesting) Grade 3
laboratory abnormality that is determined to be related to study vaccine; OR
6. Three or more participants experience a Grade 3 solicited AE of the same type, determined to
be related to study vaccine, and persisting as Grade 3 for longer than 3 consecutive days (ie,

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the day of occurrence of the AE is counted as Day 1); OR one participant from sentinel cohort
experiences a Grade 3 solicited systemic AE that is determined to be related to study vaccine.
For number 2 and number 5: to assess abnormal laboratory values, the test must be repeated at
least once, within 48 hours of the site becoming aware of the abnormal value.
For number 4, number 5 and number 6: after each DRC review of similar AEs, the Committee will
indicate the conditions under which it requires further notification and review of the subsequent
similar AEs.
To enable prompt response to a situation that could trigger pausing rules, the investigator should
notify the sponsor’s medical officer or designee (AND transmit SAE form [if applicable] in a
secure manner electronically or by facsimile [fax] to the sponsor), immediately and no later than
24 hours after becoming aware of any related AE of Grade 3 or above AND update the eCRF with
relevant information on the same day the AE information is collected. A thorough analysis of all
Grade 3 (or above) cases will be carried out by the sponsor’s medical officer or designee,
irrespective of whether the criteria for pausing the study are met. Based on the pausing criteria, the
sponsor’s medical officer or designee then decides whether a study pause is warranted. All sites
will be notified immediately in case of a study pause. The sponsor’s medical officer or designee is
responsible for the immediate notification of DRC members and coordination of a DRC meeting
in case of a study pause.
Vaccinations for an individual participant may be suspended for safety concerns other than those
described in the pausing criteria, at the discretion of the investigator if he/she feels the participant’s
safety may be threatened. The sponsor’s medical officer or designee or the investigator(s) (upon
consultation with the sponsor’s medical officer or designee) may initiate DRC review for any
single event or combination of multiple events which, in their professional opinion, could
jeopardize the safety of the participants or the reliability of the data.
Vaccinations for the study may be suspended for safety concerns other than those described above,
or before pausing rules are met, if, in the judgment of the DRC, participant safety may be
threatened.
Resumption of vaccinations will start only upon receipt of written recommendations by the DRC.
The clinical site(s) will be allowed to resume activities upon receipt of a written notification from
the sponsor. The communications from the DRC  will be forwarded by the investigator to the
Institutional Review Board/Independent Ethics Committee (IRB/IEC) and by the sponsor to the
relevant health authorities, according to local standards and regulations.
7. 
DISCONTINUATION OF STUDY VACCINE AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL
7.1. 
Discontinuation of Study Vaccine
Study vaccine administration will be withheld for the reasons listed below. These participants
should not receive any further doses of study vaccine but should remain on study for follow-up
with assessments of safety and immunogenicity, unless the participant withdraws consent for study

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participation. Additional unscheduled visits or telephone calls may be performed for
safety/reactogenicity reasons, if needed. In case of questions, the investigator is encouraged to
contact the sponsor.
 
Any related AE, worsening of health status or intercurrent illnesses that, in the opinion of the
investigator, requires discontinuation from study vaccine
 
The participant becomes pregnant
 
Unblinding on the participant level that, in the opinion of the sponsor, would compromise the
integrity of the data
 
Anaphylactic reaction and/or severe hypersensitivity reactionfollowing study vaccination, not
attributable to causes other than vaccination
 
SAE or potentially life-threatening (Grade 4) event that is determined to be related to study
vaccine
 
Chronic or recurrent use of immunomodulators/suppressors, eg, cancer chemotherapeutic
agents or systemic corticosteroids (see Section 5.2, Exclusion Criteria)
 
The investigator believes that for safety reasons or reactogenicity reasons (eg, AE) it is in the
best interest of the participant to discontinue study vaccination
 
The participant withdraws consent to receive further vaccination
7.1.1. 
Criteria for Temporarily Delaying Study Vaccine Administration
The following events constitute a temporary contraindication to study vaccination:
 
Clinically significant acute illness at the time of vaccination. This does not include minor
illnesses, such as diarrhea or mild upper respiratory tract infection.
 
Fever (body temperature ≥38.0°C  [100.4°F]) within 24 hours prior to the planned time of
vaccination.
 
Medically indicated vaccinations, including SARS-CoV-2 vaccine boosters.
 
An illness which in the judgement of the investigator may interfere with reactogenicity/Day 1-
8 safety assessments after each vaccination.
If any of these events occur at the scheduled time for the first vaccination, randomization at a later
date within the screening window is permitted at the discretion of the investigator and after
consultation with the sponsor. If randomization cannot occur within the screening window,
rescreening is required. If any of these events occur at the scheduled time for one of the subsequent
vaccinations, the vaccination can be rescheduled, as long as this is in agreement with the allowed
windows (see Visit Windows in Section 8, Study Assessments and Procedures).
Vaccination may be delayed for reasons other than acute illness at investigator’s discretion.
Vaccination must be completed within the specified window and upon approval of the sponsor. A
check of eligibility criteria may be repeated as necessary.

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If the vaccination visit cannot be rescheduled within the allowed window or the contraindications
to vaccination persist, the sponsor should be contacted for further guidance.
7.2. 
Participant Discontinuation/Withdrawal From the Study
A participant will be withdrawn from the study for any of the following reasons:
 
Lost to follow-up
 
Withdrawal of consent for study participation
 
Death
 
Any AE that requires discontinuation from the study
 
Repeated failure to comply with protocol requirements
 
Decision by the sponsor or the investigator to stop or cancel the study
 
Decision by local regulatory authorities or IRB/IEC to stop or cancel the study
When a participant withdraws before study  completion, the reason for withdrawal is to be
documented in the eCRF and in the source document. Participants who wish to withdraw consent
from participation in the study will be offered a single exit visit for safety follow-up (prior to
formal withdrawal of consent). They have the right to refuse.
Withdrawal of Consent
A participant declining to return for scheduled visits does not necessarily constitute withdrawal of
consent. Alternate follow-up mechanisms that the participant agreed to when signing the consent
form apply as local regulations permit.
7.2.1. 
Withdrawal From the Use of Research Samples
Withdrawal From the Use of Samples in Future Research
The participant may withdraw consent for use of samples for research (refer to Long-Term
Retention of Samples for Additional Future Research in in Section 10.3, Appendix 3, Regulatory,
Ethical, and Study Oversight Considerations). In such a case, samples will be destroyed after they
are no longer needed for the clinical study. Details of the sample retention for research are
presented in the main ICF.
7.3. 
Lost to Follow-up
A participant will be considered lost to follow-up if the participant repeatedly fails to return for
scheduled visits and is unable to be contacted by the study site. A participant cannot be deemed
lost to follow-up until all reasonable efforts made by the study-site personnel to contact the
participant are deemed futile. The following actions must be taken if a participant fails to return to
the study site for a required study visit:
 
The study-site personnel must attempt to contact the participant to reschedule the missed visit
as soon as possible, to counsel the participant on the importance of maintaining the assigned
visit schedule, to ascertain whether the participant wishes to or should continue in the study.

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 
Before a participant is deemed lost to follow-up, the investigator or designee must make every
reasonable effort to regain contact with the participant (where possible, 3 telephone calls, e-
mails, fax, and, if necessary, a certified letter to the participant’s last known mailing address,
or local equivalent methods). Locator agencies may also be used as local regulations permit.
These contact attempts should be documented in the participant’s medical records.
 
Should the participant continue to be unreachable, they will be considered to have withdrawn
from the study.
Should a study site close, eg, for operational, financial, or other reasons, and the investigator cannot
reach the participant to inform them, their contact information will be transferred to another study
site as permitted by local regulations.
7.4. 
Staggered Vaccination
The investigator is not permitted to start vaccinating additional study participants in Cohort 1 or
progress to Cohort 2 until receipt of favorable written documentation of DRC safety evaluations
(see Section 4.1, Overall Design and Figure 2).
Screening procedures may continue to facilitate enrollment of remaining participants.
8. 
STUDY ASSESSMENTS AND PROCEDURES
Overview
Section 1.3, Schedule of Activities summarizes the frequency and timing of safety  and
immunogenicity measurements applicable to this study. Additionally, a summary of assessments
for participants with  ILI is provided showing procedures applicable for the participant and the
study site. See Section 1.3.2, Schedule of Activities –Assessments for Participants With Influenza-
like Illness (ILI).
If multiple assessments are scheduled for the same timepoint, it is recommended that procedures
be performed in the following sequence: physical examination and vital signs before blood draws
and nasal swab sample collection. If needed, assessments may be performed at another day within
the applicable visit window. Actual dates and times of assessments will be recorded in the source
document and in the eCRF.
Additional serum or urine pregnancy tests may be performed, as determined necessary by the
investigator or required by local regulation, to establish  the absence of pregnancy at any time
during the participation in the study.
Participants will be provided with a thermometer (to measure body temperature), ruler (to measure
injection site reactions), and participant diary to record body temperature and solicited injection
site and systemic signs and symptoms.
The diary includes instructions on how to capture the data and grading scales to assess severity of
the signs and symptoms. The site staff is responsible for providing appropriate training to the
participant to avoid missing or incorrect data. The diary will be reviewed by the study personnel

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at visits indicated in Section 1.3, Schedule of Activities. If the diary review is missed, the diary
will be reviewed during the following visit. If a participant misses a vaccination, the diary covering
the period after the missed vaccination does not have to be filled in.
Participants will be provided with a Flu-iiQTM  questionnaire and ILI form to record signs and
symptoms of influenza during the influenza season. See Section 8.1.1, ILI Procedures.
The total blood volume to be collected from each participant will be approximately 219 mL. The
maximum volume of blood to be drawn at any given visit will be approximately 41.5 mL.
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the
samples.
Visit Windows
Visit windows will be allowed as indicated in Table 2.
The timings of the post-vaccination visits will be determined relative to the actual day of the
corresponding vaccination. If a participant misses a vaccination, the post-vaccination visits will be
calculated from the imputative vaccination date according to protocol.
Table 2: 
Visit Windows
VISIT  
Visit Day  
Window  
Primary Purpose
Visit 1 
Day -42 to 1 
– 
Screening visit
Visit 2 
Day 1 
– 
FIRST STUDY VACCINATION
Visit 3 
Day 8 
(Vac 1+7 days) 
+2 days 
7-day post-first study vaccination safety and
immunogenicity visit a
Visit 4 
Day 29 
(Vac 1+28 days) 
±3 days 
28-day post-first study vaccination safety and
immunogenicity visit
Visit 5 
Day 57 
±3 days 
SECOND STUDY VACCINATION
Visit 6 
Day 64 
(Vac 2+7 days) 
+2 days 
7-day post-second study vaccination safety and
immunogenicity visit a
Visit 7 
Day 85 
(Vac 2+28 days) 
±3 days 
28-day post-second study vaccination safety and
immunogenicity visit
Visit 8 
Day 238 
(Vac 2+6 months) 
±14 days 
6-month post-second study vaccination safety and
immunogenicity visit
Visit 9 
Day 365 
(Vac 1+12 months) 
±30 days 
FINAL VISIT: 12-month post-first study vaccination
safety and immunogenicity visit
a 
Sentinel participants will additionally be contacted by telephone 48 hours post-vaccination to collect safety
information.

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Screening
Screening may be conducted in part via a sponsor- and IRB/IEC-pre-approved non-study specific
screening consent process, but only if the relevant pre-screening tests are identical to the
per-protocol screening tests and are within 6 weeks prior to first vaccination. However, no study-
specific procedures, other than these pre-approved pre-screening assessments, will be performed
until the participant has signed the study-specific ICF. The study specific ICF date will be entered
into the eCRF. The non-study specific ICF will be considered source data.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the eCRF or laboratory
requisition form.
Refer to Section 1.3, Schedule of Activities for the timing and frequency of all sample collections.
Instructions for the collection, handling, storage, and shipment of samples are found in  the
laboratory manual that will be provided, or per the requirements of local laboratories. Collection,
handling, storage, and shipment of samples must be under the specified, and where applicable,
controlled temperature conditions as indicated in the laboratory manual, or per the requirements
of local laboratories.
Study-Specific Materials
The investigator will be provided with the following materials:
 
IB for Uniflu Vaccine
 
Thermometer
 
Ruler (to measure diameter of any erythema and swelling)
 
Pharmacy manual/study SIPPM
 
Laboratory manual
 
IWRS Manual
 
Electronic Data Capture (eDC) Manual/ eCRF completion guidelines
 
Sample ICF
 
Participant diaries
 
Flu-iiQTM questionnaire
 
ILI form to document body temperature, concomitant medication used, etc.
 
Nasal swab kits and instructions
 
Insulated cooler bag (for participants to transfer nasal swab samples collected at home to sites
at defined temperature for ILI events)
 
Contact information page(s)

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8.1. 
Immunogenicity Assessments
Immunogenicity assessments may include, but are not limited to, the immunogenicity assays (as
available and applicable) summarized in Table 3. Timings of blood draws are specified in
Section 1.3, Schedule of Activities.
Immunogenicity assessments supporting the secondary endpoint were chosen to quantify the
magnitude of the pre-existing influenza-specific immunity and vaccine-induced antibody
responses that are thought to contribute to the protective capacity of HA stem-based vaccination
approaches. Antibodies targeting the stem domain of the influenza HA molecule will be quantified
by ELISA using full-length HA or stem-only antigens that are expected to sensitively and
specifically detect responses targeting the conserved stem domain of the molecule.
Immunogenicity assessments supporting the exploratory endpoint were chosen to further quantify
the magnitude and characterize pre-existing influenza-specific immunity and vaccine-induced
immune responses. This characterization entails a deeper investigation of the breadth and
functionality of the antibody response, the set-up of assays and characterization of mucosal
targeting of the immune response, and characterization of cellular and molecular effects of
vaccination.
Although this study is not designed to support the identification or validation of surrogates of
protection against clinically manifest influenza infection, immunological assessments supporting
the secondary and exploratory endpoints will be evaluated for their utility as potential surrogates
of protection, to be applied to and further characterized in follow-up studies, such as challenge
studies or Phase 2b proof-of-concept studies.
Blood for humoral immune responses will be drawn from all participants. Influenza immunity in
study participants will be determined on baseline (Day 1) and post-vaccination blood samples as
described in Section 1.3, Schedule of Activities. Both assay variability and pre-existing immunity
will be taken into consideration in the immunogenicity assessments.
PaxGene tubes and proteome stabilization samples will be collected according to Section 1.3,
Schedule of Activities. PaxGene samples will allow the performance of whole blood transcript
profiling.
Nasosorption samples (using SAM), collected at the timepoints indicated in Section 1.3, Schedule
of Activities, will be used for the development of mucosal influenza-specific IgG and/or IgA
ELISAs and the assessment of those responses in nasal secretions.
In addition to RT-PCR based diagnosis of influenza virus infection performed on nasal swab
samples (collected when ILI symptoms develop during the influenza season), blood samples
collected at baseline, between 2 and 4 days after symptom onset (ILI Days 3-5), and at 28 days
after symptom onset (ILI Day 29) from participants with a suspected ILI will also be assayed by
serology (including but not limited to HAI assay as available and applicable) for influenza virus

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exposure confirmation. Additionally, the nasal swab samples might be used to determine the
presence of other respiratory pathogens.
Sample collection and processing will be performed by the staff at the clinical site according to
current versions of approved standard operating procedures.
Samples collected for immunogenicity analyses may additionally be used to evaluate safety and
serology (HAI) that address concerns arising during or after the study period. Participant
confidentiality will be maintained.
Table 3: 
Summary of Immunogenicity Assays
Endpoint 
Assay
Secondary endpoints
Quantification of antibody binding 
to HA stem or full-length HA
ELISA
Exploratory endpoints
Neutralization  
Virus neutralization assay
Fc-mediated functionality  
Human FcγRIIIa reporter assay
Breadth of the antibody response 
within Group 1 or beyond
ELISA using full-length HAs indicative of clade or group coverage
HA stem- or epitope-specificity  
ELISAs using HA stem protein or competition ELISAs using bnAbs or
HA proteins
Functional breadth of the antibody 
response within Group 1 or beyond 
Virus neutralization assays or serum transfer into animal challenge
models
Functional characterization of the 
antibody response 
Assays assessing Fc-mediated functions (eg, antibody-dependent
cytotoxicity assay, or antibody-dependent cellular phagocytosis assay),
HA conformational change assays, or other assays
Molecular characterization of the 
antibody response 
Assays assessing the epitope-specificity, glycosylation status, or other
characteristics of the antibody (eg, systems serology arrays)
Innate immune responses 
Transcript- or cytokine profiling
Gene expression profiles 
RNA sequencing or other transcriptional profiling methods, including,
but not limited to TCR or BCR repertoire analysis
Nasal antibody response 
IgG and/or IgA ELISA in nasal secretions
Hemagglutination inhibition 
HAI assays
BCR = B cell receptor; bnAbs = broadly neutralizing antibodies; ELISA = enzyme-linked immunosorbent assay; Fc = fragment
crystallizable; HA = hemagglutinin; HAI = hemagglutination inhibition; Ig = immunoglobulin; RNA = ribonucleic acid; TCR = T
cell receptor.
8.1.1. 
ILI Procedures
Participants will be informed of the timing of the start and end of the influenza season in
accordance with the country/region-specific influenza local surveillance system.
For the duration of the influenza season, participants will be followed-up to identify potential cases
of influenza virus infection. During the influenza season, participants should record any signs and
symptoms of ILI (such as cough, sore throat, headache, nasal congestion, feeling feverish, body

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aches and pains, fatigue, or neck pain), including measurement ofbody temperature a, on a daily
basis until symptoms have resolved using a specific Flu-iiQTM questionnaire andan ILI form. Signs
and symptoms of ILI recorded on the Flu-iiQTM  questionnaire and ILI form will be transferred
onto the ILI symptoms page in the eCRF. The Flu-iiQTM questionnaire and ILI form will be the
primary sourcefor ILI monitoring. Participants should complete a new questionnaire on each day
they experience symptoms, including the day on which the symptoms resolve. Completed ILI
questionnaires can either be mailed to the site or brought to the site at the next visit.
If ILI symptoms develop during the influenza season, the following should take place:
 
Participants should contact the site as soon as possible to notify the site of ILI.
 
