A Phase 3 Randomized Double-blind Controlled Study to Evaluate the Immunogenicity, Safety, and Reactogenicity of ExPEC9V and High-dose Quadrivalent Influenza Vaccine, With and Without Co-administration, in Adults Aged 65 Years or Older
Phase: PHASE3
Conditions: Invasive Extraintestinal Pathogenic Escherichia Coli Disease (IED) Prevention
Sponsor: Janssen Research & Development, LLC

CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
1
Status: Approved, Date: 22 September 2023
Janssen Research & Development*
Clinical Protocol
A Phase 3 Randomized Double-blind Controlled Study to Evaluate the Immunogenicity,
Safety, and Reactogenicity of ExPEC9V and High-dose Quadrivalent Influenza Vaccine,
With and Without Co-administration, in Adults Aged 65 Years or Older
E.ngage
Protocol VAC52416BAC3002; Phase 3
Version: Amendment 1
VAC52416 (JNJ-78901563) ExPEC9V
*Janssen Research & Development is a global organization that operates through different legal entities in
various countries/territories. Therefore, the legal entity acting as the sponsor for Janssen Research &
Development studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP;
Janssen Biologics, BV; Janssen-Cilag International NV; Janssen, Inc; Janssen Pharmaceutica NV; Janssen
Sciences Ireland UC; Janssen Biopharma Inc., or Janssen Research & Development, LLC. The term
“sponsor” is used throughout the protocol to represent these various legal entities; the sponsor is identified
on the Contact Information page that accompanies the protocol.
United States (US) sites of this study will be conducted under US Food & Drug Administration
Investigational New Drug (IND) regulations (21 CFR Part 312).
Regulatory Agency Identifier Number(s)
Registry  
ID
EU TRIAL NUMBER
2023-504168-40-00
Status: 
Approved
Document Date: 
22 September 2023
Prepared by: 
Janssen Vaccines & Prevention B.V.
EDMS Number: 
EDMS-RIM-914860; 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.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
2
Status: Approved, Date: 22 September 2023
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document 
Country/Territory Affected  
Date
Amendment 1 
All 
22 September 2023
Original Protocol 
All 
22 February 2023
Amendment 1 (22 September 2023)
Overall Rationale for the Amendment: The main purpose of this amendment is to add an Independent
Data Monitoring Committee (IDMC) and mandate the collection of medically-attended adverse events
(MAAEs) throughout the study.
The changes made to the clinical protocol VAC52416BAC3002 as part of Protocol Amendment 1 are listed
below, including the rationale of each change and a list of all applicable sections.
Section number 
and Name
Description of Change 
Brief Rationale
Title page
1.1 Synopsis
“EudraCT” was corrected to “EU
TRIAL number”.
Correction.
1.1 Synopsis
1.3 Schedule of Activities (SoA)
2.3.3 Benefit-risk Assessment of
Study Participation
3 OBJECTIVES AND ENDPOINTS
4.1 Overall Design
6.7 Treatment of Overdose
6.8 Concomitant Therapy
7.1 Discontinuation of Study
Vaccination
8.2 Safety Assessments
8.3 Adverse Events, Serious Adverse
Events, Medically-attended Adverse
Events, and Other Safety Reporting
9.4.4 Safety Analyses
10.2.10 Source Documents
10.3 Appendix 3: Adverse Events,
Serious Adverse Events,
Medically-attended Adverse Events,
Product Quality Complaints, and
Other Safety Reporting: Definitions
and Procedures for Recording,
Evaluating, Follow-up, and Reporting
The assessment of MAAEs was
added.
Added based on Health Authority
request.
1.1 Synopsis
2.3.3 Benefit-risk Assessment of
Study Participation
4.1 Overall Design
9.6 Independent Data Monitoring
Committee
10.2.6 Committees Structure
Description of the details and type
of data to be reviewed by the
Independent Data Monitoring
Committee (IDMC) was added.
Added based on Health Authority
request.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
3
Status: Approved, Date: 22 September 2023
Section number 
and Name
Description of Change 
Brief Rationale
2.3 Benefit-risk Assessment 
6.8 Concomitant Therapy  
Updated the paragraphs on 
allowed vaccines. 
For consistency in the ExPEC
programs.
5.4 Screen Failures 
The sentences “This study will 
use IWRS. The investigator will
generate screening and enrollment
logs directly from IWRS.” were
added.
Per Health Authority request.
10.2.10 Source Documents 
“Respiratory rate” was added to 
the list of data to be recorded 
directly into the eCRF.
Correction, to align with overall
vital signs assessments.
10.5 Appendix 5: Toxicity Grading 
Scale 
Toxicity Grading Scale for 
Platelets Decreased were updated.
Clarification.
Throughout the protocol 
Minor grammatical, formatting, or 
spelling changes were made.
Minor errors were noted
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
4
Status: Approved, Date: 22 September 2023
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 4
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 6
1. 
PROTOCOL SUMMARY..................................................................................................................... 7
1.1. 
Synopsis........................................................................................................................................... 7
1.2. 
Schema.......................................................................................................................................... 15
1.3. 
Schedule of Activities (SoA)........................................................................................................... 16
2. 
INTRODUCTION................................................................................................................................ 19
2.1. 
Study Rationale.............................................................................................................................. 19
2.2. 
Background.................................................................................................................................... 20
2.2.1. 
Seasonal Influenza Vaccine ....................................................................................................... 22
2.3. 
Benefit-risk Assessment................................................................................................................. 22
2.3.1. 
Risks Related to Study Participation .......................................................................................... 22
2.3.2. 
Benefits of Study Participation.................................................................................................... 24
2.3.3. 
Benefit-risk Assessment of Study Participation.......................................................................... 24
3. 
OBJECTIVES AND ENDPOINTS ..................................................................................................... 25
4. 
STUDY DESIGN ................................................................................................................................ 28
4.1. 
Overall Design................................................................................................................................ 28
4.2. 
Scientific Rationale for Study Design............................................................................................. 29
4.2.1. 
Study-specific Ethical Design Considerations ............................................................................ 29
4.3. 
Justification for Dose...................................................................................................................... 30
4.4. 
End of Study Definition................................................................................................................... 30
5. 
STUDY POPULATION ...................................................................................................................... 30
5.1. 
Inclusion Criteria............................................................................................................................ 31
5.2. 
Exclusion Criteria........................................................................................................................... 32
5.3. 
Lifestyle Considerations................................................................................................................. 34
5.4. 
Screen Failures.............................................................................................................................. 35
5.5. 
Criteria for Temporarily Delaying Study Vaccine Administration ................................................... 35
6. 
STUDY VACCINATIONS AND CONCOMITANT THERAPY........................................................... 36
6.1. 
Study Vaccinations Administered .................................................................................................. 36
6.2. 
Preparation/Handling/Storage/Accountability ................................................................................ 38
6.3. 
Measures to Minimize Bias: Randomization and Blinding............................................................. 39
6.4. 
Study Vaccination Compliance ...................................................................................................... 40
6.5. 
Dose Modification........................................................................................................................... 40
6.6. 
Continued Access to Study Vaccination After the End of the Study.............................................. 40
6.7. 
Treatment of Overdose .................................................................................................................. 40
6.8. 
Concomitant Therapy..................................................................................................................... 41
7. 
DISCONTINUATION OF STUDY VACCINATION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL............................................................................................... 42
7.1. 
Discontinuation of Study Vaccination............................................................................................. 42
7.2. 
Participant Discontinuation/Withdrawal From the Study................................................................ 43
7.2.1. 
Withdrawal From the Use of Research Samples ....................................................................... 43
7.3. 
Lost to Follow up............................................................................................................................ 43
8. 
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 44
8.1. 
Immunogenicity Assessments ....................................................................................................... 46
8.2. 
Safety Assessments....................................................................................................................... 46
8.2.1. 
Physical Examinations................................................................................................................ 47
8.2.2. 
Vital Signs................................................................................................................................... 47
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
5
Status: Approved, Date: 22 September 2023
8.3. 
Adverse Events, Serious Adverse Events, Medically-attended Adverse Events, and Other
Safety Reporting ............................................................................................................................ 47
8.3.1. 
Time Period and Frequency for Collecting Adverse Event, Medically-attended Adverse
Events, and Serious Adverse Event Information........................................................................ 48
8.3.2. 
Method of Detecting Adverse Events, Medically-attended Adverse Events, and Serious
Adverse Events........................................................................................................................... 49
8.3.3. 
Follow-up of Adverse Events, Medically-attended Adverse Events, and Serious
Adverse Events........................................................................................................................... 50
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events ............................................. 50
8.3.5. 
Pregnancy................................................................................................................................... 51
8.4. 
Pharmacokinetics........................................................................................................................... 51
8.5. 
Genetics and Pharmacogenomics................................................................................................. 51
8.6. 
Biomarkers..................................................................................................................................... 51
8.7. 
Immunogenicity Assessments ....................................................................................................... 51
8.8. 
Medical Resource Utilization and Health Economics .................................................................... 51
9. 
STATISTICAL CONSIDERATIONS.................................................................................................. 51
9.1. 
Statistical Hypotheses.................................................................................................................... 51
9.2. 
Sample Size Determination ........................................................................................................... 52
9.3. 
Participant Analysis Sets................................................................................................................ 53
9.4. 
Statistical Analyses ........................................................................................................................ 54
9.4.1. 
General Considerations.............................................................................................................. 54
9.4.2. 
Participant Information................................................................................................................ 54
9.4.3. 
Immunogenicity Analyses........................................................................................................... 54
9.4.4. 
Safety Analyses.......................................................................................................................... 55
9.5. 
Interim Analysis.............................................................................................................................. 56
9.6. 
Independent Data Monitoring Committee ...................................................................................... 56
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............................ 57
10.1. 
Appendix 1: Abbreviations and Definitions .................................................................................... 57
10.2. 
Appendix 2: Regulatory, Ethical, and Study Oversight Considerations......................................... 59
10.2.1. 
Regulatory and Ethical Considerations ...................................................................................... 59
10.2.2. 
Financial Disclosure.................................................................................................................... 62
10.2.3. 
Informed Consent Process ......................................................................................................... 62
10.2.4. 
Data Protection ........................................................................................................................... 63
10.2.5. 
Long-term Retention of Samples for Additional Future Research.............................................. 64
10.2.6. 
Committees Structure................................................................................................................. 64
10.2.7. 
Publication Policy/Dissemination of Clinical Study Data............................................................ 64
10.2.8. 
Data Quality Assurance.............................................................................................................. 66
10.2.9. 
Case Report Form Completion................................................................................................... 66
10.2.10. Source Documents ..................................................................................................................... 66
10.2.11. Monitoring ................................................................................................................................... 67
10.2.12. On-site Audits ............................................................................................................................. 68
10.2.13. Record Retention........................................................................................................................ 68
10.2.14. Study and Site Start and Closure ............................................................................................... 69
10.3. 
Appendix 3: Adverse Events, Serious Adverse Events, Medically-attended Adverse
Events, Product Quality Complaints, and Other Safety Reporting: Definitions and
Procedures for Recording, Evaluating, Follow-up, and Reporting................................................. 70
10.3.1. 
Adverse Event Definitions and Classifications ........................................................................... 70
10.3.2. 
Attribution Definitions.................................................................................................................. 71
10.3.3. 
Severity Criteria.......................................................................................................................... 71
10.3.4. 
Special Reporting Situations ...................................................................................................... 72
10.3.5. 
Procedures ................................................................................................................................. 72
10.3.6. 
Product Quality Complaint Handling........................................................................................... 74
10.3.7. 
Contacting Sponsor Regarding Product Quality......................................................................... 74
10.4. 
Appendix 4: Contraceptive Guidance ............................................................................................ 75
10.5. 
Appendix 5: Toxicity Grading Scale............................................................................................... 76
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
6
Status: Approved, Date: 22 September 2023
10.6. 
Appendix 6: Specific Criteria for the Inclusion of Potential Participants with Chronic Stable
HIV, HCV, or HBV Infection ........................................................................................................... 80
10.7. 
Appendix 7: Protocol Amendment History..................................................................................... 81
11. REFERENCES................................................................................................................................... 82
INVESTIGATOR AGREEMENT................................................................................................................. 83
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Overview of the Groups, Targeted Number of Participants, and Vaccinations ........................ 28
FIGURES
Figure 1: Schematic Overview of the Study............................................................................................. 15
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
7
Status: Approved, Date: 22 September 2023
1. 
PROTOCOL SUMMARY
1.1. 
Synopsis
A Phase 3 Randomized Double-blind Controlled Study to Evaluate the Immunogenicity, Safety,
and Reactogenicity of ExPEC9V and High-dose Quadrivalent Influenza Vaccine, With and
Without Co-administration, in Adults Aged 65 Years or Older
Registry  
ID
EU TRIAL NUMBER  
2023-504168-40-00
DESCRIPTION OF COMPOUND
ExPEC9V (primary compound number: VAC52416) is a 9-valent vaccine candidate in development for
active immunization for the prevention of invasive extraintestinal pathogenic Escherichia coli (ExPEC)
disease (IED) in adults 60 years of age and older. ExPEC9V consists of the O-antigen polysaccharides
(PSs) of the ExPEC serotypes O1A, O2, O4, O6A, O15, O16, O18A, O25B, and O75 separately
bioconjugated to the carrier protein, a genetically detoxified form of exotoxin A derived from Pseudomonas
aeruginosa (EPA).
STUDY RATIONALE
ExPEC9V, which is currently in Phase 3 development for prevention of IED, is targeting the population
aged ≥60 years in which seasonal influenza vaccination is also frequently recommended in different
regions. To be able to deploy ExPEC9V as medically appropriate, data needs to be accrued that would
allow concurrent administration of ExPEC9V and other vaccination interventions (such as influenza
vaccination) that regularly target the population of interest. The current study will examine the
immunogenicity and safety of ExPEC9V co-administered with a high-dose (HD) quadrivalent seasonal
influenza vaccine (co-administration [CoAd] group) compared to administration of each vaccine separately
(Control group). The aim of the study is to provide an indication of whether these vaccines can be
administered concomitantly.
BENEFIT-RISK ASSESSMENT
Based on the available data and proposed safety measures, the overall benefit-risk assessment for this
clinical study is considered acceptable.
All participants will receive vaccination with a seasonal influenza vaccine, which may provide protection
against the influenza A subtype viruses and type B viruses contained in the vaccine during the season.
Safety measures are included in this protocol to minimize the potential risk to participants.
Only participants who meet all inclusion criteria and none of the exclusion criteria 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 and tolerability assessments will be performed at scheduled visits during the
study, as described in the Schedule of Activities (SoA).
After each vaccination, participants will closely be observed by study staff for at least 30 minutes.
Participants will use an eDiary to document solicited signs and symptoms. The investigator or
designee will document unsolicited AEs. SAEs and MAAEs will be collected until 6 months after
the last vaccination.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
8
Status: Approved, Date: 22 September 2023
All AEs, MAAEs, and SAEs will be followed by the investigator until clinical resolution or until
a clinically stable condition is reached, or until the participant has been deemed lost to follow-up.
An early exit visit will be conducted for those participants who withdraw from the study before
Day 210, but who do not withdraw consent. Participants who wish to withdraw consent from
participation in the study will be offered an early exit visit (prior to formal withdrawal of consent).
Safety issues that arise from this study will be reviewed by an Independent Data Monitoring
Committee (IDMC) on an ad hoc basis, including all related SAEs and all fatal cases.
OBJECTIVES AND ENDPOINTS
Objectives 
Endpoints
Primary
To demonstrate the non-inferiority of the humoral 
immune response to the 4 influenza vaccine strains 
after concomitant administration of ExPEC9V and a 
HD quadrivalent seasonal influenza vaccine versus the 
administration of a HD quadrivalent seasonal 
influenza vaccine administered alone. 
Antibody hemagglutination
inhibition (HI) titers as measured by
HI assay against each of the
4 influenza vaccine strains, 29 days
after the administration of a HD
quadrivalent seasonal influenza
vaccine.
To demonstrate the non-inferiority of the humoral 
immune response against the vaccine O-serotype 
antigens after concomitant administration of 
ExPEC9V and a HD quadrivalent seasonal influenza 
vaccine versus the administration of ExPEC9V 
administered alone.
Antibody titers to vaccine
O-serotype antigens, as determined
by multiplex ECL-based
immunoassay 29 days after
administration of ExPEC9V.
Secondary
To compare seroconversion rates against the 
4 influenza vaccine strains after the concomitant 
administration of ExPEC9V and a HD quadrivalent 
seasonal influenza vaccine versus the administration 
of a HD quadrivalent seasonal influenza vaccine 
alone.
Seroconversion is defined for each of
the 4 influenza vaccine strains at
29 days after the administration of a
HD quadrivalent seasonal influenza
vaccine:
HI titer ≥1:40 in participants
with a prevaccination HI titer of
<1:10, or
a ≥4-fold HI titer increase in
participants with a
prevaccination HI titer of
≥1:10.
To compare seroprotection rates against the 
4 influenza vaccine strains after the concomitant 
administration of ExPEC9V and a HD quadrivalent 
seasonal influenza vaccine versus the administration 
of a HD quadrivalent seasonal influenza vaccine 
alone.
Seroprotection is defined for each of
the 4 influenza vaccine strains as HI
titer ≥1:40 at 29 days after the
administration of a HD quadrivalent
seasonal influenza vaccine.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
9
Status: Approved, Date: 22 September 2023
Objectives 
Endpoints
To assess the safety and reactogenicity of ExPEC9V 
when administered separately or concomitantly with a 
HD quadrivalent seasonal influenza vaccine 
Solicited local (injection site) and
systemic AEs for 14 days post each
vaccination.
Unsolicited AEs for 29 days post
each vaccination.
MAAEs collected from
administration of the first
vaccination until 6 months post last
vaccination.
SAEs collected from the
administration of the first
vaccination until 6 months post last
vaccination.
To evaluate the immunogenicity of ExPEC9V when  
administered separately or concomitantly with a HD 
quadrivalent seasonal influenza vaccine. 
Antibody titers to vaccine
O-serotype antigens and EPA as
determined by multiplex ECL-based
immunoassay on Days 1, 30, and
59.
To further evaluate the immunogenicity of ExPEC9V 
when administered separately or concomitantly with a 
HD quadrivalent seasonal influenza vaccine. 
Opsonophagocytic antibody titers to
vaccine O-serotype antigens as
determined by MOPA 29 days after
administration of ExPEC9V.
To evaluate the immunogenicity of ExPEC9V 
between participants with a history of UTI to those 
without a UTI history. 
Antibody titers to vaccine
O-serotype antigens, in participants
reporting a history of UTI at
enrollment and participants without
a UTI history at enrollment, as
determined by multiplex ECL-based
immunoassay 29 days after
administration of ExPEC9V.
To further evaluate the immunogenicity of ExPEC9V 
between participants with a history of UTI to those 
without a UTI history. 
Opsonophagocytic antibody titers to
vaccine O-serotype antigens, in
participants reporting a history of
UTI at enrollment and participants
without a UTI history at enrollment,
as determined by MOPA 29 days
after administration of ExPEC9V.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
10
Status: Approved, Date: 22 September 2023
HYPOTHESES
To demonstrate the non-inferiority of the humoral immune response to the 4 influenza vaccine strains after
concomitant administration of ExPEC9V and a HD quadrivalent seasonal influenza vaccine versus the
administration of a HD quadrivalent seasonal influenza vaccine administered alone,
AND
to demonstrate the non-inferiority of the humoral immune response against the O-serotype antigens after
concomitant administration of ExPEC9V and a HD quadrivalent seasonal influenza vaccine versus the
administration of ExPEC9V administered alone,
the following hypotheses will be tested:
Null Hypothesis:
For at least 1 of the 4 influenza vaccine strains: the GMT of HI antibody titers against the considered
vaccine strain, 29 days after concomitant administration of ExPEC9V and a HD quadrivalent seasonal
influenza vaccine is inferior by at least 1.5-fold to the GMT 29 days after the administration of a HD
quadrivalent seasonal influenza vaccine alone.
OR
For at least 1 of the 9 O-serotype antigens: the GMT of antibody titers against the considered
O-serotype antigen 29 days after concomitant administration of ExPEC9V and a HD quadrivalent
seasonal influenza vaccine is inferior by at least 1.5-fold to the GMT 29 days after the administration
of ExPEC9V alone.
Alternative Hypothesis:
For each of the 4 influenza vaccine strains: the GMT of HI antibody titers 29 days after concomitant
administration of ExPEC9V and a HD quadrivalent seasonal influenza vaccine is non-inferior to the
GMT 29 days after the administration of a HD quadrivalent seasonal influenza vaccine alone, using a
non-inferiority margin of1.5, for the ratio GMTControl group/GMTCoAd group.