Participants should record signs and symptoms of the ILI daily using the Flu-iiQTM
questionnaire from onset of symptoms until the day of symptom resolution, and record body
temperature daily using an ILI form provided by the sponsor until the day of symptom
resolution.
 
Participants should take a nasal sample at home on the day of symptom onset or the day
thereafter (ILI Days 1-2). The sample should be stored refrigerated and brought to the site by
the participant within 4 days (preferably) after collection.
 
Participants should go to their study site, ideally between 2 and 4 days after symptom onset
(ILI Days 3-5), where
 
the completed Flu-iiQTM  questionnaire and ILI form will be collected and reviewed by
site staff;
 
the participant nasal self-swab sample (taken on ILI Days 1-2) will be collected;
 
an additional nasal swab will be taken by a qualified member of the site staff;
 
the presence of influenza virus infection will be assessed by qualified site staff by RT-
PCR diagnostics and/or rapid-PCR detection (eg, by Cepheid GeneXpert®) on the nasal
swab samples mentioned above;
 
a blood sample for seroconfirmation of influenza virus infection  will be taken by a
qualified member of the site staff;
 
and vital signs, including body temperature, blood pressure, heart rate, respiratory rate
and oxygen saturation, will be measured by a qualified member of the site staff. A clinical
assessment, including a targeted physical examination, will be completed by qualified
site staff, preferably by a physician, physician assistant, nurse practitioner, or equivalent.b
 
At ILI Day 29 (±7 days), participants will be asked to return to the site where
a 
Oral temperature should be measured at approximately the same time each day, preferably in the evening, using
the thermometer supplied.
b 
It is recommended that vital signs are measured before collection of nasal swabs and blood draws.

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 
the completed Flu-iiQTM  questionnaire and ILI form will be collected and reviewed by
site staff;
 
a blood sample for seroconfirmation of influenza virus infection will be taken  by a
qualified member of the site staff;
 
and vital signs, including body temperature, blood pressure, heart rate, respiratory rate
and oxygen saturation will be measured by a qualified member of the site staff. A clinical
assessment (including a targeted physical examination) will be performed by qualified
site staff, preferably by a physician, physician assistant, nurse practitioner, or equivalent.a
 
For all medically attended ILIs, including those resulting in hospitalization, additional
information on any other diagnostics (eg, chest x-rays, spirometry, pulmonary function tests)
or interventions during the clinical course of ILI will be collected.
The Flu-iiQTM  questionnaire, ILI form and nasal swab kits for use at home will be distributed
before the start of the influenza season, along with an insulated cooler bag for participants to
transfer nasal swab samples collected at home to sites at defined temperature.
During the influenza season, participants will be contacted by telephone or other means of
communication approximately every 14±3 days (unless a planned visit has occurred or will occur
within 14 days). These calls will remind participants to complete the Flu-iiQTM questionnaire and
ILI form in the event of any symptoms of ILI, and to contact the site and to take a nasal sample at
the time of symptom onset. These calls will also check for any SAEs, and associated concomitant
medications since the previous visit or telephone contact.
The presence of influenza virus will be assessed by qualified site staffby RT-PCR diagnostics on
the nasal swab samples, which may include viral load and influenza subtyping. In addition, blood
samples from participants with a suspected ILI will also be assayed by serology by the sponsor
(including but not limited to HAI assay as available and applicable) for influenza virus exposure
confirmation. The blood samples may additionally be used to evaluate immune responses during
the ILI.
Every effort should be made to collect data on the clinical course of ILIs including information on
hospitalization, oxygenation status, supplemental oxygen requirements and specific drug
treatments, as well as other concurrent respiratory illness present at the time of the diagnosis of
the event and up to symptom resolution.
For participants who experience symptoms suggesting ILI, RT-PCR assay of the nasal swabs taken
after symptom onset will be used to determine whether the infection was caused by influenza virus.
For participants hospitalized with symptoms of ILI, confirmation of influenza virus infection using
RT-PCR may be performed at the local (hospital) laboratory.
a 
It is recommended that vital signs are measured before collection of nasal swabs and blood draws.

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Any ILI and complications related to ILIs will be reported as an AE if it occurs between the time
of any vaccination through the following 28 days. An ILI and complications related to ILIs that
occur outside of this period during influenza season does not require AE reporting unless ongoing
at the time of subsequent vaccination. Any ILI and complications related to ILIs fulfilling the
criteria of an SAE will be reported as such during the entire studyperiod from the first vaccination.
8.2. 
Safety Assessments
On a daily basis, for 7 days after each vaccination, participants will be asked to record symptoms
of the following AEs via the participant diary:
 
Solicited injection site AEs: erythema (measured using the ruler supplied), swelling (measured
using the ruler supplied), and pain/tenderness.
 
Solicited systemic AEs: fatigue, headache, myalgia, nausea and fever (ie, body temperature
≥38 °C [100.4°F]).
Oral temperature should be measured at approximately the same time each day, preferably in the
evening, using the thermometer supplied. Temperature 7 days after each vaccination may be
collected earlier on the Day 8 or Day 64 to coincide with the clinic visit.
Participants will record signs and symptoms of ILI during the influenza season using the Flu-iiQTM
questionnaire and ILI form: signs and symptoms of ILI will be collected on the Influenza
Symptoms page in the eCRF; influenza infections, preferably as a diagnosis, will also be reported
on the AE page of the eCRF if they occur within 28 days following vaccination.
Adverse events will be reported and followed by the investigator as specified in Section 8.3,
Adverse Events, Serious Adverse Events, and Other Safety Reporting and Section  10.4,
Appendix 4, Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-Up,
and Reporting.
Any clinically relevant changes occurring during the study must be recorded on the Adverse Event
section of the eCRF.
Any clinically significant abnormalities persisting at the end of the study/early withdrawal will be
followed by the investigator until resolution or until a clinically stable condition is reached.
The study will include the following evaluations of safety and reactogenicity according to the time
points provided in Section 1.3, Schedule of Activities.
8.2.1. 
Physical Examinations
A full physical examination, including height and body weight, will be carried out at screening, as
specified in Section 1.3, Schedule of Activities. Weight will be measured lightly clothed and
without footwear, and height will be measured without footwear. At all other study visits, an
abbreviated, symptom-directed examination will be performed based on clinically relevant issues,
clinically relevant symptoms, and medical history if determined necessary by the investigator. A
symptom-directed physical examination may be repeated if deemed necessary by the investigator.

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Physical examinations will be performed by the investigator or by a designated medically trained
clinician. Any clinically relevant abnormalities or changes in severity observed during the review
of body systems should be documented in the eCRF as an AE or SAE if it meets the criteria for an
AE or SAE according to the protocol reporting requirements (see Section 8.3.1, Time Period and
Frequency for Collecting Adverse Event and Serious Adverse Event Information). Any
abnormalities or changes in severity that occurred after signing of the ICF until immediately before
vaccination would be recorded if due to participation in the study.
8.2.2. 
Vital Signs
Vital Signs will be examined as specified in Section 1.3, Schedule of Activities. Temperature (oral
route preferred, or in accordance with the local standard of care), pulse/heart rate, respiratory rate,
and blood pressure will be assessed.
Participants will utilize a diary to document the body temperature reading.
Blood pressure and pulse/heart rate measurements will be assessed (supine) with a completely
automated device. Manual techniques will be used only if an automated device is not available.
Blood pressure and pulse/heart rate measurements should be preceded by at least 5 minutes of rest
in a quiet setting without distractions (eg, television, cell phones).
8.2.3. 
Clinical Safety Laboratory Assessments
Blood samples for clinical laboratory assessments will be collected as indicated in Section 1.3
Schedule of Activities and Section 10.6, Appendix 6: Clinical Laboratory Tests. The investigator
must review the laboratory results, document this review, and record any clinically relevant
changes occurring during the study in the AE section of the eCRF. The laboratory reports must be
filed with the source documents.
8.2.4. 
Pregnancy Testing
A negative serum pregnancy test for female participants of childbearing potential must be obtained
at screening visit. A negative urine pregnancy test for female participants of childbearing potential
must be obtained before the first dose of study vaccine on Day 1 and the second dose of study
vaccine on Day 57.
Additional serum or urine pregnancy tests may be performed, as determined necessary by the
investigator or required by local regulation, to establish the absence of pregnancy at any time
during the participation in the study.
8.3. 
Adverse Events, Serious Adverse Events, and Other Safety Reporting
Timely, accurate, and complete reporting and analysis of safety information from clinical studies
are crucial for the protection of participants, investigators, and the sponsor, and are mandated by
regulatory agencies worldwide. The sponsor has established standard operating procedures in
conformity with regulatory requirements worldwide to ensure appropriate reporting of safety

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information; all clinical studies conducted by the sponsor or its affiliates will be conducted in
accordance with those procedures.
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, surrogate,
or the participant's legally acceptable representative) for the duration of the study.
For further details on AEs, SAEs, and product quality complaints (PQC), refer to Section 10.4,
Appendix 4, Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-Up,
and Reporting.
8.3.1. 
Time Period and Frequency for Collecting Adverse Event and Serious
Adverse Event Information
All Adverse Events
Adverse events and special reporting situations, whether serious or non-serious, that are related to
study procedures or that are related to non-investigational sponsor products will be reported from
the time a signed and dated ICF is obtained until the end of the study/early withdrawal.
Clinically relevant medical events not meeting the above criteria and occurring between signing
of ICF and date of first vaccination will be collected on the Medical History eCRF page as
pre-existing conditions.
Solicited AEs, collected through a diary, will be recorded for each vaccination from the moment
of vaccination until 7 days post-vaccination.
All other unsolicited AEs and special reporting situations, whether serious or non-serious, will be
collected for each vaccination from the moment of vaccination until 28 days post-vaccination.
Unsolicited AEs with the onset date outside the timeframe defined above (>28 days after previous
study vaccination), which are ongoing on the day of the subsequent vaccination, should be
recorded on the eCRF AE page.
All SAEs and AEs leading to discontinuation from further study vaccination (regardless of the
causal relationship) are to be reported from the moment of first vaccination until completion of the
participant’s last study-related procedure, which may include contact for safety follow-up. The
sponsor will evaluate any safety information that is spontaneously reported by an investigator
beyond the time frame specified in the protocol.
AEs of Grade 3 or Above that are Related to Study Vaccine
All AEs of Grade 3 or above that are related to study vaccine must be reported to the appropriate
sponsor contact person by study-site personnel immediately, but no later than 24 hours of their
knowledge of the events. Relevant AE information should be updated in the eCRF on the same
day when the AE information is collected (see Section 6.8 Study Pausing Rules).

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Serious Adverse Events
All SAEs occurring during the study must be reported to the appropriate sponsor contact person
by study-site personnel immediately, but no later than 24 hours of their knowledge of the event.
Information regarding SAEs will be transmitted to the sponsor using the Serious Adverse Event
Form, which must be completed and signed by a physician from the study site, and transmitted to
the sponsor immediately, but no later than 24 hours of their knowledge of the event. The initial
and follow-up reports of an SAE should be transmitted in a secure manner electronically or by
facsimile (fax). Telephone reporting should be the exception and the reporter should be asked to
complete the appropriate form(s) first.
8.3.2. 
Method of Detecting Adverse Events and Serious Adverse Events
Care will be taken not to introduce bias when detecting AEs or SAEs. Open-ended and nonleading
verbal questioning of the participant is the preferred method to inquire about AE occurrence.
Solicited Adverse Events
Solicited AEs are used to assess the reactogenicity of the study vaccine and are predefined local
(at the injection site) and systemic events for which the participant is specifically questioned and
which are noted by participants in their diary.
After each vaccination, participants will remain under observation at the study site for at least
30 minutes for presence of any acute reactions and solicited events. In addition, participants will
record solicited signs and symptoms in a diary for 7 days post-vaccination. All participants will be
provided with a diary and instructions on how to complete the diary (see Overview in Section 8,
Study Assessments and Procedures). The site staff will verbatim transcribe the information
provided by the participant into the relevant sections of the eCRF. Review of diary entries with
participants and grading of symptoms must be done by a qualified and delegated site staff member
under the oversight of the investigator or a delegated physician. After review of the diary entries
with the participant, the investigator or qualified delegate, will complete their own assessment and
document it in the relevant sections of the eCRF. Once a solicited sign or symptom from a diary
is considered to be of severity Grade 1 or above, it will be recorded as a solicited AE.
Solicited Injection Site Adverse Events
Participants will be asked to note in the diary occurrences of injection site pain/tenderness,
erythema, and swelling at the study vaccine injection site daily for 7 days post-vaccination (day of
vaccination and the subsequent 7 days). The extent (largest diameter) of any erythema and swelling
should be measured (using the ruler supplied) and recorded daily. The case definitions for solicited
injection site events can be found in Section 11, References (Gidudu 2012; Kohl 2007).
Solicited Systemic Adverse Events
Participants will be instructed on how to record daily temperature using a thermometer provided
for home use. Participants should record the temperature in the diary in the evening of the day of
vaccination, and then daily for the next 7 days approximately at the same time each day. If more

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than one measurement is made on any given day, the highest temperature of that day will be used
in the eCRF.
Fever is defined as endogenous elevation of body temperature ≥38° C (100.4°F), as recorded in at
least one measurement (Marcy 2004).
Participants will also be instructed on how to note signs and symptoms in the diary on a daily basis
for 7 days post-vaccination (day of vaccination and the subsequent 7 days), for the following
events: fatigue, headache, nausea, and myalgia.
Unsolicited Adverse Events
Unsolicited AEs are all AEs for which the participant is not specifically questioned.
8.3.3. 
Follow-up of Adverse Events and Serious Adverse Events
The investigator is obligated to perform or arrange for the conduct of supplemental measurements
and evaluations as medically indicated to elucidate the nature and causality of the AE, SAE, or
PQC as fully as possible. This may include additional laboratory tests or investigations,
histopathological examinations, or consultation with other health care professionals.
Adverse events and the special reporting situation of pregnancy will be followed by the
investigator as specified in Section 10.4, Appendix 4, Adverse Events: Definitions and Procedures
for Recording, Evaluating, Follow-up, and Reporting.
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events
The sponsor assumes responsibility for appropriate reporting of AEs to the regulatory authorities.
The sponsor will also report to the investigator (and the head of the investigational institute where
required) all suspected unexpected serious adverse reactions (SUSARs). The investigator (or
sponsor where required) must report SUSARs to the appropriate IEC/IRB that approved the
protocol unless otherwise required and documented by the IEC/IRB. A SUSAR will be reported to
regulatory authorities unblinded. Participating investigators and IEC/IRB will receive a blinded
SUSAR summary, unless otherwise specified.
8.3.5. 
Pregnancy
All initial reports of pregnancy in female participants or partners of male participants must be
reported to the sponsor by the study-site personnel immediately, but no later than 24 hours of their
knowledge of the event using the appropriate pregnancy notification form. Abnormal pregnancy
outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic
pregnancy) are considered SAEs and must be reported using the Serious Adverse Event Form. Any
participant who becomes pregnant during the study must discontinue further study vaccine, but
remain on study for follow-up with assessments of safety and immunogenicity (see Section 7.1
Discontinuation of Study Vaccine).
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the
infant will be required.

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If the partner of a male participant becomes pregnant during the study, follow-up information
regarding the outcome of the pregnancy will be requestedupon the consent provided by the partner.
8.4. 
Treatment of Overdose
For this study, any dose of INFLUENZA G1 mHA  greater than  the assigned dose will be
considered an overdose. The sponsor does not recommend specific interventions for an overdose.
In the event of an overdose, the investigator should:
 
Contact the sponsor’s medical officer immediately.
 
Closely monitor the participant for AE/SAE (ie, the participant will remain at the study site
for at least 1 hour and will be closely monitored for allergic or other reaction by site staff. A
follow-up telephone call 12 hours and 24 hours post-dose will be made).
 
Document the quantity of the excess dose of the overdosing in the eCRF.
8.5. 
Medical Resource Utilization and Health Economics
Health Economics/Medical Resource Utilization and Health Economics parameters are not
evaluated in this study.
9. 
STATISTICAL CONSIDERATIONS
Statistical analysis will be done by the sponsor or under the authority of the sponsor. A general
description of the statistical methods to be used to analyze the immunogenicity and safety data is
outlined below. Specific details will be provided in the Statistical Analysis Plan (SAP).
9.1. 
Statistical Hypotheses
No formal statistical hypothesis for safety or immunogenicity will be tested.
9.2. 
Sample Size Determination
The study will evaluate whether INFLUENZA G1 mHA, with or without Al(OH)3 adjuvant, is
safe, well tolerated and immunogenic in healthy adults aged ≥18 to ≤45 years.
There are 170 participants planned to be randomized in this study.
With 25 participants in one vaccine regimen, the observation of no vaccine reactions after the first
vaccination would be associated with a 95% confidence that the true rate is less than 11.3%. Across
active regimens (N=150), the observation of 0 vaccine reactions after the first vaccination would
be associated with a 95% confidence that the true rate is less than 2.0%.
Table 4 below shows the probabilities of observing at least one AE in samples of different sizes at
given true AE rates. Placebo recipients will be shown pooled.

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Table 4: 
Probability of Observing at Least One Adverse Event at a Given True Adverse Event Rate
True 
Adverse
Probability of Observing at Least One Adverse Event in N Participants
Event Rate 
N=25 
N=50 
N=150
0.5% 
12%  
22% 
53%
1%  
22% 
39% 
78%
2% 
40%  
64%  
95%
5% 
72% 
92% 
100%
10%  
93% 
99% 
100%
25% 
100%  
100%  
100%
N = number of participants
This is the first study in humans and standard deviation of selected immunological assays is not
yet known in this population. Immunogenicity will be based on the estimation ofgeometric mean
titer (GMT) ratios at each timepoint versus baseline and their corresponding 95% confidence
intervals (CIs).
Assuming that approximately 12% of participants might be excluded from Per-protocol
Immunogenicity (PPI) due to dropout or major protocol deviation impacting immunogenicity, we
will have 22 participants per regimen. Table 5 below presents the power of the study to detect a
significant difference for several true ratios, assuming a range of standard deviations for ELISA
on the log10 scale (two-sided alpha = 0.05).
Table 5: 
Power to Detect a Significant Difference at a Given True Ratio
Fold Change (Difference on Log10 Scale)
Assumed Standard Deviation on Log10 Scale
0.181 
0.301 
0.421 
0.542 
0.643 
0.783
1 (diff. on log10=0) - no difference 
5.0% 
5.0% 
5.0% 
5.0% 
5.0% 
5.0%
1.5 (diff. on log10=0.176) 
88.5% 
47.4%  
27.3% 
18.4%  
14.4%  
11.3%
2 (diff. on log10=0.301) 
100.0%  
90.0%  
63.9% 
43.7% 
32.9% 
23.8%
3 (diff. on log10=0.477) 
100.0%  
100.0%  
95.6% 
81.4%  
67.2% 
50.6%
9.3. 
Populations for Analyses
For purposes of analysis, the following populations are defined:
Population 
Description
Full Analysis Set 
(FAS) 
The full analysis set will include all participants with at least one vaccination
documented.
All safety and participant information analyses will be based on the FAS.
Per-protocol 
Immunogenicity 
(PPI) 
The PPI population will include all randomized and vaccinated participants for
whom immunogenicity data are available excluding samples taken on or after the
date when a participant experiences a major protocol deviation expected to impact
the immunogenicity outcomes.
In addition, samples obtained after missed doses or samples obtained after natural
infection (if applicable) will be excluded from the analysis.
 
For participants who experience a natural influenza infection (based on RT-
PCR, or other sources), samples collected at and after the natural infection will
not be considered in the assessment of the immunogenicity of the selected
regimen.

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Population 
Description
 
If a participant misses one or more active dose(s) of the selected regimen but
continues the planned visit schedule, samples after the missed active dose(s)
will not be considered.
The analysis of all secondary and exploratory immunogenicity endpoints will be
based on the PPI set. Depending on the number of samples excluded, a post-hoc
exploratory analysis might be performed, including the excluded samples. To
visualize excluded samples, participant profiles from several assays might be
repeated, indicating the excluded samples.
Vaccine assignment will follow the as-treated principle.
9.4. 
Statistical Analyses
The SAP will be finalized prior to database lock for primary analyses (at the latest) and it will
include a more technical and detailed description of the statistical analyses described in this
section. This section is a summary of the planned statistical analyses of the most important
endpoints including primary and key secondary endpoints. A separate analysis plan will be created
to support DRC meetings and this document will be finalized prior to the data extraction for the
first DRC meeting to review 7-day safety data post-first study vaccination from Cohort 1
participants.
The safety and immunogenicity analysis will include the timepoints described in Section 1.3,
Schedule of Activities.
9.4.1. 
General Considerations
Analysis populations are defined in Section 9.3, Populations for Analyses.
Planned analyses are defined in Section 9.5, Planned Analyses.
9.4.2. 
Primary Endpoint(s)
Safety Endpoints
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively
per study  group, with special attention for SAEs, Grade 3/4 AEs, and AEs leading to
discontinuation of study vaccine. Safety will also be assessed throughout the study through routine
vital signs and physical examination as well as through clinical safety laboratory assessments. All
safety analyses will be made on the FAS.
Adverse Events
The verbatim terms used in the eCRF by investigators to identify AEs will be coded using the
Medical Dictionary for Regulatory Activities (MedDRA). All reported AEs will be included in the
analysis. For each AE, the percentage of participants who experience at least 1 occurrence of the
given event will be summarized by intervention group.

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Summaries, listings, datasets, or participant narratives may be provided, as appropriate, for those
participants who die, who discontinue intervention due to an AE, or who experience a severe AE
or an SAE.
Solicited injection site and systemic AEs will be summarized descriptively. The number and
percentages of participants with at least one solicited injection  site or systemic AE will be
presented. The overall frequencies per vaccine group as well as frequencies according to severity
and duration will be calculated for solicited AEs. Frequencies of unsolicited AEs, separately for
all and vaccination-related only, will be presented by System Organ Class and preferred term,
while those of solicited AEs will be presented only by preferred term.
9.4.3. 
Secondary Endpoint(s)
Immunogenicity Endpoints
No formal hypothesis on immunogenicity will be tested. Descriptive statistics (geometric mean
and 95% CI, or median and quartile range [Q1-Q3], as appropriate) will be calculated for
continuous immunological parameters at all time points and for changes from baseline. Graphical
representations of immunological parameters will be made as applicable. Frequency tabulations
will be calculated for discrete (qualitative) immunological parameters as applicable. The
immunogenicity analyses will be performed on the PPI set. An additional analysis might be done
for the FAS.
9.4.4. 
Tertiary/Exploratory Endpoint(s)
Detailed statistical methodology will be described in the SAP.
9.5. 
Planned Analyses
The primary analysis will occur when all participants have completed the 28 days post-Dose 2
visit or have discontinued earlier. These analyses will include immunogenicity  data on
quantification of antibody binding to full-length HA and HA stem protein and safety data up to the
28 days post-dose 2 visit. At the time of the primary analysis, the study will be unblinded for
sponsor and external partnerships personnel who are involved in the data analysis and decision
making. Participants and study-site personnel will remain blinded to the study vaccine allocation
until the end of the study.
An additional analysis will occur when all participants have completed the 6-month post-Dose 2
visit or discontinued earlier. These analyses will include additional safety data up to the 6 months
post-Dose 2 visit and immunogenicity data required per the sponsor’s assessment. This analysis
may allow to evaluate persistence of immune responses.
No study modifications are planned as a result of primary or additional analyses. The exact scope
of each analysis will be defined based on the availability of immunogenicity data and findings
from previous analyses. Additional interim analyses may be performed during the study for the
purpose of informing future vaccine development-related decisions in a timely manner, or upon
health authority request. If required, these unplanned interim analyses may replace or be combined
with planned analyses, depending on the timing.

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The final analysis will occur when the last participant has completed the final visit of the schedule
of assessment (Day 365±30 days) or discontinued earlier. Final analyses will allow for
determination of the durability of the immune response and analyze any additional safety and
immunological data collected after the additional analysis.
The SAP will describe the planned analyses in greater detail.
Based on safety and immunogenicity results, the sponsor’s Vaccine Development Committee will
decide which regimen will be taken forward. Additional factors such as data from other assays,
literature, epidemiology data, manufacturability, and ease of administration will be taken into
account to select the regimen for the next clinical study.
9.6. 
Data Monitoring Committee or Other Review Board
A DRC  will be established as noted in  Committees Structure in  Section 10.3, Appendix 3,
Regulatory, Ethical, and Study Oversight Considerations.

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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Abbreviations
ADCC  
antibody-dependent cell-mediated cytotoxicity
AE 
adverse event
Al(OH)3 
aluminum hydroxide
ALT  
alanine aminotransferase
AST  
aspartate aminotransferase
bnAbs 
broadly neutralizing antibodies
BUN  
blood urea nitrogen
CDC  
Centers for Disease Control and Prevention
CI 
confidence interval
COVID-19 
coronavirus disease 2019
CPK  
creatine phosphokinase
CTM  
Clinical Trial Manager
CRO  
Contract Research Organization
DIC  
disseminated intravascular coagulation
DRC  
Data Review Committee
eCRF  
electronic case report form
eDC  
electronic data capture
ELISA  
enzyme-linked immunosorbent assay
EU  
European Union
FAS  
full analysis set
FcγR  
Fc gamma receptor
FDA  
US Food and Drug Administration
FIH  
first-in-human
Flu-iiQTM  
Influenza Intensity and Impact Questionnaire
G1 
Group 1
GCP  
Good Clinical Practice
GLP  
Good Laboratory Practice
GMT  
geometric mean titer
HA  
hemagglutinin
HAI 
hemagglutination inhibition
hCG  
human chorionic gonadotropin
HIV  
human immunodeficiency virus
hpf 
high power field
HPV  
humanpapillomavirus
ICF  
informed consent form
ICH  
International Council for Harmonisation
ICMJE  
International Committee of Medical Journal Editors
IEC  
Independent Ethics Committee
Ig 
immunoglobulin
ILI 
influenza-like illness
IM  
intramuscular
IPPI 
investigational product preparation instructions
IRB  
Institutional Review Board
IV  
Intravenous
IWRS  
interactive web response system
LLN  
lower limit of normal
LTM  
Local Trial Manager
MedDRA  
medical dictionary for regulatory activities
mini-HA  
hemagglutinin stem-derived protein vaccine antigen
ML 
medical leader
NSAID  
non-steroidal anti-inflammatory drug
PCC  
protocol clarification communication
PI 
principal investigator
PPI 
per-protocol immunogenicity

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PQC  
Product quality compliant
PRBC  
packed red blood cell
RBC  
red blood cell
RNA  
ribonucleic acid
RSV  
respiratory syncytial virus
RT-PCR  
reverse transcriptase polymerase chain reaction
SAE 
serious adverse event
SAM  
Synthetic Absorptive Matrix strips
SAP  
statistical analysis plan
SIPPM  
Site Investigational Product and Procedures Manual
SoA  
Schedule of Activities
SRP  
study responsible physician
SSG  
statistical support group
SUSAR  
suspected unexpected serious adverse reaction
TOC  
table of contents
ULN  
upper limit or normal
Uniflu  
universal influenza (vaccine)
US  
United States
WBC  
white blood cell

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10.2. Appendix 2: Contraceptive Guidance and Collection of Pregnancy
Information
Participants must follow contraceptive measures as outlined in Section 5.1, Inclusion Criteria.
Pregnancy information will be collected and reported as noted in Section 8.3.5, Pregnancy and
Section 10.4, Appendix 4 Adverse Events: Definitions and Procedures for Recording, Evaluating,
Follow-up, and Reporting.
Definitions
Female Participant of Childbearing Potential
A female participant is considered fertile following menarche and until becoming postmenopausal
unless permanently sterile (see below).
Female Participant Not of Childbearing Potential
 
premenarchal
A premenarchal state is one in which menarche has not yet occurred.
 
postmenopausal
A postmenopausal state is defined as no menses for 12 months without an alternative medical
cause.
 
permanently sterile (for the purpose of this study)
- Permanent sterilization methods include hysterectomy, or bilateral salpingectomy, or
bilateral oophorectomy.
- Has congenital abnormalities resulting in sterility.
Note: If the childbearing potential changes after start of the study (eg, a premenarchal female
participant experiences menarche) or the risk of pregnancy changes (eg, a female participant who
is not heterosexually active becomes active), a female participant must begin a highly effective
method of contraception, as described throughout the inclusion criteria.