AND
For each of the 9 O-serotype antigens: the GMT of antibody titers 29 days after concomitant
administration of ExPEC9V and a HD quadrivalent seasonal influenza vaccine is non-inferior to the
GMT 29 days after the administration of ExPEC9V alone, using a non-inferiority margin of 1.5, for
the ratioGMTControl group/GMTCoAd group.
OVERALL DESIGN
This is a randomized, double-blind, placebo-controlled, parallel group, multicenter Phase 3 study in adult
participants aged 65 years and older. A target of approximately 932 participants will be randomized in
parallel in this study in a 1:1 ratio to 1 of 2 groups. Group 1 (CoAd group) will receive ExPEC9V on Day 1
administered at the same time as HD quadrivalent seasonal influenza vaccine, and placebo on Day 30.
Group 2 (Control group) will receive placebo on Day 1 administered at the same time as HD quadrivalent
seasonal influenza vaccine, and ExPEC9V on Day 30. All study vaccinations will be given by the IM route.
Group  
N 
Day 1 
Day 30
1 (CoAd group) 
~466 
ExPEC9V + HD quadrivalent seasonal influenza vaccine 
Placebo
2 (Control group) 
~466 
Placebo + HD quadrivalent seasonal influenza vaccine 
ExPEC9V
N = number of participants
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
11
Status: Approved, Date: 22 September 2023
After each vaccination, participants will be observed for at least 30 minutes for presence of any acute
reactions and solicited events. Any unsolicited AEs, solicited local (injection site) or systemic AEs, and
vital signs (systolic and diastolic blood pressure [sitting], heart rate, respiratory rate, and body temperature)
will be documented by study-site personnel following this observation period. In addition, participants will
record solicited signs and symptoms in an eDiary beginning on the evening of the vaccination day and on
a daily basis for 14 days post-vaccination.
Unsolicited AEs will be reported for 29 days post-vaccination. SAEs, MAAEs, and AEs leading to
discontinuation from the 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.
Blood will be collected from all participants to assess humoral immune responses on each vaccination day
(prevaccination) and at 29 days after the second study vaccination.
The end of the study is defined as the last participant’s last visit.
NUMBER OF PARTICIPANTS
Approximately 932 participants will be randomized in parallel in this study in a 1:1 ratio to 1 of 2 groups.
VACCINATION GROUPS AND DURATION
ExPEC9V (VAC52416): Escherichia coli (E. coli) bioconjugate vaccine in phosphate buffered solution
containing O-antigen PSs of ExPEC serotypes O1A, O2, O4, O6A, O15, O16, O18A, O25B, and O75
separately bioconjugated to the EPA carrier protein. Participants will receive a single 0.5 mL IM (deltoid)
injection of ExPEC9V on Day 1 (CoAd group) or Day 30 (Control group). ExPEC9V will be supplied in
2-R vials at a concentration of 176 µg PS/mL. The PS content of the dose to be tested in the present study
is 88 μg/dose.
HD Quadrivalent Seasonal Influenza Vaccine: The influenza vaccine that will be used in this study is a
suspension for IM injection supplied in a 0.7-mL single-dose prefilled syringe. Each dose of HD
quadrivalent seasonal influenza vaccine contains 240 µg of hemagglutinin (HA): 60 µg of each of
4 influenza strains (2 influenza A strains and 2 influenza B strains), matched for the 2023-2024 season in
the Northern Hemisphere.
Placebo: Sodium chloride 0.9% w/v. A single 0.5 mL IM (deltoid) injection of placebo will be administered
on Day 1 (Control group) or Day 30 (CoAd group). The placebo for this study will be supplied by the
sponsor as a commercially available injectable solution of 9 mg/mL Sodium Chloride (0.9% w/v).
On Day 1, each participant will receive 2 IM injections, 1 in each arm; on Day 30, each participant will
receive 1 IM injection. The right arm should be used for seasonal influenza vaccination on Day 1; the left
arm should be used for ExPEC9V or placebo on Days 1 and 30.
The study duration will be approximately 7 months per participant. The study comprises screening to be
performed within  8 days of Day 1, vaccination for each participant on Days 1 and 30 with a 29-day
follow-up period after each vaccination, and collection of SAEs and MAAEs until 6 months after the last
study vaccination.
IMMUNOGENICITY EVALUATIONS
Venous blood samples of approximately 30 mL will be collected for the determination of humoral immune
responses.
For assessment of immunogenicity, serum IgG antibody levels elicited by ExPEC9V against each of the
9 vaccine O-serotypes and the carrier protein EPA will be measured by a validated multiplex ECL-based
immunoassay. Additionally, functional antibodies will be evaluated by a validated MOPA.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
12
Status: Approved, Date: 22 September 2023
Antibody titers against influenza virus strains recommended by the WHO for use in 2023-2024 in the
Northern Hemisphere season will be measured using validated HI assays.
SAFETY EVALUATIONS
Safety assessments will include the monitoring of AEs, MAAEs, physical examinations, and vital signs.
Solicited AEs, collected through a participant eDiary, will be recorded for each vaccination from the time
of vaccination until 14 days post-vaccination. Unsolicited AEs and special reporting situations will be
collected for each vaccination from the time of vaccination until 29 days post-vaccination. SAEs, MAAEs,
and AEs leading to discontinuation from the study/vaccination (regardless of the causal relationship) are to
be reported from the moment of first study vaccination until completion of the participant’s last
study-related procedure, which may include contact for safety follow-up. All AEs will be followed until
resolution or until clinically stable.
AEs, MAAEs, 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.
Safety issues that arise from this study will be reviewed by an IDMC on an ad hoc basis, including all
related SAEs and all fatal cases.
STATISTICAL METHODS
Sample Size Determination
Sample size calculations are performed under the following assumptions:
No effect of co-administration of ExPEC9V and seasonal influenza vaccine on the immune response
against influenza as measured by HI antibody titers against the 4 influenza vaccine strains at 29 days
after the administration of influenza vaccine.
A standard deviation of 0.5 at the log10 scale for HI antibody titers against the 4 influenza vaccine
strains at 29 days after the administration of influenza vaccine (with or without ExPEC9V).
No effect of co-administration of ExPEC9V and seasonal influenza vaccine on the immune response
against the O-serotype antigens as measured by antibody titers against the 9 O-serotype antigens at
29 days after the administration of ExPEC9V.
A standard deviation of 0.6 at the log10 scale for ExPEC9V antibody titers at 29 days after the
administration of ExPEC9V (with or without seasonal influenza vaccine).
A non-inferiority margin of 1.5.
2-sided α of 5%.
A total of 419 evaluable participants per group are needed to have 99.91% power to show non-inferiority
in HI antibody titers for 1 influenza vaccine strain and to have 98.88% power to show non-inferiority in
antibody titers against 1 O-serotype antigen. With this sample size, the overall power to show
non-inferiority in HI antibody titers against each of the 4 influenza vaccine strains at 29 days after the
administration of seasonal influenza vaccine as well as non-inferiority in antibody titers against each of the
9 O-serotype antigens at 29 days after the administration of ExPEC9V is at least 90% (see table below).
1 comparison 
All comparisons
Flu NI (SD=0.5) 
99.91%  
99.64% (4 comparisons)
ExPEC9V NI (SD=0.6) 
98.88% 
90.36% (9 comparisons)
Total 
> 90% power
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
13
Status: Approved, Date: 22 September 2023
To account for 10% exclusions from the per protocol set (see below for definitions of analysis sets),
drop-outs and missing samples, approximately 466 participants per group should be enrolled, resulting in a
total sample size of approximately 932 participants.
Participant Analysis Sets
Vaccination assignment will follow the as-treated principle.
The Full Analysis (FA) Set will include all participants who received at least 1 study vaccination, regardless
of the occurrence of protocol deviations and vaccine type (seasonal influenza, ExPEC9V, or placebo).
All safety and participant information analyses will be based on the FA Set.
The Per-protocol Influenza Immunogenicity (PPII) Set will include all randomized participants who
received the first study vaccination (ExPEC9V in combination with seasonal influenza vaccine for the
CoAd group and seasonal influenza vaccine alone for the Control group), and for whom immunogenicity
data are available for at least one of the influenza strains in the vaccine. Samples taken after a participant
experiences a major protocol deviation expected to impact the immunogenicity outcomes will be excluded
from the PPII analysis.
The Per-protocol ExPEC9V Immunogenicity (PPEI) Set will include all randomized participants who
received ExPEC9V in combination with seasonal influenza vaccine for the CoAd group and ExPEC9V
alone for the Control group and for whom O-antigen immunogenicity data are available. Samples taken
after a participant experiences a major protocol deviation expected to impact the immunogenicity outcomes
will be excluded from the PPEI analysis.
The list of major protocol deviations that would lead to elimination from the immunogenicity analysis will
be specified in the SAP  or major protocol violation criteria document, which will be finalized before
database lock and unblinding.
The primary analysis set for analyses related to influenza immunogenicity is the PPII Set, the primary
analysis set for analyses related to O-antigen immunogenicity is the PPEI Set. As a sensitivity analysis, key
tables may also be based on the FA Set.
Immunogenicity Analyses
The primary immunogenicity objectives will be assessed by calculating:
The 2-sided 95% CIs for the difference in log10-transformed HI antibody titers against each of the
4 influenza vaccine strains at 29 days after the administration of the HD quadrivalent seasonal
influenza vaccine between the Control and the CoAd group.
The 2-sided 95% CIs for the difference in log10-transformed O-serotype antibody titers against each
of the 9 O-serotypes at 29 days after the administration of ExPEC9V between the Control and the
CoAd group.
For HI antibody titers against each of the 4 influenza vaccine strains and for O-serotype antibody titers
against each of the 9 O-serotypes, an ANOVA model will be fitted with the respective titers as dependent
variable and group (Control or CoAd), age category, and history of UTI (as stratified) as independent
variables. Based on these ANOVA models, the CIs around the difference will be calculated and will be
back-transformed (by exponentiation) to CIs around a GMT ratio (GMTControl group/GMTCoAd group) and
compared to the non-inferiority limit of 1.5.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
14
Status: Approved, Date: 22 September 2023
Only if the upper bound of the 2-sided 95% CI for the GMT ratio (Control group/CoAd group) of the
HI antibody titers for each of the 4 vaccine strains and of the O-serotype antibody titers for each of the
9 O-serotype antigens lies below 1.5, non-inferiority of co-administration versus separate administration
will be concluded for both vaccines (seasonal influenza vaccine and ExPEC9V). If 1 or more confidence
limits for the GMT ratio exceed 1.5, non-inferiority cannot be concluded.