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10.3. Appendix 3: Regulatory, Ethical, and Study Oversight Considerations
REGULATORY AND ETHICAL CONSIDERATIONS
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the
protocol, current International Council on Harmonisation (ICH) guidelines on Good Clinical
Practice (GCP), and applicable regulatory and country-specific requirements.
Good Clinical Practice is an international ethical and scientific quality standard for designing,
conducting, recording, and reporting studies that involve the participation of human participants.
Compliance with this standard provides public assurance that the rights, safety, and well-being of
study participants are protected, consistent with the principles that originated in the Declaration of
Helsinki, and that the study data are credible.
Protocol Clarification Communications
If text within a final approved protocol requires clarification (eg, current wording is unclear or
ambiguous) that does not change any aspect of the current study conduct, a protocol clarification
communication (PCC) may be prepared. The PCC Document will be communicated to the
Investigational Site, Site Monitors, Local Trial Managers (LTMs), Clinical Trial Managers
(CTMs), and/or Contract Research Organizations (CROs) who will ensure that the PCC
explanations are followed by the investigators.
The PCC Document may be shared by the sites with IECs/IRBs per local regulations.
The PCC Documents must NOT be used in place of protocol amendments, but the content of the
PCC Document must be included in any future protocol amendments.
Protocol Amendments
Neither the investigator nor the sponsor will modify this protocol without a formal amendment by
the sponsor. All protocol amendments must be issued by the sponsor, 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 to eliminate immediate hazards to the participants, 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 the sponsor. When the
change(s) involve only logistic or administrative aspects of the study, the IEC/IRB (where
required) only needs to be notified.
In situations where a departure from the protocol is unavoidable, the investigator or other physician
in attendance will contact the appropriate sponsor representative listed in the Contact Information
page(s), which will be provided as a separate document. Except in emergency situations, this
contact should be made before implementing any departure from the protocol. In all cases, contact
with the sponsor must be made as soon as possible to discuss the situation and agree on an
appropriate course of action. The data recorded in the eCRF and source documents will reflect any

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departure from the protocol, and the source documents will describe this departure and the
circumstances requiring it.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities
in each respective country, if applicable. A study may not be initiated until all local regulatory
requirements are met.
Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study vaccine to the
study site:
 
Protocol and amendment(s), if any, signed and dated by the principal investigator
 
A copy of the dated and signed (or sealed, where appropriate per local regulations), written
IEC/IRB approval of the protocol, amendments, ICF, any recruiting materials, and if
applicable, participant compensation programs. This approval must clearly identify the
specific protocol by title and number and must be signed (or sealed, where appropriate per
local regulations) by the chairman or authorized designee.
 
Name and address of the IEC/IRB, including a current list of the IEC/IRB members and their
function, with a statement that it is organized and operates according to GCP and the
applicable laws and regulations. If accompanied by a letter of explanation, or equivalent, from
the IEC/IRB, a general statement may be substituted for this list. If an investigator or a
member of the study-site personnel is a member of the IEC/IRB, documentation must be
obtained to state that this person did not participate in the deliberations or in the vote/opinion
of the study.
 
Regulatory authority approval or notification, if applicable
 
Signed and dated statement of investigator (eg, Form FDA 1572), if applicable
 
Documentation of investigator qualifications (eg, curriculum vitae)
 
Completed investigator financial disclosure form from the principal investigator, where
required
 
Signed and dated clinical trial agreement, which includes the financial agreement
 
Any other documentation required by local regulations
The following documents must be provided to the sponsor before enrollment of the first
participant:
 
Completed investigator financial disclosure forms from all subinvestigators
 
Documentation of subinvestigator qualifications (eg, curriculum vitae)
 
Name and address of any local laboratory conducting tests for the study, and a dated copy of
current laboratory normal ranges for these tests, if applicable
 
Local laboratory documentation demonstrating competence and test reliability
(eg, accreditation/license), if applicable

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Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or sponsor where required) will provide the IEC/IRB
with current and complete copies of the following documents (as required by local regulations):
 
Final protocol and, if applicable, amendments
 
Sponsor-approved ICF (and any other written materials to be provided to the participants)
 
IB (or equivalent information) and amendments/addenda
 
Sponsor-approved participant recruiting materials
 
Information on compensation for study-related injuries or payment to participants for
participation in the study, if applicable
 
Investigator's curriculum vitae or equivalent information (unless not required, as documented
by the IEC/IRB)
 
Information regarding funding, name of the sponsor, institutional affiliations, other potential
conflicts of interest, and incentives for participants
 
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, with no consequences for
participants, data or study conduct, unless required locally), the ICF, applicable recruiting
materials, and participant compensation programs, and the sponsor 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.
During the study the investigator (or sponsor where required) will send the following documents
and updates to the IEC/IRB for their review and approval, where appropriate:
 
Protocol amendments (excluding the ones that are purely administrative, with no
consequences for participants, data or study conduct)
 
Revision(s) to ICF and any other written materials to be provided to participants
 
If applicable, new or revised participant recruiting materials approved by the sponsor
 
Revisions to compensation for study-related injuries or payment to participants for
participation in the study, if applicable
 
New edition(s) of the IB and amendments/addenda
 
Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at
least annually)
 
Reports of AEs that are serious, unlisted/unexpected, and associated with the study vaccine
 
New information that may adversely affect the safety of the participants or the conduct of the
study
 
Deviations from or changes to the protocol to eliminate immediate hazards to the participants

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 
Report of deaths of participants under the investigator's care
 
Notification if a new investigator is responsible for the study at the site
 
Development Safety Update Report and Line Listings, where applicable
 
Any other requirements of the IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no
consequences for participants, data or study conduct), the amendment and applicable ICF revisions
must be submitted promptly to the IEC/IRB for review and approval before implementation of the
change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB about
the study completion.
Country Selection
This studywill only be conducted in those countries where the intent is to launch or otherwise help
ensure access to the developed product if the need for the product persists, unless explicitly
addressed as a specific ethical consideration in Section 4.2.1, Study-Specific Ethical Design
Considerations.
Other Ethical Considerations
For study-specific ethical design considerations, refer to Section  4.2.1, Study-Specific Ethical
Design Considerations.
FINANCIAL DISCLOSURE
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial
information in accordance with local regulations to allow the sponsor to submit complete and
accurate financial certification or disclosure statements to the appropriate regulatory authorities.
Investigators are responsible for providing information on financial interests during the course of
the study and for 1 year after completion of the study.
Refer to Required Prestudy Documentation (above) for details on financial disclosure.
INFORMED CONSENT PROCESS
Each participant must give written consent according to local requirements after the nature of the
study has been fully explained. The ICF(s) must be signed before performance of any study-related
activity. The ICF(s) that is/are used must be approved by both the sponsor and by the reviewing
IEC/IRB and be in a language that the participant can read and understand. 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 sponsor policy.
Informed consent may be obtained remotely per local regulations.

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Before enrollment in the study, the investigator or an authorized member of the study-site
personnel must explain to potential participants the aims, methods, reasonably anticipated benefits,
and potential hazards of the study, and any discomfort participation in the study may entail.
Participants will be informed that their participation is voluntary and that they may withdraw
consent to participate at any time. They will be informed that choosing not to participate will not
affect the care the participant will receive. Finally, they will be told that the investigator will
maintain a participant identification register for the purposes of long-term follow-up if needed and
that their records may be accessed by health authorities and authorized sponsor personnel without
violating the confidentiality of the participant, to the extent permitted by the applicable law(s) or
regulations. By signing the ICF the participant is authorizing such access. It also denotes that the
participant agrees to allow his or her study physician to recontact the participant for the purpose
of obtaining consent for additional safety evaluations, if needed.
The participant will be given sufficient time to read the ICF and the opportunity to ask questions.
After this explanation and before entry into the study, consent should be appropriately recorded by
means of the participant's personally dated signature. After having obtained the consent, a copy of
the ICF must be given to the participant.
Participants who are rescreened are required to sign a new ICF.
If the participant is unable to read or write, an impartial witness should be present for the entire
informed consent process (which includes reading and explaining all written information) and
should personally date and sign the ICF after the oral consent of the participant is obtained.
DATA PROTECTION
Privacy of Personal Data
The collection and processing of personal data from participants enrolled in this study will be
limited to those data that are necessary to fulfill the objectives of the study.
These data must be collected and processed with adequate 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 put in place.
Sponsor personnel whose responsibilities require access to personal data agree to keep the identity
of participants confidential.
The informed consent obtained from the participant includes explicit consent for the processing of
personal data and for the investigator/institution to allow direct access to his or her original medical
records (source data/documents) for study-related monitoring, audit, IEC/IRB review, and
regulatory inspection. This consent also addresses the transfer of the data to other entities and to
other countries.
The participant has the right to request through the investigator access to his or her personal data
and the right to request rectification of any data that are not correct or complete. Reasonable steps

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will be taken to respond to such a request, taking into consideration the nature of the request, the
conditions of the study, and the applicable laws and regulations.
In the event of a data security breach, the sponsor will apply measures to adequately manage and
mitigate possible adverse effects taking into consideration the nature of the data security breach as
necessary to address other obligations such as notifying appropriate authorities in accordance with
applicable data protection law.
Exploratory research is not conducted under standards appropriate for the return of data to
participants. In addition, the sponsor cannot make decisions as to the significance of any findings
resulting from exploratory research. Therefore, exploratory research data will not be returned to
participants or investigators, unless required by law or local regulations. Privacy and
confidentiality of data generated in the future on stored samples will be protected by the same
standards applicable to all other clinical data.
LONG-TERM RETENTION OF SAMPLES FOR ADDITIONAL FUTURE RESEARCH
No additional research on study participants, study samples, or data derived from the study will be
conducted by the institution(s) or by a third party, without the prior written consent of the sponsor.
Samples collected in this study may be stored for up to 15 years (or according to local regulations)
for additional research. Samples will only be used to understand vaccines, to understand
differential vaccine responders, to understand the study intervention platform, to develop
tests/assays related to vaccines, to understand influenza or other respiratory diseases, and may
include RNA testing. The research may begin at any time during the study or the post-study storage
period.
Stored samples will be coded throughout the sample storage and analysis process and will not be
labeled with personal identifiers. Participants may withdraw their consent for their samples to be
stored for research (refer to Section 7.2.1, Withdrawal From the Use of Research Samples).
COMMITTEE STRUCTURE
Data Review Committee
An internal DRC, consisting of members that are not directly involved in the study conduct, data
management, or statistical analysis, will be established for this study, and will monitor data to
ensure the safety and well-being of the participants enrolled. The DRC will review data as
indicated in Section 4.1, Overall Design. When appropriate, the conclusions of the DRC will be
communicated to the investigators, the IRB/IEC, and the national regulatory authorities.
The DRC will specifically review safety data (solicited and unsolicited AEs, SAEs, and available
laboratory assessments) 7-day post-first and post-second dose in each cohort (participants in the
sentinel and safety ramp-up subset).
In addition, ad hoc review may be performed further to the occurrence of any AE/SAE leading to
a study pausing situation as outlined in Section 6.8, Study Pausing Rules, or at request of the

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sponsor’s medical officer or designee. The PI(s) and SRP  will inform the DRC  of any AE of
concern.
The DRC will review blinded data first, but is entitled to and has the right to require submission
of unblinded data if deemed necessary.
It will also be possible for the DRC to review unblinded immunogenicity data during the course
of the study if this is deemed necessary for future vaccine development-related decisions. If this is
the case, a biomarker representative (not involved in the conduct of the study) will be part of the
DRC.
The DRC will include medical experts in vaccines and at least one statistician. The DRC can
include members from both inside and outside of the sponsor, but will not include any study team
personnel or people otherwise directly involved in the study conduct, data management, or
statistical analysis for the study. The DRC responsibilities, authorities, and procedures will be
documented in its charter.
PUBLICATION POLICY/DISSEMINATION OF CLINICAL STUDY DATA
All information, including but not limited to information regarding INFLUENZA G1 mHA or the
sponsor's operations (eg, patent application, formulas, manufacturing processes, basic scientific
data, prior clinical data, formulation information) supplied by the sponsor to the investigator and
not previously published, and any data, including exploratory biomarker research data, generated
as a result of this study, are considered confidential and remain the sole property of the sponsor.
The investigator agrees to maintain this information in confidence and use this information only
to accomplish this study and will not use it for other purposes without the sponsor's prior written
consent.
The investigator understands that the information developed in the study will be used by the
sponsor in connection with the continued development of INFLUENZA G1 mHA, and thus may
be disclosed as required to other clinical investigators or regulatory agencies. To permit the
information derived from the clinical studies to be used, the investigator is obligated to provide
the sponsor with all data obtained in the study.
The results of the study will be reported in a Clinical Study Report generated by the sponsor and
will contain data from all study sites that participated in the study as per protocol. Recruitment
performance or specific expertise related to the nature and the key assessment parameters of the
study will be used to determine a coordinating investigator for the study. Results of exploratory
biomarker analyses performed after the Clinical Study Report has been issued will be reported in
a separate report and will not require a revision of the Clinical Study Report.
Study participant identifiers will not be used in publication of results. Any work created in
connection with performance of the study and contained in the data that can benefit from copyright
protection (except any publication by the investigator as provided for below) shall be the property
of the sponsor as author and owner of copyright in such work.

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Consistent with Good Publication Practices and International Committee of Medical Journal
Editors (ICMJE) guidelines, the sponsor shall have the right to publish such primary (multicenter)
data and information without approval from the investigator. The investigator has the right to
publish study site-specific data after the primary data are published. If an investigator wishes to
publish information from the study, a copy of the manuscript must be provided to the sponsor for
review at least 60 days before submission for publication or presentation. Expedited reviews will
be arranged for abstracts, poster presentations, or other materials. If requested by the sponsor in
writing, the investigator will withhold such publication for up to an additional 60 days to allow for
filing of a patent application. In the event that issues arise regarding scientific integrity or
regulatory compliance, the sponsor will review these issues with the investigator. The sponsor will
not mandate modifications to scientific content and does not have the right to suppress information.
For multicenter study designs and sub-study approaches, secondary results generally should not
be published before the primary endpoints of a study have been published. Similarly, investigators
will recognize the integrity of a multicenter study by not submitting for publication data derived
from the individual study site until the combined results from the completed study have been
submitted for publication, within 18 months after the study end date, or the sponsor confirms there
will be no multicenter study publication. Authorship of publications resulting from this study will
be based on the guidelines on authorship, such as those described in the ICMJE Recommendations
for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals, which
state that the named authors must have made a significant contribution to the conception or design
of the work; or the acquisition, analysis, or interpretation of the data for the work; and drafted the
work or revised it critically for important intellectual content; and given final approval of the
version to be published; and agreed to be accountable for all aspects of the work in ensuring that
questions related to the accuracy or integrity of any part of the work are appropriately investigated
and resolved.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and disclose the existence of and the results of clinical studies as required
by law. The disclosure of the final study results will be performed after the end of study in order
to ensure the statistical analyses are relevant.
DATA QUALITY ASSURANCE
Data Quality Assurance/Quality Control
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified
investigators and appropriate study sites, review of protocol procedures with the investigator and
study-site personnel before the study, and periodic monitoring visits by the sponsor. Written
instructions will be provided for collection, handling, storage, and shipment of samples.
Guidelines for eCRF completion will be provided and reviewed with study-site personnel before
the start of the study.
The sponsor will review eCRF for accuracy and completeness during on-site and/or remote
monitoring visits and after transmission to the sponsor; any discrepancies will be resolved with the

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investigator or designee, as appropriate. After upload of the data into the study database they will
be verified for accuracy and consistency with the data sources.
CASE REPORT FORM COMPLETION
Case report forms are prepared and provided by the sponsor for each participant in electronic
format. All data relating to the study must be recorded in eCRF. All eCRF entries, corrections, and
alterations must be made by the investigator or authorized study-site personnel. The investigator
must verify that all data entries in the eCRF are accurate and correct.
The study data will be transcribed by study-site personnel from the source documents onto an
eCRF, if applicable. Study-specific data will be transmitted in a secure manner to the sponsor.
Worksheets may be used for the capture of some data to facilitate completion of the eCRF. Any
such worksheets will become part of the participant's source documents. Data must be entered into
eCRF in English. The eCRF must be completed as soon as possible after a participant visit and the
forms should be available for review at the next scheduled monitoring visit.
All participative measurements (eg, pain scale information or other questionnaires) will be
completed by the same individual who made the initial baseline determinations whenever possible.
If necessary, queries will be generated in the eDC tool. If corrections to an eCRF are needed after
the initial entry into the eCRF, this can be done in either of the following ways:
 Investigator and study-site personnel can make corrections in the eDC tool at their own
initiative or as a response to an auto query (generated by the eDC tool).
 Sponsor or sponsor delegate can generate a query for resolution by the investigator and study-
site personnel.
SOURCE DOCUMENTS
At a minimum, source documents consistent in the type and level of detail with that commonly
recorded at the study site as a basis for standard medical care must be available for the following:
participant identification, eligibility, and study identification; study discussion and date of signed
informed consent; dates of visits; results of safety and efficacy parameters as required by the
protocol; record of all AEs and follow-up of AEs; concomitant medication; intervention
receipt/dispensing/return records; study vaccine administration information; and date of study
completion and reason for early discontinuation of study vaccine or withdrawal from the study, if
applicable.
The author of an entry in the source documents should be identifiable.
Participant- and investigator-completed scales and assessments designated by the sponsor (ie,
diary, Flu-iiQTM questionnaire, ILI form) will be recorded and will be considered source data. The
participant’s diary used to collect information regarding solicited signs and symptoms after
vaccination will be considered source data.