As a sensitivity analysis to assess the impact of baseline titers, the primary endpoint will also be evaluated
adjusting for the respective baseline titers. For immunogenicity, baseline is considered as the last
assessment prevaccination. In a second sensitivity analysis, different variances between the groups will be
allowed. Therefore, the CIs will be calculated via Welch’s ANOVA.
Seroconversion is defined for each of the 4 influenza vaccine strains at 29 days after the administration of
a seasonal influenza vaccine as:
HI titer ≥1:40 in participants with a prevaccination HI titer of <1:10, or
a ≥4-fold HI titer increase in participants with a prevaccination HI titer of ≥1:10
Seroprotection is defined for each of the 4 influenza vaccine strains as HI titer ≥1:40 at 29 days after the
administration of a seasonal influenza vaccine.
The difference in proportions of seroconverted and seroprotected participants between the Control and the
CoAd group will be estimated together with the 2-sided 95% CIs (calculated using Wilson’s score method).
Additionally, HI antibody titers and O-serotype antibody titers will be summarized with descriptive
statistics.
Safety Analyses
No formal statistical testing of safety data is planned. All safety data will be analyzed descriptively by
group. All safety analyses will be based on the FA Set.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
15
Status: Approved, Date: 22 September 2023
1.2. 
Schema
Figure 1: 
Schematic Overview of the Study
* Screening and vaccination may be split into 2 visits in consultation with the sponsor or its delegate, for example
when a criterion for temporarily delaying study vaccine administration (see Section 5.5., Criteria for Temporarily
Delaying Study Vaccine Administration) is met.
** By telephone.
*** In case any of the criteria for temporarily delaying study vaccine administration (see Section 5.5., Criteria for
Temporarily Delaying Study Vaccine Administration) are met at Visit 3 (Day 30), the administration of the second
study vaccination needs to be delayed (up to a maximum of 10 days on top of the allowed time window of Visit 3
[±7 days]). The immunogenicity and safety assessments of Visit 3 should still be performed on the actual Day 30
(±7 days).
NCT06134804

NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
17
Status: Approved, Date: 22 September 2023
AE = adverse event; d = days; ICF = informed consent form; mo = months; MAAE = medically-attended adverse event; SAE = serious adverse event;
vac = vaccination
telephone contact or other means of communication; 
prevaccination; 
pre- and post-vaccination; 
solicited local (injection site) and systemic AEs will
be collected via participant eDiary from vaccination until 14 days after each vaccination; 
if within 14 days of the previous vaccination; 
if within 29 days of
the previous vaccination
Footnotes:
a. 
Visits that cannot be conducted in person at the study site may be conducted as home health visit after sponsor approval.
b. 
Safety visits and early exit visit will be by telephone.
c. 
An early exit visit will be conducted as soon as possible for those participants who are unable to continue participation in the study and withdraw from the
study before Day 210, but who do not withdraw consent. Participants who wish to withdraw consent from participation in the study will be offered an early
exit visit (prior to formal withdrawal of consent).
d. 
Screening and vaccination may be split into 2 visits in consultation with the sponsor or its delegate, for example when a criterion for temporarily delaying
study vaccine administration (see Section 5.5. Criteria for Temporarily Delaying Study Vaccine Administration) is met. Every effort should be made for
split visits to occur preferably within 3 to 5 days and no later than 10 days, and prevaccination vital signs should be repeated on the day of vaccination if
this visit is split.
e. 
Signing of the ICF should be done before any study-related activity.
f. 
Information about planned surgeries and/or procedures should be reported. Medical history of all participants will be recorded in the eCRF. Participants will
be specifically questioned regarding the medical history of UTI. This includes any uncomplicated, complicated, or recurrent UTIs that were diagnosed by a
physician (or qualified healthcare provider) and that required antimicrobial therapy. The details will be collected in the eCRF. Note: a history of isolated
male accessory gland infections will not be considered as a history of UTI.
g. 
Prestudy therapies administered up to 30 days before the first study vaccination must be recorded on Day 1.
h. 
Sitting systolic and diastolic blood pressure, heart rate, and respiratory rate after at least 5 minutes rest on Days 1 and 30. At non-vaccination visits, vital
signs will be measured if deemed necessary by the investigator.
i. 
General physical examination; it is at the investigator’s discretion how detailed the examination (which body systems are to be covered) is deemed needed.
At any other visit, a targeted (abbreviated and symptom-directed) examination may be performed if deemed necessary by the investigator based on any
clinically relevant issues, clinically relevant symptoms, and medical history.
j. 
Inclusion Criterion 2 and Exclusion Criteria 2, 4, 5, 6, 9, 10, 11 and 12.
k. 
Investigator must check for clinically significant acute illness at the time of vaccination, body temperature ≥38.0°C (≥100.4°F) within 24 hours prior to the
planned time of vaccination, an illness which in the judgment of the investigator may interfere with reactogenicity or safety assessments, and whether the
participant recently received a medically indicated vaccination. If any of these events occur at the scheduled time for the first vaccination, randomization at
a later date within the screening period (allowed window up to 8 days) is permitted. If any of these events occur at the scheduled time for the second
vaccination, the vaccination can be delayed up to 10 days on top of the allowed time window of Visit 3 (±7 days). The immunogenicity and safety
assessments of Visit 3 should still be performed on the actual Day 30 (±7 days).
l. 
After each vaccination, participants will be observed for at least 30 minutes for presence of any acute reactions and solicited events. Any unsolicited AEs,
solicited local (injection site) or systemic AEs, and vital signs (systolic and diastolic blood pressure [sitting], heart rate, respiratory rate, and body
temperature) will be documented by study-site personnel following this observation period.
m. Includes the assessment of the severity of solicited AEs during the Visit 2 and Visit 4 phone calls.
n. 
Includes the assessment of the severity of unsolicited AEs and the occurrence of special reporting situations during all visits up to 29 days post-vaccination,
including the Visit 2 and Visit 4 phone calls.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
18
Status: Approved, Date: 22 September 2023
o. 
Concomitant therapies will be collected from the time of first study vaccination through 29 days after the last study vaccination when associated with an
AE, and from ICF signature until 6 months after the last study vaccination when associated with an SAE. Concomitant therapies associated with solicited
AEs will be collected by the participants in the participant eDiary from the time of study vaccination through 14 days after each vaccination.
p. 
Rulers and thermometers will be distributed at Visit 1 and at Visit 3, if applicable.
q. 
eDiary entries will be reviewed with the participant by a qualified and delegated study staff member (eg, investigator, sub-investigator, or study nurse). The
delegated study staff member grades any signs or symptoms using the toxicity grading scale (Appendix 5: Toxicity Grading Scale) and will complete their
assessment in the relevant sections of the eCRF. The eDiary review and grading of symptoms are done under the oversight of the investigator or a delegated
physician.
r. 
Aliquots of serum samples collected for immunogenicity tests can be reconverted for participant’s safety purposes upon sponsor request.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
19
Status: Approved, Date: 22 September 2023
2. 
INTRODUCTION
ExPEC9V (primary compound number: VAC52416) is a 9-valent vaccine candidate in
development for active immunization for the prevention of invasive extraintestinal pathogenic
Escherichia coli (ExPEC) disease (IED) in adults 60 years of age and older. ExPEC9V consists of
the O-antigen polysaccharides (PSs) of the ExPEC serotypes O1A, O2, O4, O6A, O15, O16, O18A,
O25B, and O75 separately bioconjugated to the carrier protein, a genetically detoxified form of
exotoxin A derived from Pseudomonas aeruginosa (EPA).
For the most comprehensive nonclinical and clinical information regarding VAC52416
(JNJ-78901563), refer to the latest version of the IB for VAC52416 (JNJ-78901563).
The term “study vaccination” throughout the protocol, refers to ExPEC9V, placebo, or the
high-dose (HD) quadrivalent seasonal influenza vaccine as defined in Section 6.1., Study
Vaccinations Administered.
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 non-inferiority criteria used in this study are based on guidance from regulatory authorities
(for details, refer to Section 9.2., Sample Size Determination).
2.1. 
Study Rationale
ExPEC is a leading and increasing cause of bacteremia/bloodstream infections worldwide and
comprises 17% to 37% of blood isolates (De Kraker 2013, Johnson 2003, Laupland 2014). In the
US, the overall annual incidence of ExPEC bloodstream infections in adults ranges between
30 and 50/100,000 person-years (Laupland 2014, Williamson 2013). In Europe, the number of
cases of ExPEC bacteremia annually increased by 8.1% between 2002 and 2008 (De Kraker 2013).
IED is defined as an acute illness consistent with systemic bacterial infection, which is
microbiologically confirmed either by the isolation and identification of E. coli from blood or any
other sterile body sites, or by the isolation and identification of E. coli from urine in a patient with
urosepsis and no other identifiable source of infection. Although IED affects all ages, adults aged
≥60 years have an increased risk of developing IED, including bacteremia and sepsis. In a
retrospective population-based study in the US from 1998 to 2007, the incidence of E. coli
bloodstream infections was shown to increase markedly with age from 60 years onwards. The
incidence rates in  adults aged ≥60 years were estimated to be between 136 to 152/100,000
person-years; while by age stratum, incidence rates were estimated at 100/100,000 person-years
in adults aged 60 to 79 years, and 300/100,000 person-years in adults aged ≥80 years. The urinary
tract was found to be the most common primary source of infection (79.8%) (Al-Hasan 2009a,
2009b).
ExPEC9V, which  is currently in Phase 3 development for prevention of IED, is targeting the
population aged ≥60 years in which seasonal influenza vaccination is also frequently
recommended in different regions. To be able to deploy ExPEC9V as medically appropriate, data
needs to be accrued that would allow concurrent administration of ExPEC9V and other vaccination
interventions (such as influenza vaccination) that regularly target the population of interest. The
current study will examine the immunogenicity and safety of ExPEC9V co-administered with a
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
20
Status: Approved, Date: 22 September 2023
HD  quadrivalent seasonal influenza vaccine (co-administration [CoAd] group) compared to
administration of each vaccine separately (Control group). The aim is to provide an indication of
whether these vaccines can be administered concomitantly.
The present study also aims to include participants (aged ≥65 years) with and without a previous
history of UTI to allow a comparison of vaccine-elicited immunogenicity between the
2 populations (ie, with a previous UTI history versus without a previous UTI history). Participants
with a previous UTI history, particularly if some of the UTIs were attributable to E.coli infection,
have been observed to elaborate higher baseline immune responses targeting E.coli O-antigens, as
shown in the VAC52416BAC1001 study Cohort 2 (see Section 2.2., Background). This
observation needs to be further investigated through a comparison of immunogenicity elicited by
the vaccine for the 2 aforementioned populations.