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Specific details required as source data for the study and source data collection methods will be
reviewed with the investigator before the study and will be described in the monitoring guidelines
(or other equivalent document).
An eSource system may be utilized, which contains data traditionally maintained in a hospital or
clinic record to document medical care (eg, electronic source documents) as well as the clinical
study-specific data fields as determined by the protocol. This data is electronically extracted for
use by the sponsor. If eSource is utilized, references made to the eCRF in the protocol include the
eSource system but information collected through eSource may not be limited to that found in the
eCRF.
MONITORING
The sponsor will use a combination of monitoring techniques (central, remote, or on-site
monitoring) to monitor this study.
The sponsor will perform on-site monitoring visits as frequently as necessary. The monitor will
record dates of the visits in a study site visit log that will be kept at the study site. The first post-
initiation visit will be made as soon as possible after enrollment has begun. At these visits, the
monitor will compare data entered into the eCRF with the source documents (eg,
hospital/clinic/physician’s office medical records); a sample may be reviewed. The nature and
location of all source documents will be identified to ensure that all sources of original data
required to complete the eCRF are known to the sponsor and study-site personnel and are
accessible for verification by the sponsor study-site contact. If electronic records are maintained
at the study site, the method of verification must be discussed with the study-site personnel.
Direct access to source documents (medical records) must be allowed for the purpose of verifying
that the recorded data are consistent with the original source data. Findings from this review will
be discussed with the study-site personnel. The sponsor expects that, during monitoring visits, the
relevant study-site personnel will be available, the source documents will be accessible, and a
suitable environment will be provided for review of study-related documents. The monitor will
meet with the investigator on a regular basis during the study to provide feedback on the study
conduct.
In addition to on-site monitoring visits, remote contacts can occur. It is expected that during these
remote contacts, study-site personnel will be available to provide an update on the progress of the
study at the site.
Central monitoring will take place for data identified by the sponsor as requiring central review.
ON-SITE AUDITS
Representatives of the sponsor's clinical quality assurance department may visit the study site at
any time during or after completion of the study to conduct an audit of the study in compliance
with regulatory guidelines and company policy. These audits will require access to all study
records, including source documents, for inspection. Participant privacy must, however, be

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respected. The investigator and study-site personnel are responsible for being present and available
for consultation during routinely scheduled study-site audit visits conducted by the sponsor or its
designees.
Similar auditing procedures may also be conducted by agents of any regulatory body, either as part
of a national GCP compliance program or to review the results of this study in support of a
regulatory submission. The investigator should immediately notify the sponsor if he or she has
been contacted by a regulatory agency concerning an upcoming inspection.
RECORD RETENTION
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all eCRF
and all source documents that support the data collected from each participant, as well as all study
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a Clinical
Trial, and all study documents as specified by the applicable regulatory requirement(s). The
investigator/institution will take measures to prevent accidental or premature destruction of these
documents.
Essential documents must be retained until at least 2 years after the last approval of a marketing
application in an ICH region and until there are no pending or contemplated marketing applications
in an ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical
development of the investigational product. These documents will be retained for a longer period
if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the
responsibility of the sponsor to inform the investigator/institution as to when these documents no
longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the
responsibility of keeping the study records, custody must be transferred to a person who will accept
the responsibility. The sponsor 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
before having obtained written approval from the sponsor.
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any
documentation relating to this study, the investigator/institution must permit access to such reports.
STUDY AND SITE START AND CLOSURE
First Act of Recruitment
The first site open is considered the first act of recruitment and it becomes the study start date.
Study Termination
The sponsor reserves the right to close the study site or terminate the study at any time for any
reason at the sole discretion of the sponsor. Study sites will be closed upon study completion. A
study site is considered closed when all required documents and study supplies have been collected
and a study-site closure visit has been performed.

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The investigator may initiate study-site closure at any time, provided there is reasonable cause and
sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are not
limited to:
 Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or
local health authorities, the sponsor's procedures, or GCP guidelines
 Inadequate recruitment of participants by the investigator
 Discontinuation of further study vaccine development

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10.4. Appendix 4: Adverse Events: Definitions and Procedures for Recording,
Evaluating, Follow-up, and Reporting
ADVERSE EVENT DEFINITIONS AND CLASSIFICATIONS
Adverse Event
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal
(investigational or non-investigational) product. An AE does not necessarily have a causal
relationship with the intervention. An AE can therefore be any unfavorable and unintended sign
(including an abnormal finding), symptom, or disease temporally associated with the use of a
medicinal (investigational or non-investigational) product, whether or not related to that medicinal
(investigational or non-investigational) product. (Definition per ICH)
This includes any occurrence that is new in onset or aggravated in severity or frequency from the
baseline condition, or abnormal results of diagnostic procedures, including laboratory test
abnormalities.
Note: For time period of sponsor’s AE collection, see All Adverse Events under Section 8.3.1,
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event Information.
Any ILI and complications related to ILIs will be reported as an AE if it occurs between the time
of any vaccination through the following 28 days. An ILI and complications related to ILIs that
occur outside of this period does not require AE reporting unless ongoing at the time of subsequent
vaccination.
Serious Adverse Event
An SAE based on ICH and European Union (EU) Guidelines on Pharmacovigilance for Medicinal
Products for Human Use is any untoward medical occurrence that at any dose:
 
Results in death
 
Is life-threatening
(The participant was 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.)
 
Requires inpatient hospitalization or prolongation of existing hospitalization
 
Results in persistent or significant disability/incapacity
 
Is a congenital anomaly/birth defect
 
Is a suspected transmission of any infectious agent via a medicinal product
 
Is Medically Important*
*Medical and scientific judgment should be exercised in deciding whether expedited reporting is
also appropriate in other situations, such as important medical events that may not be immediately
life-threatening or result in death or hospitalization but may jeopardize the participant or may

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require intervention to prevent one of the other outcomes listed in the definition above. These
should usually be considered serious.
If a serious and unexpected AE occurs for which there is evidence suggesting a causal relationship
between the study vaccine and the event (eg, death from anaphylaxis), the event must be reported
as a serious and unexpected suspected adverse reaction even if it is a component of the study
endpoint (eg, all-cause mortality).
Any ILI and complications related to ILIs fulfilling the criteria of an SAE will be reported as such
during the entire study period from the first vaccination.
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An AE is considered unlisted if the nature or severity is not consistent with the applicable product
reference safety information. For INFLUENZA G1 mHA, the expectedness of an AE will be
determined by whether or not it is listed in the IB.
ATTRIBUTION DEFINITIONS
Assessment of Causality
The causal relationship to study vaccine is determined by the investigator. The following selection
should be used to assess all AEs.
Related
There is a reasonable causal relationship between study treatment administration and the AE.
Not Related
There is not a reasonable causal relationship between study treatment administration and the AE.
The term "reasonable causal relationship" means there is evidence to support a causal relationship.
By definition, all solicited AEs at the injection site will be considered related to the study vaccine
administration.
SEVERITY CRITERIA
All AEs and laboratory data will be coded for severity using a modified version of the FDA grading
table, based on version of September 2007 (FDA 2007), included in Section 10.5 Appendix 5,
Toxicity Grading Scale.
For AEs not identified in the grading table, the following guidelines will be applied:

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Grade 1 
Mild 
Symptoms causing no or minimal interference with usual social
and functional activities
Grade 2 
Moderate 
Symptoms causing greater than minimal interference with usual
social and functional activities
Grade 3 
Severe 
Symptoms causing inability to perform usual social and
functional activities and requires medical intervention
Grade 4 
Potentially 
life- 
threatening 
Symptoms causing inability to perform basic self-care functions
OR medical or operative intervention indicated to prevent
permanent impairment, persistent disability OR emergency room
visit or hospitalization
The severity of solicited signs and symptoms will be graded in the diary by the participant based
on the severity assessment provided in the diary and then verified by the investigator using scoring
system shown in Table 6 and Table 7 as follows (Note: severity of the measured events will be
derived from the diameter [for erythema and swelling] and the temperature measurements [for
fever]):
Adults/adolescents (≥12 years of age)
Table 6: 
Severity Assessment: Solicited Injection Site Events - Adults/Adolescents (≥12 years of age)
Grade 
Definition
0 
No pain/tenderness;
Diameter of erythema, swelling<25 mm.
1 
Aware of symptoms but easily tolerated;
Does not interfere with activity;
Discomfort only to touch;
Diameter of erythema, swelling ≥25 mm and <50 mm.
2 
Notable symptoms;
Requires modification in activity or use of medications;
Discomfort with movement;
Diameter of erythema, swelling ≥50 mm and <100 mm.
3 
Incapacitating symptoms;
Inability to do work, school, or usual activities;
Use of narcotic pain reliever;
Diameter of erythema, swelling ≥100 mm.
4 
Hospitalization;
Pain/tenderness causing inability to perform basic self-care function;
For erythema, swelling: necrosis or exfoliative dermatitis.

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Table 7: 
Severity Assessment: Solicited Systemic Events - Adults/Adolescents (≥12 years of age)
Grade 
Definition
0 
Absent;
Fever/Pyrexia: Below 38.0°C or 100.4°F.
1 
Minimal symptoms;
Causes minimal or no interference with work, school, or self-care activities;
Fever/Pyrexia: 38.0 - 38.4°C or 100.4 - 101.1°F.
2 
Notable symptoms;
Requires modification in activity or use of medications;
Does NOT result in loss of work, school, or cancellation of social activities;
Fever/Pyrexia: 38.5 - 38.9°C or 101.2 - 102.0°F.
3 
Incapacitating symptoms;
Requires bed rest or results in loss of work, school, or cancellation of social activities;
Use of narcotic pain reliever;
Fever/Pyrexia: 39.0 - 40.0°C or 102.1 - 104.0°F.
4 
Hospitalization;
Inability to perform basic self-care functions;
Fever/Pyrexia: Greater than 40°C or 104.0°F.
SPECIAL REPORTING SITUATIONS
Safety events of interest on a sponsor study vaccine in an interventional study that may require
expedited reporting or safety evaluation include, but are not limited to:
 
Overdose of a sponsor study vaccine
 
Suspected abuse/misuse of a sponsor study vaccine
 
Accidental or occupational exposure to a sponsor study vaccine
 
Medication error, intercepted medication error, or potential medication error involving a
Johnson & Johnson medicinal product (with or without patient exposure to the Johnson &
Johnson medicinal product, eg, product name confusion, product label confusion, intercepted
prescribing or dispensing errors)
 
Exposure to a sponsor study vaccine from breastfeeding
 
Reporting of participant pregnancy or participant partner(s) pregnancy
Participant-specific special reporting situations should be recorded in the eCRF. Any special
reporting situation that meets the criteria of an SAE should be recorded on the SAE page of the
eCRF.
PROCEDURES
All Adverse Events
All AEs, regardless of seriousness, severity, or presumed relationship to study vaccine, must be
recorded using medical terminology in the source document and the eCRF. Whenever possible,
diagnoses should be given when signs and symptoms are due to a common etiology (eg, cough,
runny nose, sneezing, sore throat, and head congestion should be reported as "upper respiratory
infection"). Investigators must record in the eCRF their opinion concerning the relationship of the
AE to study therapy. All measures required for AE management must be recorded in the source
document and reported according to sponsor instructions.

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For all studies with an outpatient phase, including open-label studies, the participant must be
provided with a "wallet (study) card" and instructed to carry this card with them for the duration
of the study indicating the following:
 
Study number
 
Statement, in the local language(s), that the participant is participating in a clinical study
 
Investigator's name and 24-hour contact telephone number
 
Local sponsor's name and 24-hour contact telephone number (for medical personnel only)
 
Site number
 
Participant number
 
Any other information that is required to do an emergency breaking of the blind
Serious Adverse Events
All SAEs that have not resolved by the end of the study, or that have not resolved upon
discontinuation of the participant's participation in the study, must be followed until any of the
following occurs:
 
The event resolves
 
The event stabilizes
 
The event returns to baseline, if a baseline value/status is available
 
The event can be attributed to agents other than the study vaccine or to factors unrelated to
study conduct
 
It becomes unlikely that any additional information can be obtained (participant or health care
practitioner refusal to provide additional information, lost to follow-up after demonstration of
due diligence with follow-up efforts)
Suspected transmission of an infectious agent by a medicinal product will be reported as an SAE.
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during the
course of a participant's participation in a study must be reported as an  SAE, except
hospitalizations for the following:
 
Hospitalizations not intended to treat an acute illness or AE (eg, social reasons such as pending
placement in long-term care facility)
 
Surgery or procedure planned before entry into the study (must be documented in the eCRF).
Note: Hospitalizations that were planned before the signing of the ICF, and where the
underlying condition for which the hospitalization was planned has not worsened, will not be
considered SAEs. Any AE that results in a prolongation of the originally planned
hospitalization is to be reported as a new SAE.
The cause of death of a participant in a study, whether or not the event is expected or associated
with the study vaccine, is considered an SAE.

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Information regarding SAEs will be transmitted to the sponsor using an SAE reporting form and
the eCRF form for AEs, which must be completed and reviewed by a physician from the study
site, and transmitted in a secure manner to the sponsor immediately, but no later than 24 hours of
their knowledge of the event. The initial and follow-up reports of an SAE should be transmitted in
a secure manner electronically or by facsimile (fax). Telephone reporting should be the exception
and the reporter should be asked to complete the appropriate form(s) first.
CONTACTING SPONSOR REGARDING SAFETY
The names (and corresponding telephone numbers) of the individuals who should be contacted
regarding safety issues or questions regarding the study are listed in the Contact Information
page(s), which will be provided as a separate document.
PRODUCT QUALITY COMPLAINT HANDLING
A PQC is defined as any suspicion of a product defect related to manufacturing, labeling, or
packaging, ie, any dissatisfaction relative to the identity, quality, durability, or reliability of a
product, including its labeling or package integrity. A PQC may have an impact on the safety and
efficacy of the product. Timely, accurate, and complete reporting and analysis of PQC information
from studies are crucial for the protection of participants, investigators, and the sponsor, and are
mandated by regulatory agencies worldwide. The sponsor has established procedures in
conformity with regulatory requirements worldwide to ensure appropriate reporting of PQC
information; all studies conducted by the sponsor or its affiliates will be conducted in accordance
with those procedures.
Procedures
All initial PQCs must be reported to the sponsor by the study-site personnel immediately, but no
later than 24 hours after being made aware of the event.
If the defect is combined with an SAE, the study-site personnel must report the PQC to the sponsor
according to the SAE reporting timelines (refer to Section 8.3.1, Time Period and Frequency for
Collecting Adverse Event and Serious Adverse Event Information). A sample of the suspected
product should be maintained for further investigation if requested by the sponsor.
Contacting Sponsor Regarding Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted
regarding product quality issues are listed in the Contact Information page(s), which will be
provided as a separate document.