2.2. 
Background
Nonclinical Studies
In a nonclinical immunogenicity study in NZW rabbits (TV-TEC-179827), 3 IM injections with
ExPEC9V, 10-valent extraintestinal pathogenic Escherichia coli vaccine (ExPEC10V), or saline
control were administered 2 weeks apart. ExPEC9V and ExPEC10V were shown to be
immunogenic in this study.
A 4-week intermittent repeat-dose toxicity and local tolerance study (TOX13465, GLP  study),
with ExPEC10V was conducted in NZW rabbits. ExPEC10V was administered via IM injection
once every 2 weeks, with a total of 3 IM injections. ExPEC10V was well tolerated in this study.
All vaccine-related effects noted were consistent with a normal immunologic response to the
vaccine and were not considered to be adverse.
For further details on the nonclinical immunogenicity and toxicology studies with ExPEC9V
and/or ExPEC10V, refer to the latest version of the ExPEC9V IB.
Clinical Studies
ExPEC9V is a vaccine candidate for active immunization for the prevention of invasive
Escherichia coli disease (IED), in adults 60 years of age and older. ExPEC9V is being developed
based on the sponsor’s preceding clinical experience with ExPEC10V and ExPEC4V, an earlier
vaccine candidate which comprised 4 O-antigen conjugates (O1A, O2, O6A, and O25B).
The ExPEC4V vaccine has been evaluated in 2 completed Phase 1 clinical studies (GVXN EC-4V
and 63871860BAC1001), and 2 completed Phase 2 clinical studies (63871860BAC2001 and
63871860BAC2003). ExPEC4V was well tolerated in these studies and no vaccine-related safety
signals were observed at doses up to 16 µg PS per serotype. In each study, the ExPEC4V vaccine
was shown to be immunogenic against all vaccine serotypes, demonstrating a dose-dependent
vaccine immune response and O-antigen specific IgG titer increases, as measured by an ELISA.
Functional activity of the antibodies was demonstrated with an ExPEC4V-optimized OPA.
Immunogenicity analysis from study 63871860BAC2001 has demonstrated durability of the
immune response through 3 years after vaccination with ExPEC4V  (Synoptic Clinical Study
Report 63871860BAC2001).
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
21
Status: Approved, Date: 22 September 2023
ExPEC10V is currently being investigated in the ongoing study VAC52416BAC1001.
VAC52416BAC1001 is a randomized, multicenter, first-in-human Phase 1/2a study to evaluate
the safety, reactogenicity, and immunogenicity of 3 different doses of ExPEC10V (serotypes O1A,
O2, O4, O6A, O8, O15, O16, O18A, O25B, and O75) and to select an optimal dose of ExPEC10V
for further clinical development. This study includes 2 cohorts. In Cohort 1, 416 participants aged
≥60 to ≤85 years in stable health received study vaccination (ExPEC10V [low, medium, or high
dose], ExPEC4V, or Prevnar 13®). The 3 dose levels of ExPEC10V were evaluated in
approximately 100 participants per dose level. Cohort 1 also included reference groups who
received ExPEC4V or Prevnar 13® (approximately 52 participants per group). Results from
Cohort 1 indicated that total IgG titers increased significantly for all ExPEC10V doses. A 2-fold
or greater increase in IgG titers, for all serotypes except O8 and O75, was observed for at least
82% of participants who received the high dose. MOPA results were generally consistent with
ECL data: increased functional antibody titers were observed on Day 15 for all ExPEC10V
serotypes and dose groups, with the exception of serotype O8. The MOPA data for serotype O8
were further investigated and a functional antibody response for this serotype could not be
demonstrated in the qualified MOPA assay used. This prompted the sponsor to investigate a new
formulation (ExPEC9V), excluding the O8 serotype, in study VAC52416BAC3001, discussed
below.
Safety results from study VAC52416BAC1001 (including preliminary results for Cohort 2)
showed that the most frequent local solicited AE was pain/tenderness and the most frequently
reported systemic AEs were myalgia, headache, and fatigue. While several of the observed
solicited AEs occurred early, a trend towards late onset of local solicited AEs was observed in the
VAC52416BAC1001 participants. Injection site erythema and swelling were the most common
late onset events (time to first onset >5 days after vaccination) in participants from the combined
ExPEC10V groups in both Cohorts 1 and 2. A trend towards increased local reactogenicity with
higher doses of ExPEC10V was observed in Cohort 1. The most frequent unsolicited AE assessed
as related to the vaccine was injection site pruritus, reported by <3% of the participants from the
combined ExPEC10V groups in both Cohorts 1 and 2.
The ongoing Phase 3 study VAC52416BAC3001 was the first study in which ExPEC9V was
administered to humans. The study is a randomized, double-blind, placebo-controlled,
parallel-group, multicenter, interventional Phase 3 study  to investigate the efficacy, safety,
reactogenicity, and immunogenicity of ExPEC9V in approximately 18,556 medically stable adults
aged ≥60 years with a history of UTI in the past 2 years. Removal of the O8 serotype is expected
to result in a change of ExPEC9V O-serotype coverage from approximately 70% (ExPEC10V) to
approximately 65% of ExPEC associated bloodstream infections in adults aged ≥60 years. In
May 2022, an IDMC meeting was held to review safety information from the first 500 randomized
participants who had completed the Day 30 visit (or discontinued earlier). Following this safety
review, the IDMC recommended that the study could continue unmodified until the next scheduled
meeting.
The present Phase 3 study VAC52416BAC3002 will investigate the immunogenicity, safety, and
reactogenicity of the selected dose of ExPEC9V and HD quadrivalent seasonal influenza vaccine,
with and without co-administration, in medically stable adults aged ≥65 years.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
22
Status: Approved, Date: 22 September 2023
2.2.1. 
Seasonal Influenza Vaccine
The HD quadrivalent seasonal influenza vaccine that will be used in this study is indicated for
active immunization for prevention of disease caused by influenza A subtype viruses and type B
viruses contained in the vaccine in adults aged 65 years and older. The influenza strains contained
in the vaccine are matched for the 2023-2024 Northern Hemisphere season. HD quadrivalent
seasonal influenza vaccine is widely used in the United Kingdom and US.
For further information regarding HD quadrivalent seasonal influenza vaccine refer to the
applicable product information sheet.
2.3. 
Benefit-risk Assessment
2.3.1. 
Risks Related to Study Participation
The following potential risks for ExPEC9V will be monitored during the study and are specified
in the protocol:
Risks Related to ExPEC9V
Based on 2 completed Phase 1 studies and 2 completed Phase 2 studies in the ExPEC4V
development program, most solicited (local and systemic) AEs started on Days 1 to 3
post-vaccination. Headache and fatigue/tiredness were the most frequent solicited AEs, reported
as early onset events, with a median time of onset of 2 and 3 days, respectively. Late onset solicited
(mainly local) AEs were observed starting Days 6 to 8 post-vaccination. Pain/tenderness
represented a majority of the late onset AEs and were Grade 1 in severity. There was a tendency
for higher incidence of late onset AEs with higher ExPEC4V doses.
Late onset solicited AEs were also observed in ExPEC10V development program. The median
time to first onset of local solicited AEs was 2 to 2.5 days after vaccination for those in the
ExPEC10V dose groups. The most frequent solicited AEs, pain/tenderness, fatigue, myalgia, and
headache occurred mostly as early onset events. Injection site erythema and swelling occurred as
late onset events (time to first onset >5 days after vaccination) in the majority of participants from
the combined ExPEC10V groups. In the combined ExPEC10V groups, 8 (2.6%) participants
experienced late onset AEs with Grade 3 severity. A trend towards increased local reactogenicity
with higher doses of ExPEC10V was observed.
Risks Related to HD QuadrivalentSeasonal Influenza Vaccine
HD quadrivalent seasonal influenza vaccine is indicated to be used for individuals aged 65 years
or above in the countries participating to this study. HD quadrivalent seasonal influenza vaccine
will be administered in the study following the approved prescribing information(s).
In adults, the most common (≥10%) solicited local adverse reaction after HD quadrivalent seasonal
influenza vaccine administration was pain (41.3% to 42.6%), the most common solicited systemic
adverse reactions were myalgia (22.7%  to 23.8%), headache (14.4%  to 17.3%), and malaise
(13.2% to 15.6%). Overall, adverse reactions were generally less frequent in participants 65 years
of age and older than in participants 60 to 64 years of age.
For further details, refer to the HD quadrivalent seasonal influenza vaccine package insert.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
23
Status: Approved, Date: 22 September 2023
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 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.
Polyneuropathy events (eg, Guillain-Barré Syndrome) have been reported with some vaccines.
Pregnancy and Birth Control
The effect of ExPEC9V on a fetus or nursing baby is unknown. Participants may therefore only
participate if they are postmenopausal (defined as no menses for 12 months without an alternative
medical cause) and not intending to conceive by any methods. Participants who are surgically
sterile are also eligible for the study. Follow-up information regarding the outcome of the
pregnancy and any postnatal sequelae in the infant will be required.
Because the effect on sperm is unknown, participants must inform the study-site personnel if their
partner becomes pregnant during the study. Follow-up information regarding the outcome of the
pregnancy and any postnatal sequelae in the infant will be required upon the consent provided by
the partner.
Risks Related to Concomitant Vaccination
Concomitant vaccination might have an influence on both the safety profile and immunogenicity
of ExPEC9V. Likewise, ExPEC9V might have an influence on both the safety profile and
immunogenicity of any concomitant vaccination.
In order to avoid misinterpretation of adverse reactions and potential immune interference,
vaccination with licensed live attenuated vaccines is prohibited within 28 days before or after the
administration of the study vaccination. Vaccination with other licensed vaccines (not live)
(eg, COVID-19, tetanus, hepatitis A, hepatitis B, rabies) is prohibited within 14 days before or
after the administration of the study vaccine. If a vaccine is indicated in a post-exposure setting
(eg, rabies or tetanus), it must take priority over the study vaccine.
Vaccination with a vaccine authorized for emergency use (eg, EUA, CMA, or a similar program)
is permitted when given at least 28 days before or after administration of the study vaccine.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
24
Status: Approved, Date: 22 September 2023
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 nonreplicating 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 draws may cause pain, tenderness, bruising, bleeding, dizziness, vaso-vagal response,
syncope, and, rarely, infection at the site where the blood is taken.
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 of Study Participation
Participants may benefit from clinical testing and physical examination.
The clinical benefits of ExPEC9V have yet to be established.
Currently, there are no effective vaccines for the prevention of IED 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.
Vaccination with a seasonal influenza vaccine may provide protection against the influenza A
subtype viruses and type B viruses contained in the vaccine during the season.
2.3.3. 
Benefit-risk Assessment of Study Participation
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 and tolerability assessments will be performed at scheduled visits
during the study, as described in the Schedule of Activities (SoA).
After each vaccination, participants will closely be observed by study staff for at least
30 minutes. Necessary emergency equipment and medications must be available in the
clinic to treat severe allergic reactions. Participants will use an electronic diary (eDiary)
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.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
25
Status: Approved, Date: 22 September 2023
The investigator or the designee will document unsolicited AEs, as indicated in
Section 8.2., Safety Assessments, Section 8.3, Adverse Events, Serious Adverse Events,
and Other Safety Reporting, and Appendix 3: Adverse Events, Serious Adverse Events,
Medically-attended Adverse Events, Product Quality Complaints, and Other Safety
Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up, and
Reporting.
After the last vaccination, participants will enter a 6-month safety follow-up period for
collection of SAEs and MAAEs.
All AEs, MAAEs, and SAEs will be followed by the investigator until clinical resolution
or until a clinically stable condition is reached, or until the participant has been deemed
lost to follow-up after demonstration of due diligence of follow-up efforts. An early exit
visit will be conducted for those participants who are unable to continue participation in
the study and withdraw from the study before Day 210, but who do not withdraw consent.
Participants who wish to withdraw consent from participation in the study will be offered
an early exit visit (prior to formal withdrawal of consent) (Section 7.2., Participant
Discontinuation/Withdrawal From the Study).
Safety issues that arise from this study will be reviewed by an IDMC on an ad hoc basis,
including all related SAEs and all fatal cases.
Several safety measures are included in this protocol to minimize the potential risk to
participants, including the following:
Study vaccinations will be discontinued in participants for the reasons included in
Section 7., Discontinuation of Study Vaccination and Participant Discontinuation/
Withdrawal From the Study.
Contraindications to vaccination are included in Section 5.5., Criteria for Temporarily
Delaying Study Vaccine Administration.
More detailed information about the known and expected benefits and risks of VAC52416
(JNJ-78901563) may be found in the Investigator's Brochure.
3. 
OBJECTIVES AND ENDPOINTS
Objectives 
Endpoints
Primary
To demonstrate the non-inferiority of the humoral 
immune response to the 4 influenza vaccine strains 
after concomitant administration of ExPEC9V and a 
HD quadrivalent seasonal influenza vaccine versus the 
administration of a HD quadrivalent seasonal 
influenza vaccine administered alone. 
Antibody hemagglutination
inhibition (HI) titers as measured by
HI assay against each of the
4 influenza vaccine strains, 29 days
after the administration of a HD
quadrivalent seasonal influenza
vaccine.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
26
Status: Approved, Date: 22 September 2023
Objectives 
Endpoints
To demonstrate the non-inferiority of the humoral 
immune response against the vaccine O-serotype 
antigens after concomitant administration of 
ExPEC9V and a HD quadrivalent seasonal influenza 
vaccine versus the administration of ExPEC9V 
administered alone.
Antibody titers to vaccine
O-serotype antigens, as determined
by multiplex ECL-based
immunoassay 29 days after
administration of ExPEC9V.
Secondary
To compare seroconversion rates against the 
4 influenza vaccine strains after the concomitant 
administration of ExPEC9V and a HD quadrivalent 
seasonal influenza vaccine versus the administration 
of a HD quadrivalent seasonal influenza vaccine 
alone.
Seroconversion is defined for each
of the 4 influenza vaccine strains at
29 days after the administration of a
HD quadrivalent seasonal influenza
vaccine:
HI titer ≥1:40 in participants
with a prevaccination HI titer
of <1:10, or
a ≥4-fold HI titer increase in
participants with a
prevaccination HI titer of
≥1:10.
To compare seroprotection rates against the 
4 influenza vaccine strains after the concomitant 
administration of ExPEC9V and a HD quadrivalent 
seasonal influenza vaccine versus the administration 
of a HD quadrivalent seasonal influenza vaccine 
alone.
Seroprotection is defined for each of
the 4 influenza vaccine strains as HI
titer ≥1:40 at 29 days after the
administration of a HD quadrivalent
seasonal influenza vaccine.
To assess the safety and reactogenicity of ExPEC9V 
when administered separately or concomitantly with a 
HD quadrivalent seasonal influenza vaccine 
Solicited local (injection site) and
systemic AEs for 14 days post each
vaccination.
Unsolicited AEs for 29 days post
each vaccination.
MAAEs collected from
administration of the first
vaccination until 6 months post last
vaccination.
SAEs collected from the
administration of the first
vaccination until 6 months post last
vaccination.
To evaluate the immunogenicity of ExPEC9V when 
administered separately or concomitantly with a HD 
quadrivalent seasonal influenza vaccine. 
Antibody titers to vaccine
O-serotype antigens and EPA as
determined by multiplex ECL-based
immunoassay on Days 1, 30, and
59.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
27
Status: Approved, Date: 22 September 2023
Objectives 
Endpoints
To further evaluate the immunogenicity of ExPEC9V 
when administered separately or concomitantly with a 
HD quadrivalent seasonal influenza vaccine. 
Opsonophagocytic antibody titers to
vaccine O-serotype antigens as
determined by MOPA 29 days after
administration of ExPEC9V.
To evaluate the immunogenicity of ExPEC9V 
between participants with a history of UTI to those 
without a UTI history. 
Antibody titers to vaccine
O-serotype antigens, in participants
reporting a history of UTI at
enrollment and participants without
a UTI history at enrollment, as
determined by multiplex ECL-based
immunoassay 29 days after
administration of ExPEC9V.
To further evaluate the immunogenicity of ExPEC9V 
between participants with a history of UTI to those 
without a UTI history. 
Opsonophagocytic antibody titers to
vaccine O-serotype antigens, in
participants reporting a history of
UTI at enrollment and participants
without a UTI history at enrollment,
as determined by MOPA 29 days
after administration of ExPEC9V.
HYPOTHESES
To demonstrate the non-inferiority of the humoral immune response to the 4 influenza vaccine
strains after concomitant administration of ExPEC9V and a HD quadrivalent seasonal influenza
vaccine versus the administration of a HD quadrivalent seasonal influenza vaccine administered
alone,
AND
to demonstrate the non-inferiority of the humoral immune response against the O-serotype
antigens after concomitant administration of ExPEC9V and a HD quadrivalent seasonal influenza
vaccine versus the administration of ExPEC9V administered alone,
the following hypotheses will be tested:
Null Hypothesis:
For at least 1 of the 4 influenza vaccine strains: the GMT of HI antibody titers against the
considered vaccine strain, 29 days after concomitant administration of ExPEC9V and a HD
quadrivalent seasonal influenza vaccine is inferior by at least 1.5-fold to the GMT 29 days
after the administration of a HD quadrivalent seasonal influenza vaccine alone.
OR
For at least 1 of the 9 O-serotype antigens: the GMT of antibody titers against the considered
O-serotype antigen 29 days after concomitant administration of ExPEC9V  and a HD
quadrivalent seasonal influenza vaccine is inferior by at least 1.5-fold to the GMT 29 days
after the administration of ExPEC9V alone.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
28
Status: Approved, Date: 22 September 2023
Alternative Hypothesis:
For each of the 4 influenza vaccine strains: the GMT of HI antibody titers 29 days after
concomitant administration of ExPEC9V and a HD quadrivalent seasonal influenza vaccine
is non-inferior to the GMT 29 days after the administration of a HD quadrivalent seasonal
influenza vaccine alone, using a non-inferiority margin of 1.5, for the ratio
GMTControl group/GMTCoAd group.
AND
For each of the 9 O-serotype antigens: the GMT of antibody titers 29 days after concomitant
administration of ExPEC9V and a HD quadrivalent seasonal influenza vaccine is non-inferior
to the GMT 29 days after the administration of ExPEC9V  alone, using a non-inferiority
margin of 1.5, for the ratio GMTControl group/GMTCoAd group.
4. 
STUDY DESIGN
4.1. 
Overall Design
This is a randomized, double-blind, placebo-controlled, parallel group, multicenter, Phase 3 study
in adult participants aged 65 years and older.
A target ofapproximately 932 participants will be randomized in parallel in this study in a 1:1 ratio
to 1 of 2 vaccination groups (Table 1). The randomization will be stratified by age category (≥65 to
<75 years, ≥75 years) and history of UTI (yes/no).
Group 1 (CoAd group) will receive ExPEC9V on Day 1 administered at the same time as HD
quadrivalent seasonal influenza vaccine, and placebo on Day 30. Group 2 (Control group) will
receive placebo on Day 1 administered at the same time as HD quadrivalent seasonal influenza
vaccine, and ExPEC9V on Day 30. All study vaccinations will be given by the IM route.
Table 1: 
Overview of the Groups, Targeted Number of Participants, and Vaccinations
Group  
N 
Day 1 
Day 30
1 (CoAd group) 
~466 
ExPEC9V + HD quadrivalent seasonal influenza vaccine 
Placebo
2 (Control group) 
~466 
Placebo + HD quadrivalent seasonal influenza vaccine 
ExPEC9V
N = number of participants.
After each vaccination, participants will be observed for at least 30 minutes for presence of any
acute reactions and solicited events. Any unsolicited AEs, solicited local (injection site) or
systemic AEs, and vital signs (systolic and diastolic blood pressure [sitting], heart rate, respiratory
rate, and body temperature)will be documented by study-site personnel following this observation
period. In addition, participants will record solicited signs and symptoms in an eDiary for 14 days
post-vaccination.
Unsolicited AEs will be reported for 29 days post-vaccination. SAEs, MAAEs, and AEs leading
to discontinuation from the 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. More details are provided in Section 8.3.1., Time Period and Frequency
for Collecting Adverse Event and Serious Adverse Event Information.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
29
Status: Approved, Date: 22 September 2023
The study duration will be approximately 7 months per participant. The study comprises screening
to be performed within 8 days ofDay 1, vaccination for each participant on Days 1 and 30 with a
29-day follow-up period after each vaccination, and collection of SAEs and MAAEs until
6 months after the last study vaccination.
Unscheduled study visits may be performed based on investigator’s clinical judgment and may
include further evaluations, as needed.