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10.5. Appendix 5: Toxicity Grading Scale
Adapted from the FDA Guidance document “Toxicity Grading Scale for Healthy Adult and
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials” (September 2007)
A: Tables for Clinical Abnormalities
Local Reaction to 
Injectable Product 
Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life
Threatening
(Grade 4)
Pain/Tenderness# 
Aware of symptoms 
but easily tolerated; 
Does not interfere 
with activity; 
Discomfort only to 
touch  
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Discomfort with 
movement 
Incapacitating 
symptoms; 
Inability to do work, 
school, or usual 
activities; Use of 
narcotic pain reliever
Hospitalization;
Pain/tenderness
causing inability to
perform basic self-
care function
Erythema# 
25 –50 mm  
51 –100 mm  
> 100 mm  
Hospitalization;
Necrosis or
exfoliative dermatitis
Swelling# 
25 –50 mm  
51 –100 mm  
> 100 mm  
Hospitalization;
Necrosis
# Revised by the sponsor.
Vital Signs * 
Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life
Threatening
(Grade 4)
Fever (°C) ** 
           (°F)** 
38.0 - 38.4 
100.4 - 101.1 
38.5 - 38.9 
101.2 - 102.0 
39.0 - 40.0 
102.1 - 104.0 
> 40
> 104.0
Tachycardia - beats 
per 
minute
101 –115 
116 –130 
> 130 
Hospitalization for
arrhythmia#
Bradycardia - beats 
per 
minute***
50 –54 
45 –49 
< 45 
Hospitalization for
arrhythmia#
Hypertension 
(systolic) - mm Hg 
141 –150 
151 –155 
> 155 
Hospitalization for
malignant
hypertension#
Hypertension 
(diastolic) - mm Hg 
91 –95 
96 –100 
> 100 
Hospitalization for
malignant
hypertension#
Hypotension 
(systolic) –mm Hg 
85 –89 
80 –84 
< 80 
Hospitalization for
hypotensive shock#
Respiratory Rate – 
breaths per minute
17 –20 
21 –25 
> 25 
Intubation
* Participant should be at rest for all vital sign measurements.
** For oral temperature: no recent hot or cold beverages or smoking.
*** When resting heart rate is between 60 –100 beats per minute. Use clinical judgment when characterizing
bradycardia among some healthy participant populations, for example, conditioned athletes.
# Revised by the sponsor.

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Systemic (General) Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life
Threatening
(Grade 4)
Vomiting# 
No interference 
with activity or 1 –2 
episodes/24 hours 
Some interference 
with activity or > 2 
episodes/24 hours 
Prevents daily  
activity, requires 
outpatient intravenous
(IV) hydration
Hospitalization;
Hypotensive shock
Nausea# 
Minimal symptoms; 
causes minimal or no 
interference with  
work, school, or self- 
care activities 
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Does NOT result in 
loss of work, school, 
or cancellation of 
social activities
Incapacitating 
symptoms; 
Requires bed rest 
and/or results in loss 
of work, school, or
cancellation of social
activities
Hospitalization;
Inability to perform
basic self-care
functions
Diarrhea# 
2 –3 loose stools or 
< 400 gms/24 hours 
4 –5 stools or 
400 –800 gms/24 
hours 
6 or more watery  
stools or 
> 800 gms/24 hours 
or oral rehydration 
necessary
Hospitalization;
Hypotensive shock
OR IV fluid
replacement indicated
Headache# 
Minimal symptoms;
causes minimal or no
interference with
work, school, or self-
care activities
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Does NOT result in 
loss of work, school, 
or cancellation of 
social activities 
Incapacitating
symptoms;
Requires bed rest
and/or results in loss
of work, school, or
cancellation of social
activities;
Use of narcotic pain
reliever
Hospitalization;
Inability to perform
basic self-care
functions
Fatigue# 
Minimal symptoms;
causes minimal or no
interference with
work, school, or self-
care activities
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Does NOT result in 
loss of work, school, 
or cancellation of 
social activities 
Incapacitating
symptoms;
Requires bed rest
and/or results in loss
of work, school, or
cancellation of social
activities;
Use of narcotic pain
reliever
Hospitalization;
Inability to perform
basic self-care
functions
Myalgia# 
Minimal symptoms;
causes minimal or no
interference with
work, school, or self-
care activities
Notable symptoms; 
Requires modification 
in activity or use of 
medications; 
Does NOT result in 
loss of work, school, 
or cancellation of 
social activities 
Incapacitating
symptoms;
Requires bed rest
and/or results in loss
of work, school, or
cancellation of social
activities;
Use of narcotic pain
reliever
Hospitalization;
Inability to perform
basic self-care
functions
# Revised by the sponsor.

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Systemic Illness 
Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life
Threatening
(Grade 4)
Illness or clinical 
adverse 
event (as defined 
according to 
No interference with  
activity  
Some interference 
with activity not 
requiring medical 
intervention
Prevents daily  
activity and requires
medical intervention
Hospitalization#
# Revised by the sponsor.
B. Tables for Laboratory Abnormalities
Laboratory tests may be performed during routine medical care and assessment of AEs or other
medical events based on the investigator’s judgment.
The laboratory values provided in the tables below serve as guidelines and are dependent upon
institutional normal parameters. Institutional normal reference ranges should be provided to
demonstrate that they are appropriate.
Serum * 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life
Threatening
(Grade 4)**
Sodium - Hyponatremia mEq/L 
132 - 134 
130 - 131 
125 - 129 
< 125
Sodium - Hypernatremia mEq/L 
144 - 145 
146 - 147 
148 - 150 
> 150
Potassium - Hyperkalemia mEq/L 
5.1 - 5.2 
5.3 - 5.4 
5.5 - 5.6 
> 5.6
Potassium - Hypokalemia mEq/L 
3.5 - 3.6 
3.3 - 3.4 
3.1 - 3.2 
< 3.1
Glucose - Hypoglycemia mg/dL 
65 - 69 
55 - 64 
45 - 54 
< 45
Glucose - Hyperglycemia 
  Fasting mg/dL 
  Random - mg/dL 
100 - 110 
110 - 125 
111 - 125 
126 - 200 
>125 
>200 
Insulin
requirements or
hyperosmolar
coma
Blood Urea Nitrogen  
(BUN) mg/dL
23 - 26 
27 - 31 
> 31 
Requires dialysis
Creatinine - mg/dL 
1.5 - 1.7 
1.8 - 2.0 
2.1 - 2.5 
> 2.5 or requires
dialysis
Calcium - hypocalcemia mg/dL 
8.0 - 8.4 
7.5 - 7.9 
7.0 - 7.4 
< 7.0
Calcium - hypercalcemia mg/dL 
10.5 - 11.0 
11.1 - 11.5 
11.6 - 12.0 
> 12.0
Magnesium - hypomagnesemia mg/dL 
1.3 - 1.5 
1.1 - 1.2 
0.9 - 1.0 
< 0.9
Phosphorous - hypophosphatemia mg/dL 2.3 - 2.5 
2.0 - 2.2 
1.6 - 1.9 
< 1.6
Creatine phosphokinase 
(CPK) - mg/dL 
1.25 - 1.5 x  
ULN***
1.6 - 3.0 x ULN  3.1 -10 x ULN  
> 10 x ULN
Albumin - Hypoalbuminemia g/dL 
2.8 - 3.1 
2.5 - 2.7 
< 2.5 
--
Total Protein - Hypoproteinemia g/dL 
5.5 - 6.0 
5.0 - 5.4 
< 5.0 
--
Alkaline phosphate - 
increase by factor
1.1 - 2.0 x ULN  2.1 - 3.0 x ULN  3.1 - 10 x ULN  
> 10 x ULN
Liver Function Tests -ALT, AST  
increase by factor
1.1 - 2.5 x ULN  2.6 - 5.0 x ULN  5.1 - 10 x ULN  
> 10 x ULN
Bilirubin - when accompanied 
by any increase in Liver Function Test 
increase by factor
1.1 - 1.25 x ULN  1.26 - 1.5 x 
ULN
1.51 - 1.75 x ULN > 1.75 x ULN

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Serum * 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life
Threatening
(Grade 4)**
Bilirubin - when Liver Function Test 
is normal; increase by factor
1.1 - 1.5 x ULN  1.6 - 2.0 x ULN  2.0 - 3.0 x ULN  > 3.0 x ULN
Cholesterol 
201 - 210 
211 - 225 
> 226 
---
Pancreatic enzymes - amylase, lipase 
1.1 - 1.5 x ULN  1.6 - 2.0 x ULN  2.1 - 5.0 x ULN  > 5.0 x ULN
* 
The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal
parameters. Institutional normal reference ranges should be provided to demonstrate that they are appropriate.
** The clinical signs or symptoms associated with laboratory abnormalities might result in characterization of the
laboratory abnormalities as potentially life-threatening (Grade 4). For example. a low sodium value that falls
within a Grade 3 parameter (125-129 mEq/L) should be recorded as a Grade 4 hyponatremia event if the
participant had a new seizure associated with the low sodium value.
*** ULN is the upper limit of the normal range.
Hematology * 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life
Threatening
(Grade 4)
Hemoglobin (Female) - gm/dL 
11.0 - 12.0 
9.5 - 10.9 
8.0 - 9.4 
< 8.0
Hemoglobin (Female) 
change from baseline value - gm/dL
Any decrease - 1.5 1.6 - 2.0 
2.1 - 5.0 
> 5.0
Hemoglobin (Male) - gm/dL 
12.5 - 13.5 
10.5 - 12.4 
8.5 - 10.4 
< 8.5
Hemoglobin (Male) 
change from baseline value - gm/dL
Any decrease - 1.5 1.6 - 2.0 
2.1 - 5.0 
> 5.0
WBC Increase - cell/mm3 
10,800 - 15,000 
15,001 - 20,000 20,001 - 25, 000 > 25,000
WBC Decrease - cell/mm3 
2,500 - 3,500 
1,500 - 2,499 
1,000 - 1,499 
< 1,000
Lymphocytes Decrease - cell/mm3 
750 - 1,000 
500 - 749 
250 - 499 
< 250
Neutrophils Decrease - cell/mm3 
1,500 - 2,000 
1,000 - 1,499 
500 - 999 
< 500
Eosinophils - cell/mm3 
650 - 1500 
1501 - 5000 
> 5000 
Hypereosinophilic
Platelets Decreased - cell/mm3 
125,000 - 140,000 100,000 - 124,000 25,000 - 99,000 < 25,000
PT - increase by factor 
(prothrombin time) 
1.0 - 1.10 x  
ULN** 
1.11 - 1.20 x 
ULN  
1.21 - 1.25 x 
ULN
> 1.25 ULN
PTT - increase by factor 
(partial thromboplastin time)
1.0 - 1.2 x ULN  
1.21 - 1.4 x ULN  1.41 - 1.5 x ULN  > 1.5 x ULN
Fibrinogen increase - mg/dL 
400 - 500 
501 - 600 
> 600 
--
Fibrinogen decrease - mg/dL 
150 - 200 
125 - 149 
100 - 124 
< 100 or
associated
with gross
bleeding or
disseminated
intravascular
coagulation (DIC)
* 
The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal
parameters. Institutional normal reference ranges should be provided to demonstrate that they are appropriate.
** ULN is the upper limit of the normal range.

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Urine * 
Mild  
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life-Threatening
(Grade 4)
Protein  
Trace 
1+  
2+ 
Hospitalization or
dialysis
Glucose 
Trace 
1+  
2+ 
Hospitalization for hyperglycemia
Blood (microscopic) - 
red blood cells per 
high power field (rbc/hpf) 
1 - 10 
11 - 50 
> 50 and/or 
gross 
blood 
Hospitalization or
packed red blood cells (PRBC)
transfusion
* 
The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal
parameters. Institutional normal reference ranges should be provided to demonstrate that they are appropriate.

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10.6. Appendix 6: Clinical Laboratory Tests
The following tests will be performed according to Section 1.3, Schedule of Activities:
The actual date of assessment and, if required, the actual time of the assessment of laboratory
samples will be recorded in the source documentation and in the eCRF or laboratory requisition
form.
Protocol-Required Safety Laboratory Assessments
Laboratory 
Assessments
Parameters 
Timepoints
Testing done
locally
Hematology
 Platelet count
 Hemoglobin
 White Blood Cell (WBC) count with
Differential: Neutrophils, Lymphocytes,
Monocytes, Eosinophils, and Basophils
Clinical Chemistry
 Sodium
 Potassium
 Blood urea nitrogen (BUN)
 Creatinine
 Aspartate aminotransferase (AST)
 Alanine aminotransferase (ALT)
Serum pregnancy β-hCG test (qualitative;
female 
participants 
of 
childbearing
potential)
According to Section 1.3, Schedule of Activities
Note: A WBC evaluation may include any
abnormal cells, which will then be reported by
the laboratory. In addition, any other abnormal
cells in a blood smear will also be reported.
Testing done
locally
Urine pregnancy test (female participants of 
childbearing potential)
According to Section 1.3, Schedule of Activities
Testing done
locally
Nasal swab for influenza virus testing 
According to Section 1.3, Schedule of Activities
Note: Virology test may be repeated at a central
laboratory upon sponsor request including but
not limited to influenza virus.
Testing done
centrally
Serology blood sample for seroconfirmation 
of influenza virus infection (HAI)
According to Section 1.3, Schedule of Activities
Note: Seroconfimation  test may be performed
including but not limited to HAI assay as
available and applicable.

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10.7. Appendix 7: Study Conduct During a Pandemic
GUIDANCE ON STUDY CONDUCT DURING THE COVID-19 PANDEMIC
It is recognized that the Coronavirus Disease 2019 (COVID-19) pandemic may have an impact on
the conduct of this clinical study due to, for example, isolation or quarantine of participants and
study-site personnel; travel restrictions/limited access to public places, including hospitals; study
site personnel being reassigned to critical tasks.
The sponsor is providing options for study-related participant management in the event of
disruption to the conduct of the study. This guidance does not supersede any local or government
requirements or the clinical judgment of the investigator to protect the health and well-being of
participants and site staff. If, at any time, a participant’s travel to the study site is considered to be
dangerous, study participation may be interrupted, and study follow-up conducted. If it becomes
necessary to discontinue participation in the study, the procedures outlined in the protocol for
discontinuing study intervention will be followed.
If, as a result of the COVID-19 pandemic, scheduled visits cannot be conducted in person at the
study site, they will be performed to the extent possible remotely/virtually or delayed until such
time that on-site visits can be resumed. At each contact, participants will be interviewed to collect
safety data. Key immunogenicity endpoint assessments should be performed if required and as
feasible. Participants will also be questioned regarding general health status to fulfill any physical
examination requirement.
Every effort should be made to adhere to protocol-specified assessments for participants on study
intervention, including follow up. Modifications to protocol-required assessments may be
permitted after consultation with the participant, investigator, and the sponsor. Missed
assessments/visits will be captured in the clinical trial management system for protocol deviations.
Discontinuations of study interventions and withdrawal from the study should be documented with
the prefix “COVID-19-related” in the CRF.
If a participant has tested positive for COVID-19, the investigator should contact the sponsor’s
responsible medical officer to discuss plans for administration of study intervention, performing
study assessments, and follow-up. Modifications made to the study conduct as a result of the
COVID-19 pandemic should be summarized in the clinical study report.

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GUIDANCE SPECIFIC TO THIS PROTOCOL
Screening and Randomization
 Enrollment of new participants may continue based on the investigator’s assessment of risks
versus benefits, depending on the situation at a particular site, and the ability to monitor
participant safety.
Site Visits
 
When site visits are not possible due to local/national guidelines, sites should collect the
assessments via telephone visits or home-based visits, if the participant allows. The actual
visit date and the type of visit (ie, telephone or home-based visit) should be captured in the
eCRF according to the eCRF completion guidelines. Procedures that cannot be performed
during a home-based visit (eg, blood samples, and physical examination), should be excluded.
Vaccine Administration
 
When planning for vaccination visits, local/national or institutional guidelines will be
followed. The study vaccine must be administered by a blinded qualified individual at the
study site. If this is not possible, a solution may be considered in consultation with the sponsor
and taking into consideration participant safety.
Informed Consent Form
 
Consenting and re-consenting of participants for the measures taken (including also remote
consenting by phone or video consultation) will be performed as applicable and according to
local guidance for informed consent applicable during the COVID-19 pandemic. The process
is to be documented in the source documents.
Source Data Verification/Monitoring
 
In case on-site monitoring visits are not possible, the site monitor may contact the investigator
to arrange monitoring visits and activities remotely (in accordance with site and local
requirements). Additional on-site monitoring visits may be needed in the future to catch up on
source data verification.
Site Audits
 
During the COVID-19 pandemic and at the impacted sites, study site GCP audits with direct
impact/engagement from the investigator and study site personnel would not be conducted in
order to comply with national, local, and/or organizational social distancing restrictions.
Additional quality assurance activities such as remote audits or focused review of study-
related documents may take place with limited impact/engagement if possible.