Blood will be collected from all participants to assess humoral immune responses on each
vaccination day (prevaccination) and at 29 days after the second study vaccination. Over the entire
study, the total blood volume to be collected from each participant will be approximately 90 mL.
A diagram of the study design is provided in Section 1.2, Schema (Figure 1).
An IDMC will be commissioned for this study. Refer to Committees Structure in Section 10.2,
Appendix 2: Regulatory, Ethical, and Study Oversight Considerations for details.
4.2. 
Scientific Rationale for Study Design
Blinding, Control, Study Phase/Periods, Vaccination Groups
The study will examine the immunogenicity and safety of ExPEC9V co-administered with a HD
quadrivalent seasonal influenza vaccine compared to administration of each vaccine separately. A
placebo control will be used for ExPEC9V to establish the frequency and magnitude of changes in
clinical endpoints that may occur in the absence of active vaccination. Randomization will be used
to minimize bias in the assignment of participants to vaccination groups, to increase the likelihood
that known and unknown participant attributes (eg, demographic and baseline characteristics) are
evenly balanced across vaccination groups, and to enhance the validity of statistical comparisons
across vaccination groups. Blinded vaccination will be used to reduce potential bias during data
collection and evaluation of clinical endpoints.
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.
Written consent/assent may be obtained through various sources (eg, paper or electronic such as
eConsent, eSignature, or digital signature) as determined by regulations as well as study and/or
participant preferences.
The primary ethical concern is that this study will be performed in adult participants who may
receive no benefit from participation in the study, except for compensation for the time and
inconveniences that may arise from participation in the study.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
30
Status: Approved, Date: 22 September 2023
Vaccination with a seasonal influenza vaccine may provide protection against the influenza A
subtype viruses and type B viruses contained in the vaccine. Note, interference of ExPEC9V on
the immunogenicity of seasonal influenza vaccine cannot be ruled out.
See Section 2.3., for Benefit-Risk Assessment.
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 standard of the US
Department of Health and Human Services (HHS) Office for Human Research Protections (OHRP),
and US FDA guidelines of 550 mL in any 8-week period (OHRP 1998; FDA 1998).
4.3. 
Justification for Dose
The dose of ExPEC9V to be administered in the present study is based on the primary analysis of
Cohort 1 of the ongoing ExPEC10V Phase 1/2a study (VAC52416BAC1001) (see Section 2.2.,
Background).
The dose of HD quadrivalent seasonal influenza vaccine is based on its licensed posology for the
population aged 65 years and older in the countries participating in the study, as described in the
package insert.
4.4. 
End of Study Definition
End of Study Definition
The end of study is considered as the last visit (Day 210) 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 the
Day 210 visit.
Participants who prematurely discontinue study vaccination for any reason before completion of
the Day 210 visit will not be considered to have completed the study.
5. 
STUDY POPULATION
Screening for eligible participants will be performed within 8 days before administration of the
study vaccination. Refer to Section 5.4., Screen Failures for conditions under which the repeat of
any screening procedures is 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.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
31
Status: Approved, Date: 22 September 2023
5.1. 
Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
Age
1. 
≥65 years of age, inclusive, on the day of signing the ICF.
Type of Participant and Disease Characteristics
2. 
must be medically stable at the time of vaccination such that, according to the judgment
of the investigator, hospitalization within the study period is not anticipated and the
participant appears likely to be able to remain on study through the end of
protocol-specified follow-up. A stable medical condition is defined as disease not
requiring significant change in therapy during the 6 weeks before enrollment and when
hospitalization for worsening of the disease is not anticipated. Participants will be
included on the basis of physical examination, medical history, and vital signs
performed between ICF signature and vaccination.
Weight
Not applicable.
Sex and Contraceptive/Barrier Requirements
3. 
male or female.
4. 
before randomization, a participant must be:
a. postmenopausal (postmenopausal state is defined as no menses for 12 months
without an alternative medical cause); and
b. not intending to conceive by any methods.
Note: Surgically sterile participants are also eligible for the study.
Informed Consent
5. 
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.
6. 
willing and able to adhere to the lifestyle restrictions specified in this protocol.
Additional Inclusion Criteria
7. 
agrees to not donate blood from the time of vaccination until 3 months after receiving
the last dose of study vaccine.
8. 
must be willing to provide verifiable identification, has means to be contacted and to
contact the investigator during the study.
9. 
must be able to read, understand, and complete the eDiary.
10. 
must be able to work with smartphones/tablets/computers.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
32
Status: Approved, Date: 22 September 2023
5.2. 
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from
participating in the study:
Medical Conditions
1. 
history of an underlying clinically significant acute or uncontrolled chronic medical
condition or significant cognitive impairment 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.
2. 
abnormal function of the immune system resulting from:
a. clinical conditions or their treatments expected to have an impact on the immune
response elicited by the study vaccine. Participants with clinical conditions that are
stable under treatment without the use of prohibited therapies may be enrolled at
the discretion of the investigator.
b. chronic or recurrent use of systemic corticosteroids within 3 months before
administration of study vaccine and during the study. A substantially
immunosuppressive steroid dose is considered to be ≥2 weeks of daily receipt of
20 mg of prednisone or equivalent.
Note: Ocular, topical or inhaled steroids are allowed.
c. administration of antineoplastic and immunomodulating agents (eg, cancer
chemotherapeutic 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.
3. 
history of malignancy within 5 years before screening not in the following categories:
a. participants with squamous and basal cell carcinomas of the skin and carcinoma in
situ of the cervix may be enrolled at the discretion of the investigator.
b. participants with a history of malignancy within 5 years before screening, with
minimal risk of recurrence per investigator’s judgment, can be enrolled.
c. participants with a diagnosis of localized prostate cancer may be enrolled at the
discretion of the investigator if they completed treatment (continuation of androgen
deprivation therapy is allowed) or if they remain under observation or active
surveillance. Participants who underwent radical prostatectomy or radiotherapy
maybe enrolled at the discretion of the investigator if treatment has been completed
6 months prior to the planned administration of the study vaccine.
4. 
known or suspected allergy or history of severe allergic reaction, anaphylaxis, or other
serious adverse reactions to vaccines or vaccine excipients (specifically the excipients
of the study vaccine) (refer to Investigator's Brochure).
5. 
history of severe allergic reactions (eg, anaphylaxis) to any component of the HD
quadrivalent seasonal influenza vaccine, including egg protein, or following a previous
dose of any influenza vaccine.
6. 
has had major surgery (per the investigator’s judgment) within 4 weeks before
administration of the first study vaccine or will not have recovered from surgery per
the investigator’s judgment at time of vaccination.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
33
Status: Approved, Date: 22 September 2023
7. 
history of acute polyneuropathy (eg, Guillain-Barré syndrome) or chronic
inflammatory demyelinating polyneuropathy.
8. 
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.
9. 
contraindication to IM injections and blood draws (eg, bleeding disorders).
Prior/Concomitant Therapy
10. 
received hematopoietic stem cell transplant based on medical history, treatment with
immunoglobulins in the 2 months, apheresis therapies in the 4 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.
11. 
received or plans to receive:
a. licensed live attenuated vaccines - within 28 days before or after planned
administration of the first or subsequent study vaccinations.
b. other licensed (not live) vaccines - within 14 days before or after planned
administration of the first or subsequent study vaccinations.
c. vaccination with a vaccine authorized for emergency use (eg, EUA, CMA, or a
similar program) is permitted when given at least 28 days before or after planned
administration of the first or subsequent study vaccinations.
12. 
received vaccination with seasonal influenza vaccine for the current influenza season
in the Northern Hemisphere.
13. 
received any E. coli1 or ExPEC vaccine.
Prior/Concurrent Clinical Study Experience
14. 
received an investigational drug or used an invasive investigational medical device
within 90 days, or received an investigational vaccine within 90 days before the
planned administration of the first dose of study vaccine, or is currently enrolled or
plans to participate in another investigational study during the course of this study and
before 6 months after administration of the study vaccine.
1 
E. coli vaccines include, and are not limited to, immunoactive agents used for rUTI prophylaxis and containing
E. coli immunogens, eg, inactivated whole bacterial lysates of E. coli (eg, Uromune®) or lyophilized preparation
of E. coli membrane proteins (eg, Uro-vaxom®).
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
34
Status: Approved, Date: 22 September 2023
Diagnostic Assessments
15. 
has uncontrolled HIV type 1 or type 2 infection.
Note: a participant with a stable/well-controlled HIV infection is allowed.
See Appendix 6: Specific Criteria for the Inclusion of Potential Participants with
Chronic Stable HIV, HCV, or HBV Infection.
16. 
has a diagnosis of chronic active hepatitis B or hepatitis C infection that is not medically
stable, based on judgment of the investigator.
Note: a participant with a stable and virologically suppressed hepatitis B or hepatitis
C infection is allowed.
See Appendix 6: Specific Criteria for the Inclusion of Potential Participants with
Chronic Stable HIV, HCV, or HBV Infection.
Other Exclusions
17. 
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 or CRO.
18. 
cannot communicate reliably with the investigator.
19. 
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.
20. 
who 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.
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 study vaccination is given
such that the participant no longer meets all eligibility criteria, then the participant must be
excluded from participation in the study. Section 5.4., Screen Failures, describes options for
retesting. The required documentation to support meeting the enrollment criteria is described in
Appendix 2: 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 study to be eligible for participation:
1. refer to Section 6.8., Concomitant Therapy 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.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
35
Status: Approved, Date: 22 September 2023
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. This study will use interactive web response
system (IWRS). The investigator will generate screening and enrollment logs directly from IWRS.
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
identification and age at initial informed consent. In cases where the participant is not randomized
into the study, the date seen and age at initial informed consent will be used.
Rescreening
Individuals who do not meet the criteria for participation in this study (screen failure) may be
rescreened. Rescreening is allowed only for resolution of an acute condition or meeting a time
window (eg, for a prohibited medication). Only 1 rescreening per participant is permitted.
Rescreened participants must be assigned new participant numbers, undergo the informed consent
process, and then restart a new screening phase.
5.5. 
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 ≥100.4°F [38.0°C]) within 24 hours prior to the planned time of
vaccination.
An illness which in the judgment of the investigator may interfere with reactogenicityor safety
assessments.
Medically indicated vaccinations, including SARS-COV-2 vaccine boosters, taking into
account the restrictions outlined in Section 5.2., Exclusion Criteria, and Section 6.8.,
Concomitant Therapy.