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10.8. Appendix 8: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located
directly before the Table of Contents (TOC).
Amendment 1 (23 May 2022)
Overall Rationale for the Amendment: To include additional potential risks and adverse events of
special interest, and adjust study objectives, endpoints and enrollment criteria for study population.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1. Synopsis Objectives
and Endpoints; 1.1.
Synopsis Overall Design; 3.
Objectives and Endpoints;
4.1. Overall Design; 5.1.
Inclusion Criteria; 9.2.
Sample Size Determination
Age range for study participants was changed
from ≥18 to ≤39 years of age to ≥18 to ≤45
years of age.
This change of age range will
facilitate study enrollment and
does not impact assessment of
study objectives and endpoints
and does not impact participant
safety.
1.1. Synopsis Objectives
and Endpoints; 3.
Objectives and Endpoints
Changes on primary endpoints:
Specified that occurrence, severity, duration
and relationship of solicited and unsolicited
adverse events (AEs), and occurrence and
relationship of serious adverse events
(SAEs), will be assessed.
Added an additional endpoint to assess
occurrence and relationship of adverse events
of special interest (AESIs) from first
vaccination dose to 6 months after the second
vaccination dose.
Parameters on the AE and SAE
assessment were added for
clarification on safety analyses.
Assessment for AESI was added
based on inclusion of AESI in
newly added Section 8.3.6
Adverse Events of Special
Interest.
1.1. Synopsis Objectives
and Endpoints; 1.1.
Synopsis Table Summary of
Immunogenicity Assays; 3.
Objectives and Endpoints;
8.1. Immunogenicity
Assessments
Changes on secondary and exploratory
endpoints:
The functionality tests of antibodies binding
to the stem or the full-length HA protein was
moved from secondary endpoint to
exploratory endpoint.
The timepoints for secondary endpoint
assessment were removed.
Memory B cell response was added as an
exploratory endpoint.
The exploratory endpoint for nasal targeting
of the antibody response was removed.
Removed based on change of
study vaccine development
strategy per the sponsor.
Removed as the magnitude tests
will be completed for all
timepoints listed in Section 1.3
Schedule of Activities.
Added based on the sponsor’s
assessment on assay requirement
for decision-making.
Removed based on the sponsor’s
assessment on assay requirement
for decision-making.
1.1. Synopsis Overall
Design; 2.3.3. Benefit-Risk
Assessment Related to
Study Vaccination; 4.1.
Overall Design; 6.3.3
Measures to Minimize Bias:
The following sentences were removed:
These sentinel participants will be enrolled at
the same site. These sentinel participants will
be dosed at least 1 hours apart. The
maximum number of sentinel participants to
be vaccinated on the same day should not
exceed 4.
Removed based on the sponsor’s
assessment on the updated safety
data of adenovirus 26 (Ad26)-
vectored vaccines.

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Section Number 
and Name
Description of Change 
Brief Rationale
Randomization and
Blinding
1.1. Synopsis Overall 
Design; 4.1. Overall 
Design; 6.3.3 Measures to 
Minimize Bias: 
Randomization and 
Blinding 
The following language was added for all 3 
Cohorts: 
DRC review will be held to review available 
safety data of initial participants enrolled 
before these participants can receive the
second vaccination.
Added to clarify that DRC review
will be held before the initial
participants can receive the
second vaccination.
1.1. Synopsis Table: Study 
Design: 
VAC21148FLZ1001; 1.1. 
Synopsis First-dose Safety 
Cohort 1; 1.1. Synopsis 
First-dose Safety Cohort 2; 
1.1. Synopsis First-dose 
Safety Cohort 3; 1.1. 
Synopsis Number of 
Participants; 1.1. Synopsis 
Immunogenicity 
Evaluations; 1.3.1 Schedule 
of Activities –Assessments 
for All Participants; 4.1.
Overall Design; 6.3.
Measures to Minimize Bias:
Randomization and
Blinding; 8.1.
Immunogenicity
Assessments
Changes to the number of participants in 
certain Cohorts/Groups: 
Two participants from Group 4 (placebo) in 
Cohort 1 and Group 8 (placebo) in Cohort 2
were moved to Group 13 (placebo) in Cohort
3. In-depth immunogenicity subset was
changed from up to 5 participants per
regimen in Cohort 1 and 3 to up to 9
participants per regimen in Cohort 3 (9
subjects in Group 9-12 and 6 subjects in
Group 13). The number of total participants
for Cohort 1, 2 and 3 was changed from 52,
28, and 90 to 50, 26 and 94, respectively.
Modified based on the sponsor’s
assessment on data requirement
to support regimen selection.
1.1. Synopsis Study 
Vaccine; 6.1. Study 
Vaccine(s) Administered; 
6.4. Study Vaccine 
Compliance 
Language was added that instructions on 
study vaccine preparation (eg, dilution in
formulation buffer) into the final dose that
participants receive within each treatment
group are outlined in detail in the
Investigational Product Preparation
Instructions.
Language added to allow alternative location 
for study vaccine injection if an injection 
cannot be given in the deltoids due to a 
medical or other contraindication.
Added for clarification.
Added to allow alternative
location for study vaccine
injection.
1.1. Synopsis 
Immunogenicity 
Evaluations; 1.3.1. Schedule 
of Activities –Assessments
for All Participants; 4.1
Overall Design; 8.1.
Immunogenicity
Assessments;
Nasosorption, PAXGene, and proteome 
stabilization sample collection and analysis 
were removed. 
Removed based on the sponsor’s
assessment on data requirement
to support decision-making.
1.1. Synopsis ILI 
Procedures; 1.3.2. Schedule 
of Activities –Assessments 
for Participants With 
Influenza-Like Illness (ILI); 
8.1.1. ILI Procedures; 
One additional activity for Days 3-5 was 
added for reverse transcriptase polymerase 
chain reaction (RT-PCR) diagnostics and/or 
rapid-PCR detection for influenza virus 
infection on collected nasal swab samples on 
Days 1-2 and Days 3-5, which should be 
completed by qualified site staff.
Added to clarify that RT-PCR
diagnostics and/or rapid-PCR
detection for influenza virus
infection on collected nasal swab
samples will be completed by
sites.

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Section Number 
and Name
Description of Change 
Brief Rationale
ILI form was added for participants to 
complete daily from onset of ILI to 
resolution. 
One additional activity for Days 3-5 and Day 
29 was added for site staff to collect and
review completed Flu-iiQTM questionnaire
and ILI form.
Added to clarify the
documentation for temperature
measured daily.
Added to clarification.
1.1. Synopsis ILI 
Procedures; 1.3.2. Schedule 
of Activities –Assessments 
for Participants With 
Influenza-like Illness (ILI) 
8.1.1. ILI Procedures; 8.3.1. 
Time Period and Frequency 
for Collecting Adverse 
Event and Serious Adverse 
Event Information; 10.4. 
Appendix 4: Adverse
Events: Definitions and
Procedures for Reporting,
Evaluating, Follow-up, and
Reporting
Requirements on AE reporting for ILI 
with/out influenza virus infection were 
revised: Any ILI and complications related to
ILIs will be reported as an AE if it occurs
between the time of any vaccination through
the following 28 days. An ILI and
complications related to ILIs that occur
outside of this period does not require AE
reporting unless ongoing at the time of
subsequent vaccination.
Modified for consistent AE
reporting.
1.1. Synopsis ILI 
Procedures; 8.1.1. ILI 
Procedures; 10.4. Appendix 
4: Adverse Events: 
Definitions and Procedures 
for Reporting, Evaluating,
Follow-up, and Reporting
SAE downgrading for ILI with a positive 
RT-PCR test for influenza virus is no longer 
allowed. Any ILI and complications related
to ILIs fulfilling the criteria of an SAE will
be reported as such.
Modified for consistent SAE
reporting criteria and process.
1.1. Synopsis Safety 
Evaluations; 1.3.1. Schedule 
of Activities –Assessments 
for All Participants; 4.1. 
Overall Design; 8.3.1. Time
Period and Frequency for
Collecting Adverse Event
and Serious Adverse Event
Information
The monitoring duration for AESIs was 
added from the day of first vaccination until 
6 months after second vaccination. 
Added based on inclusion of
primary endpoint for AESI in
Section 3 Objectives and
Endpoints.
1.1. Synopsis Populations 
for Analyses; 9.3. 
Populations for Analyses 
Enrolled population for analyses was 
removed. 
Removed based on the sponsor’s
assessment on the analyses
required.
1.1. Synopsis Planned 
Analyses; 9.5. Planned 
Analyses 
Blinded interim analysis was removed. 
Language was added to allow additional 
interim analysis if needed. 
Language added that only immunogenicity 
data on quantification of antibody binding to
full-length hemagglutinin (HA) up to the 28
days post-dose 2 visit are required for the
primary analysis, in addition to safety data.
Blinded interim analysis is no
longer required. The study data
will be analyzed in the planned
primary analysis instead.
Additional interim analysis may
be performed if needed.
Added for clarification.

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Section Number 
and Name
Description of Change 
Brief Rationale
1.2. Schema; 1.3.1 Schedule 
of Activities –Assessments 
for All Participants; 4.1. 
Overall Design; 5.1. 
Inclusion Criteria; 8. Study 
Assessments and 
Procedures Table 2 
Language to allow Screening visit and Day 1 
visit to occur on the same day was removed, 
and Figure 1 was updated accordingly. 
The investigator will need to
review clinical safety laboratory
results from the Screening visit to
determine participant eligibility,
which was added as a new
inclusion criterion #10 in Section
5.1 Inclusion Criteria.
Considering the time required to
receive and review laboratory
results by the sites, it is not
possible to have the Screening
visit and Day 1 visit on the same
day.
1.3.1. Schedule of Activities 
–Assessments for All 
Participants 
Physical examination was added for Day 1 
and Day 57 visits. AESI recording and 
clinical safety laboratory tests were added. 
Blood volume was adjusted to include 
clinical safety laboratory tests. Footnote i 
was added for blood sample collection.
Urine pregnancy test at screening visit was 
changed to serum pregnancy test. 
Updated footnote g to include additional 
inclusion criteria 6 and exclusion criteria 21, 
22, 23 and 24. 
Footnote n was added that ruler and 
thermometers will be distributed at Day 1
visit, and training will be conducted by the
site staff at both Day 1 and Day 57 visits.
Additional safety measurements
are added to be aligned with other
Ad26-based vaccine studies and
the updates in the Investigator
Brochure.
Modified to include a more
sensitive pregnancy test for
screening visit.
Updated based on updated
inclusion and exclusion criteria in
Section 5 Study Population of the
amendment.
Added for clarification.
1.3.2. Schedule of Activities 
–Assessments for 
Participants With Influenza- 
Like Illness (ILI) 
Language was added that nasal swab samples 
collected by the participant at home on Days
1-2 should be delivered to site staff on Days
3-5.
Added for clarification.
2. Introduction; 2.3.1. Risks 
Related to Study 
Vaccination  
Safety data supporting dose selection for 
study vaccines were updated, and new risks 
related to Ad26-vectored vaccines were 
added. 
Included new safety data and
risks from clinical studies for
other Ad26-based vaccines that
have become available after the
original protocol finalization in
January 2020.
2.2.1. Nonclinical Studies 
Language on nonclinical experience with 
Ad26-based vaccines using various transgene 
inserts are removed. 
Language was added that genotoxicity and 
carcinogenicity studies have not been 
performed and the components of the study
Removed as the clinical
experience with Ad26-based
vaccines using various transgene
inserts have been included in
Section 2 Introduction and
Section 2.3.1. Risks Related to
Study Vaccination, and therefore
supersede the nonclinical data.
Added based on the Investigator
Brochure v2.0.

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Section Number 
and Name
Description of Change 
Brief Rationale
vaccine are not expected to have genotoxic or
carcinogenic potential.
2.3.1. Risks Related to 
Study Vaccination; 8.3.5. 
Pregnancy  
Language added to follow up the outcome of 
pregnancy for the partner of a male 
participant who becomes pregnant during the 
study and consents for the follow-up.
Added to ensure safety follow-up
for the partner of a male
participant in case of pregnancy.
2.3.1. Risks Related to 
Study Vaccination 
Risks related to concomitant vaccination 
were added. 
Included to clarify potential risks
with concomitant vaccination.
2.3.3. Benefit-Risk 
Assessment Related to 
Study Vaccination 
AESI was added as part of safety monitoring 
for the study. 
Added based on inclusion of
AESI in newly added Section
8.3.6 Adverse Events of Special
Interest.
4.1. Overall Design; 6.3. 
Measures to Minimize Bias: 
Randomization and 
Blinding 
The following language was removed: 
These in-depth immunogenicity participants 
will be enrolled at the same site. 
Removed based on process
change on sample collection and
processing for peripheral blood
mononuclear cells by the sponsor.
4.1. Overall Design; 8.2.3. 
Clinical Safety Laboratory 
Assessment; 10.6. Appendix 
6: Clinical Laboratory Tests
Clinical safety laboratory assessments were 
added. 
Added to provide investigators
additional safety parameters for
eligibility and safety assessment.
4.1. Overall Design; 8.1.1. 
ILI Procedures; 10.6. 
Appendix 6: Clinical 
Laboratory Tests 
The presence of influenza virus infection will 
be assessed by qualified site staff on the nasal 
swab samples, instead of by the sponsor. The
test may be repeated at a central lab upon
sponsor request.
Updated based on change of
study operation plan.
4.2.1. Study-Specific 
Ethical Design  
Considerations 
The Belgian Red Cross guidelines on the 
volume for blood collection was updated 
from 450-470 mL up to 4 times a year to 
430-470ml up to 4 times a year.
Updated based on updated
information in Belgian Red Cross
websites.
5.1. Inclusion Criteria 
Inclusion criterion#4. A note was added to 
ensure that a participant must be healthy per
the investigator’s judgement prior to study
vaccine administration on Day 1 and Day 57.
Inclusion criterion #5. Male or female 
condom with or without spermicide was 
removed from the list of highly effective 
contraception methods. 
Inclusion criterion #6. The criterion was 
modified to have a negative highly sensitive 
serum pregnancy test at screening. 
Inclusion criterion #10. New inclusion 
criterion was added that participant must be 
healthy on the basis of clinical laboratory 
tests performed at screening. 
Added for clarification.
Male or female condom with or
without spermicide is no longer
considered as a highly effective
contraception method.
Modified based on the change in
Section 1.3.1 Schedule of
Activities –Assessment for all
Participants.
Added based on inclusion of
clinical safety laboratory tests in
Section 1.3 Schedule of Activities
and Section 8.2.3 Clinical Safety
Laboratory Assessments of the
amendment.
5.2. Exclusion Criteria 
Exclusion criterion #4. Criterion was updated 
to exclude participants with history of severe 
Updated based on changes in
Investigator Brochure.

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Section Number 
and Name
Description of Change 
Brief Rationale
allergic reaction (eg, anaphylaxis) to any
component of the study vaccines or severe
allergic reaction after a dose of any other
adenovirus-based vaccine.
Exclusion criterion #5. Further details were 
added for expectation on abnormal function 
of immune system.
Exclusion criterion #6. History of chronic 
idiopathic demyelinating polyneuropathy was 
added as an exclusion criterion. 
Exclusion criterion #9. Day 365 was 
removed as an indication for the end of the 
study.
Exclusion criterion #10. Participation in an 
observational clinical study is no longer 
allowed during the course of the study.
Exclusion criterion #12. The following 
criterion was added: Oocyte donation is 
prohibited while enrolled in this study.
Exclusion criterion #14. Participate has major 
surgery planned during the study duration are 
excluded. The requirement ‘within 6 months 
after the last dose of study vaccine
administration’ was removed.
Exclusion criterion #22. New exclusion 
criterion was added to exclude participants 
with history of thrombocytopenia, 
thrombosis with thrombocytopenia syndrome
(TTS), immune thrombocytopenic purpura,
or heparin-induced thrombocytopenia with
thrombosis.
Exclusion criterion #23. New exclusion 
criterion was added to exclude participants 
who receive or plan to receive an Ad26- 
vectored vaccine. 
Exclusion criterion #24. New exclusion 
criterion was added to exclude participants 
who have taken any disallowed therapies 
noted in Section 6.5 Concomitant Therapy.
Further details were added to
clarify the expectation.
Added based on new risks
included in Investigator Brochure
and the amendment.
Minor edit made to avoid
confusion.
Modified in consideration of
participant safety.
Added to clarify requirement for
oocyte donation.
Modified to clarify that the
requirement applies for the entire
study duration.
Added based on new risks
included in Investigator Brochure
and the amendment.
Added due to possible induction
of anti-Ad26 antibody in
participants with previous
exposure to Ad26-vectored
vaccines, which may impact
study endpoint analysis.
Added to ensure that the
requirements of prohibited
medications are met.

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Section Number 
and Name
Description of Change 
Brief Rationale
Language was added that the clinical 
laboratory results on Day 1 and Day 57 are
not required for eligibility assessment.
Added for clarification.
6.3. Measures to Minimize 
Bias: Randomization and 
Blinding 
Cohort and site were removed as 
stratification factors. 
Language added that the randomization 
codes will be disclosed if required for an 
interim analysis. 
Adjusted based on the change of
randomization and enrollment
plan per the sponsor.
Added to allow randomization
code disclosure for interim
analysis if required.
6.5. Concomitant Therapy  
Language added that Ad26-vectored vaccines 
are not allowed at any time prior to 
randomization until 28 days after the last 
study vaccination. 
Prohibited chronic or recurrent use of 
systemic corticosteroids was changed from 6 
months to 2 months before administration of 
study vaccine until the end of the study.
Radiotherapy was added as an example for 
immunomodulators/suppressors and
prohibited from 6 months before the first
study vaccination until the end of the study.
Added due to possible induction
of anti-Ad26 antibody in
participants with previous
exposure to Ad26-vectored
vaccines, which may impact
study endpoint analysis.
Modified in consideration of
short half-life of systemic
corticosteroids.
Added for clarification.
6.8. Study Pausing Rules 
Language was modified that further 
vaccination of participants may (instead of
will) be paused after medical review as
described.
AESIs and laboratory abnormality were 
added in study pausing rules. 
Modified for clarification.
Added based on inclusion of
Clinical safety laboratory
assessments in newly added
Section 8.2.3. Clinical Safety
Laboratory Assessment and
inclusion of AESI in newly added
Section 8.3.6 Adverse Events of
Special Interest.
6.8. Study Pausing Rules; 
8.3.1. Time Period and 
Frequency for Collecting 
Adverse Event and Serious
Adverse Event Information;
10.4. Appendix 4: Adverse
Events: Definitions and
Procedures for Reporting,
Evaluating, Follow-up, and 
Reporting
Transmission method for SAE form was 
updated from fax or email to a secure manner 
electronically or by fax to the sponsor. 
Transmission method for AESI form was 
added via a secure manner electronically or 
by fax to the sponsor. 
Modified based on change of
safety reporting process per the
sponsor.
Added based on inclusion of
AESI in newly added Section
8.3.6 Adverse Events of Special
Interest.
7.1. Discontinuation of 
Study Vaccine 
Study vaccine related confirmed TTS, and 
safety reasons and reactogenicity reasons 
Added based on inclusion of
AESI in newly added Section

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Section Number 
and Name
Description of Change 
Brief Rationale
were added to the list of criteria for 
discontinuation of study vaccine in 
participants. 
8.3.6 Adverse Events of Special
Interest and consideration for
participant safety.
7.1.1. Criteria for 
Temporarily Delaying 
Study Vaccine 
Administration 
Medically indicated vaccinations was added 
as one of the criteria for temporarily delaying 
study vaccine administration. 
Added in consideration of new
risks included for concomitant
vaccination in Section 2.3.1 of the
amendment.
7.2. Participant 
Discontinuation/Withdrawal 
From the Study  
AE that requires discontinuation from the 
study was added as one of the reasons to 
withdraw participants from the study.
Added in consideration of
participant safety.
8. Study Assessments and 
Procedures 
Blood volume was updated to include clinical 
safety laboratory assessments. 
Updated based on changes in
Section 1.3 Schedule of Activities
of the amendment
8.1. Immunogenicity 
Assessments 
Language added to allow immunogenicity 
samples to be used for safety assessment. 
Added in consideration of
participant safety.
8.3.1. Time Period and 
Frequency for Collecting 
Adverse Event and Serious 
Adverse Event Information  
Language below was added: 
All AEs of Grade 3 or above must be 
reported to the appropriate sponsor contact 
person by study-site personnel within
24 hours of their knowledge of the event.
Relevant AE information should be updated
in the eCRF on the same day when the AE
information is collected (see Section 6.8
Study Pausing Rules).
Added to be consistent on the AE
reporting requirement based on
Section 6.8 Study Pausing Rules.
8.3.2. Method of Detecting 
Adverse Events and Serious 
Adverse Events
Text regarding transcription of participant 
diary entries into the eCRF was updated. 
Modified to clarify the
expectation and process.
8.2.4. Pregnancy Testing 
New section added 
Added to provide further
expectation and details for
pregnancy testing.
8.3. Adverse Events, 
Serious Adverse Events, 
Adverse Events of Special
Interest, and Other Safety
Reporting
Section title was updated to include AESI 
and other safety reporting. 
Updated based on changes made
in this section of the amendment.
8.3.1. Time Period and 
Frequency for Collecting 
Adverse Event and Serious 
Adverse Event Information;
8.3.6. Adverse Events of
Special Interest; 8.4.
Treatment of Overdose;
10.4. Appendix 4: Adverse
Events: Definitions and
Procedures for Reporting,
Evaluating, Follow-up, and
Reporting; 10.7. Appendix
7: Thrombotic Events to be
Recorded as AESIs
Details for AESI were added. 
Added based on new risks and
AESI included in Investigator
Brochure and the amendment.
8.3.3. Follow-up of Adverse 
Events and Serious Adverse 
Events 
Language added for the investigators to 
perform or arrange for the conduct of 
supplemental measurements and evaluations
as medically indicated.
Added to clarify the
investigators’ responsibilities.

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Section Number 
and Name
Description of Change 
Brief Rationale
9.4. Statistical Analyses 
Language added to create a separate analysis 
plan to support DRC meeting.
Added for clarification.
9.4.2. Primary Endpoint(s) 
AESI was added for primary endpoints. 
Summary language added to include vital 
signs, physical examination and clinical 
safety laboratory assessments for safety 
assessment, and more detailed description for 
vital signs and Physical Examinations are
removed.
Added based on change of
primary endpoints in Section 3
Objectives and Endpoints of the
amendment.
Modified to clarify the additional
safety analyses in addition to the
primary endpoints listed for
safety assessment.
10.1. Appendix 1: 
Abbreviations 
Abbreviations were updated. 
Updated based on changes in the
amendment.
10.3. Appendix 3: 
Regulatory, Ethical, and 
Study Oversight
Considerations 
Language for use of Protocol Clarification 
Communications was added. 
Language added to allow remote consenting 
per local regulations. 
Language added on how the sponsor handles 
an event of a data security breach. 
AESI was added for data review by Data 
Review Committee. 
Added based on process change
per the sponsor.
Added to allow flexibility on
consenting method for
participants and site staff.
Added to clarify expectation in
case of a data security breach.
Added based on inclusion of
AESI in Section 8.3.6 Adverse
Event of Special Interest of the
amendment.
10.4. Appendix 4: Adverse 
Events: Definitions and 
Procedures for Reporting, 
Evaluating, Follow-up, and
Reporting
Reporting of participant pregnancy or 
participant partner(s) pregnancy was added 
as one of special reporting situations.
Added based on reporting
requirement per the sponsor.
10.5. Appendix 5: Toxicity 
Grading Scale 
Table B was added for laboratory 
abnormalities. 
Added to provide guidance on
assessment of clinical laboratory
tests included in Appendix 6
Clinical Laboratory Tests and
Section 8.3.6 Adverse Events of
Special Interest added as part of
this amendment, as well as other
laboratory tests performed based
on the investigator’s judgment.
10.8. Appendix 8: Study 
Conduct During a Pandemic 
New section added. 
Added to clarify expectation on
study conduct during Coronavirus
Disease 2019 pandemic.
10.9. Appendix 9: Protocol 
Amendment History  
Language updated to reference protocol 
amendment summary of changes table before 
the Table of Contents.
Updated to reflect amendment
history.
11. References 
New references added and reference format 
updated throughout the protocol amendment. 
Updated based on review of
references by the sponsor
Investigator Agreement 
Sponsor’s responsible medical officer was 
changed from Jerald Sadoff to Bridgette 
Franey.
Changed based on the sponsor
team change

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Section Number 
and Name
Description of Change 
Brief Rationale
Throughout the protocol 
Minor language updates were made for 
consistency and clarification. 
Minor language updates made
throughout the protocol to clarify
and be consistent with the
changes noted in the sections
listed above.
Throughout the protocol 
Minor grammatical, formatting, or spelling 
changes were made.
Minor errors were noted.

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11. 
REFERENCES
Ameratunga R, Gillis D, Gold M, Linneberg A, Elwood JM. Evidence Refuting the Existence of
Autoimmune/Autoinflammatory Syndrome Induced by Adjuvants (ASIA). J Allergy Clin Immunol Pract.
2017;5(6):1551-1555.e1.
Baylor NW, Egan W, Richman P. Aluminum salts in vaccines--US perspective. Vaccine. 2002;20 Suppl 3:S18-23.
Bergfors E, Trollfors B, Inerot A. Unexpectedly high incidence of persistent itching nodules and delayed
hypersensitivity to aluminium in children after the use of adsorbed vaccines from a single manufacturer. Vaccine.
2003;22(1):64-69.
Bergfors E, Hermansson G, Nyström Kronander U, Falk L, Valter L, Trollfors B. How common are long-lasting,
intensely itching vaccination granulomas and contact allergy to aluminium induced by currently used pediatric
vaccines? A prospective cohort study. Eur J Pediatr. 2014;173(10): 1297–1307.
Centers for Disease Control and Prevention (CDC). Estimates of deaths associated with seasonal influenza ---
United States, 1976-2007. MMWR Morb Mortal Wkly Rep. 2010;59(33):1057-1062.
https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5933a1.htm. Accessed 4 March 2022.
Centers for Disease Control and Prevention (CDC). Seasonal influenza-associated hospitalizations in the United
States. https://www.cdc.gov/flu/about/burden/faq.htm (last updated: 21 October 2021). Accessed 4 March 2022.
Cox MM, Izikson R, Post P, Dunkle L. Safety, efficacy, and immunogenicity of Flublok in the prevention of
seasonal influenza in adults. Ther Adv Vaccines. 2015;3(4):97-108.
Diazgranados CA, Dunning AJ, Kimmel M, et al. Efficacy of high-dose versus standard-dose influenza vaccine in
older adults. N Engl J Med. 2014;371(7):635-645.
Eickhoff TC, Myers M. Workshop summary. Aluminum in vaccines. Vaccine. 2002;20 Suppl 3:S1-4.
Gidudu JK, Walco GA, Taddio A, et al./The Brighton Immunization Site Pain Working Group. Immunization site
pain: Case definition and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine.
2012:30;4558-4577.
Grohskopf LA, Alyanak E, Broder KR, Walter EB, Fry AM, Jernigan DB. Prevention and Control of Seasonal
Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States,
2019-20 Influenza Season. MMWR Recomm Rep. 2019;68(3):1-21.
Jefferson T, Rudin M, Di pietrantonj C. Adverse events after immunisation with aluminium-containing DTP
vaccines: systematic review of the evidence. Lancet Infect Dis. 2004;4(2):84-90.
Keith LS, Jones DE, Chou CH. Aluminum toxicokinetics regarding infant diet and vaccinations. Vaccine. 2002;20
Suppl 3:S13-17.
Kohl KS, Walop W, Gidudu J, et al./The Brighton Collaboration Local Reaction Working Group for Swelling at or
near Injection Site. Swelling at or near injection site: Case definition and guidelines for collection, analysis and
presentation of immunization safety data. Vaccine 2007:31;5858-5874
Marcy SM, Kohl KS, Dagan R, et al./The Brighton Collaboration Fever Working Group. Fever as an adverse event
following immunization: case definition and guidelines of data collection, analysis, and presentation. Vaccine
2004:22;551-556.
Milligan ID, Gibani MM, Sewell R, et al. Safety and immunogenicity of novel adenovirus type 26- and modified
vaccinia ankara-vectored ebola vaccines: a randomized clinical trial. JAMA. 2016:315;1610-1623.
Mitkus RJ, King DB, Hess MA, Forshee RA, Walderhaug MO. Updated aluminum pharmacokinetics following
infant exposures through diet and vaccination. Vaccine. 2011;29(51):9538-9543.
Netterlid E, Bruze M, Hindsén M, Isaksson M, Olin P. Persistent itching nodules after the fourth dose of diphtheria-
tetanus toxoid vaccines without evidence of delayed hypersensitivity to aluminium. Vaccine. 2004;22(27-28):3698-
3706.
Tan HX, Jegaskanda S, Juno JA, et al. Subdominance and poor intrinsic immunogenicity limit humoral immunity
targeting influenza HA stem. J Clin Invest. 2019;129(2):850-862.

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Treanor JJ, El sahly H, King J, et al. Protective efficacy of a trivalent recombinant hemagglutinin protein vaccine
(FluBlok®) against influenza in healthy adults: a randomized, placebo-controlled trial. Vaccine. 2011;29(44):7733-
7739.
Treanor JJ, Schiff GM, Hayden FG, et al. Safety and immunogenicity of a baculovirus-expressed hemagglutinin
influenza vaccine: a randomized controlled trial. JAMA. 2007;297(14):1577-1582.
U.S. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation
and Research. September 2007. Guidance for Industry. Toxicity Grading Scale for Healthy Adult and Adolescent
Volunteers Enrolled in Preventive Vaccine Clinical Trials. Available at:
https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/V
accines/ucm091977.pdf. Accessed: 05 May 2022.
US Department of Health and Human Services. Office for Human Research Protections - OHRP Expedited Review
Categories (1998). Available at: http://www.hhs.gov/ohrp/regulations-and-policy/guidance/categories-of-research-
expedited-review-procedure-1998/index.html. Accessed 06 February 2022.
US Food and Drug Administration. Conditions for IRB Use of Expedited Review. Federal Register: November 9,
1998 (Volume 63, Number 216). Available at: https://www.hhs.gov/ohrp/news/federal-register-notices/federal-
register-11-09-1998-vol-63-no-216/index.html. Accessed 06 February 2022.
World Health Organization (WHO). Influenza (Seasonal). 6 November 2018. https://www.who.int/en/news-
room/fact-sheets/detail/influenza-(seasonal). Accessed 4 March 2022.
World Health Organization. WHO guidelines on nonclinical evaluation of vaccines. WHO Technical Report Series,
No. 927, Annex 1. 2005. Available at: https://www.who.int/publications/m/item/annex1-nonclinical.p31-63.
Accessed 17 April 2022.

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INVESTIGATOR AGREEMENT
I have read this protocol and agree that it contains all necessary details for carrying out this study. I will
conduct the study as outlined herein and will complete the study within the time designated.
I will provide copies of the protocol and all pertinent information to all individuals responsible to me who
assist in the conduct of this study. I will discuss this material with them to ensure that they are fully informed
regarding the study intervention, the conduct of the study, and the obligations of confidentiality.
Coordinating Investigator (where required):
Name (typed or printed):
Institution and Address:
Signature: 
Date:
(Day Month Year)
Principal (Site) Investigator:
Name (typed or printed):
Institution and Address:
Telephone Number:
Signature: 
Date:
(Day Month Year)
Sponsor's Responsible Medical Officer:
Name (typed or printed): 
Institution: 
Janssen Research & Development
Signature: electronic signature appended at the end of the protocol 
Date:
(Day Month Year)
Note: If the address or telephone number of the investigator changes during the study, written notification will be
provided by the investigator to the sponsor, and a protocol amendment will not be required.
PPD

Signature
User 
Date 
Reason
02-Mar-2023
20:09:50
(GMT)
Document Approval
PPD