If any of these events occur at the scheduled time for the first vaccination, randomization at a later
date within the screening period (allowed window up to 8 days) 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 delayed up to 10 days on top of the allowed time window of Visit 3 (±7 days).
The immunogenicity and safety assessments of Visit 3 should still be performed on the actual
Day 30 (±7 days).
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
36
Status: Approved, Date: 22 September 2023
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.
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.
6. 
STUDY VACCINATIONS AND CONCOMITANT THERAPY
6.1. 
Study Vaccinations Administered
Participants will be vaccinated according to the schedule detailed in the Schedule of Activities
(SoA). For description of the vaccinations, see below.
On Day 1, each participant will receive 2 IM injections, 1 in each arm; on Day 30, each participant
will receive 1 IM injection. The right arm should be used for seasonal influenza vaccination on
Day 1; the left arm should be used for ExPEC9V  or placebo vaccination on Days 1 and 30.
Two injections in the same deltoid are allowed only if medically indicated. If an injection cannot
be given in the deltoids due to a medical condition or other contraindication (for example, due to
the extent of tattoos which are felt to interfere with the examination of the injection site), use
alternative locations such as the hip, thigh or buttocks (to be avoided in overweight participants).
In all circumstances, IM injections in other locations than the upper arm 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, the decision regarding vaccination
will be assessed on a case-by-case basis, upon discussion between sponsor and investigator.
Study vaccination administration must be captured in the source documents and the eCRF.
VAC52416 (JNJ-78901563) will be manufactured and provided under the responsibility of the
sponsor. Refer to the IB for a list of excipients.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
37
Status: Approved, Date: 22 September 2023
Description of Vaccinations
Arm Name 
CoAd group (Group 1) 
Control group (Group 2)
Vaccination Name 
ExPEC9V + high-dose quadrivalent influenza vaccine 
(Day 1) followed by placebo (normal saline) (Day 30) 
Placebo (normal saline) + high-dose quadrivalent influenza
vaccine (Day 1) followed by ExPEC9V (Day 30)
Type 
Biological/Vaccine 
Biological/Vaccine
Dose Formulation 
Other 
Other
Solution for injection 
Solution for injection
Unit Dose Strength(s) 
ExPEC9V: 176 μg PS/mL 
Quadrivalent influenza vaccine: 240 µg (ie, 60 µg per 
strain) of haemagglutinin (HA) 
Normal saline: 9 mg/mL Sodium Chloride (0.9% w/v). 
ExPEC9V: 176 μg PS/mL
Quadrivalent influenza vaccine: 240 µg (ie, 60 µg per
strain) of haemagglutinin (HA)
Normal saline: 9 mg/mL Sodium Chloride (0.9% w/v).
Dosage Level(s) 
ExPEC9V - 0.5 mL single dose 
Quadrivalent influenza vaccine - 0.7 mL single dose 
Normal saline placebo - 0.5 mL single dose 
ExPEC9V - 0.5 mL single dose
Quadrivalent influenza vaccine - 0.7 mL single dose
Normal saline placebo - 0.5 mL single dose
Route of Administration 
IM  
IM
Use 
ExPEC9V: Experimental 
Quadrivalent influenza vaccine: Other 
Normal saline: Placebo comparator 
ExPEC9V: Experimental
Quadrivalent influenza vaccine: Other
Normal saline: Placebo comparator
Investigational Medicinal Product (IMP) 
Yes 
Yes
Sourcing 
Provided by the Sponsor 
Provided by the Sponsor
Packaging and Labeling 
Study intervention will be provided in a kit. Each kit 
will be labeled as required per country requirement 
Study intervention will be provided in a kit. Each kit will
be labeled as required per country requirement
Not in child resistant packaging 
Not in child resistant packaging
a Labels will contain information to meet the applicable regulatory requirements.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
38
Status: Approved, Date: 22 September 2023
6.2. 
Preparation/Handling/Storage/Accountability
Preparation/Handling/Storage of ExPEC9V and Placebo
All study vaccine must be stored at controlled temperatures in a secure location that can only be
accessed by authorized individuals. The study refrigerator/freezer must be equipped with a
continuous temperature monitor and alarm and should be equipped with back-up power systems.
If study vaccine is exposed to temperatures outside the specified temperature range, all relevant
data must 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.
Administration of study vaccine (ExPEC9V or placebo) on Days 1 and 30 will be blinded.
An unblinded study-site pharmacist, or other qualified individual will prepare the appropriate vials
and syringes, labeled with the participant’s identification number, and provide the syringes for
ExPEC9V and placebo in a blinded manner to the blinded vaccine administrator who will perform
the injection. The left arm should be used for ExPEC9V or placebo vaccination on Days 1 and 30.
Refer to the study Site Investigational Product Procedures Manual and/or the Investigational Product
Preparation and Administration Instructions for additional guidance on study vaccine preparation,
handling, storage and stability.
Preparation/Handling/Storage of High-dose Quadrivalent Seasonal Influenza Vaccine
HD quadrivalent seasonal influenza vaccine should be stored, handled, and administered according
to the instructions on the package insert. Administration of HD quadrivalent seasonal influenza
vaccine on Day 1 will not be blinded. The right arm should be used for seasonal influenza
vaccination on Day 1. The disposal of the vaccine will be according to local prescribing
information. The study refrigerator/freezer must be equipped with a continuous temperature
monitor and alarm and should be equipped with back-up power systems. If the vaccine is exposed
to temperatures outside the specified temperature range, all relevant data will be sent to the sponsor
to determine if the affected vaccine can be used or will be replaced. The affected vaccine must be
quarantined and not used until further instruction from the sponsor is received.
Accountability
The investigator is responsible for ensuring that all study vaccination  received at the site is
inventoried and accounted for throughout the study. The study vaccine administered to the
participant must be documented on the vaccine accountability form. All study vaccine will be
stored and disposed of according to the sponsor’s instructions.
Study vaccination 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 vaccination  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 vaccination will be documented on the vaccination return form. When the study site is an
authorized destruction unit and study vaccination supplies are destroyed on-site, this must also be
documented on the vaccination return form.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
39
Status: Approved, Date: 22 September 2023
Potentially hazardous materials such as used ampules, needles, syringes, and vials, should be
disposed of immediately in a safe manner and therefore will not be retained for vaccination
accountability purposes.
Study vaccination 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 vaccination will be
supplied only to participants participating in the study. Returned study vaccination must not be
dispensed again, even to the same participant. Study vaccination  may not be relabeled or
reassigned for use by other participants. The investigator agrees neither to dispense the study
vaccination 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 vaccinations are
provided in the Investigational Product Preparation Instructions and Study Site Investigational
Product and Procedures Manual.
6.3. 
Measures to Minimize Bias: Randomization and Blinding
Vaccination Allocation
Procedures for Randomization and Stratification
Central randomization will be implemented in this study. Participants will be randomly assigned
in a 1:1 ratio to 1 of2 vaccination groups based on a computer-generated randomization schedule
prepared before the study by or under the supervision of the sponsor. The randomization will be
balanced by using randomly permuted blocks and will be stratified by age category  (≥65 to
<75 years, ≥75 years) and history of UTI (yes/no).
The IWRS will assign a unique vaccination code, which will dictate the vaccination assignment
and matching study vaccination 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.
Participants who withdraw will not be replaced.
Blinding
The investigator will not be provided with randomization codes until database lock of the final
analysis. The participants remain blinded until database lock of the final analysis. The codes will
be maintained within the IWRS, which has the functionality to allow the investigator to break the
blind for an individual participant.
For the sponsor, unblinding (at the participant level) will occur at the time of the primary analysis
(Section 9.5., Interim Analysis). From the primary analysis onwards, group level results may be
shared as needed; however, efforts will be made to preserve the blinding to the individual
participant allocation.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
40
Status: Approved, Date: 22 September 2023
Data that may potentially unblind the study vaccine assignment (eg, immunogenicity data, study
vaccine preparation/accountability data, study vaccine allocation) 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 investigator may, in an emergency, determine the identity of the study vaccine by contacting
the IWRS. While the responsibility to break the study vaccine allocation code in emergency
situations resides solely with the investigator, it is recommended that the investigator contacts 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 must be documented by the IWRS, in the appropriate section
of the eCRF, and in the source document. The documentation received from the IWRS indicating
the code break must be retained with the participant’s source documents in a secure manner.
The study-site pharmacist or qualified individual with primary responsibility for study vaccine
preparation and dispensing will be unblinded to study vaccine allocation.
Note: administration of HD quadrivalent seasonal influenza vaccine will not be blinded.
Participants who have had their study vaccine assignment unblinded should continue to return for
scheduled evaluations.
6.4. 
Study Vaccination Compliance
Study vaccines will be administered IM by qualified study-site personnel. Details of each
administration will be recorded in the eCRF (including date, time, and site of injection).
6.5. 
Dose Modification
Not applicable.
6.6. 
Continued Access to Study Vaccination After the End of the Study
No continued access will be proposed for this study as all participants in this study will receive
ExPEC9V and HD quadrivalent seasonal influenza vaccine, irrespective of the study group to
which they are randomized. Therefore, there is no need to offer active study vaccine to placebo
recipients after the end of the study.
Participants will be instructed that study vaccination will not be made available to them after they
have completed/discontinued study vaccination.
6.7. 
Treatment of Overdose
For this study, any dose ofExPEC9V (VAC52416 (JNJ-78901563)) or HD quadrivalent seasonal
influenza vaccine greater than  the protocol-specified dose will be considered an overdose.
The sponsor does not recommend specific treatment for an overdose.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
41
Status: Approved, Date: 22 September 2023
In the event of an overdose, the investigator or treating physician should:
Contact the Medical Monitor immediately.
Evaluate the participant to determine, in consultation with the Medical Monitor, whether study
vaccine should be interrupted.
Closely monitor the participant for AEs/MAAEs/SAEs until resolution.
Document the quantity of the excess dose as well as the duration of the overdosing in the
eCRF.
Report as a special reporting situation.
6.8. 
Concomitant Therapy
Disallowed Medication
Refer to Section 5.2., Exclusion Criteria for details on which medication is disallowed before the
first vaccination 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 vaccination.
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in
which disallowed medications are administered.
Any use of disallowed medication is to be recorded in the eCRF.
Recording of Prestudy and Concomitant Medication
Prestudy specific therapies such as analgesic/antipyretic medications and non-steroidal
anti-inflammatory drugs, corticosteroids, antihistamines, vaccinations, antivirals, and all
antibacterials (including antibiotics and urinary tract antiseptics) administered within 30 days
before the first study vaccination must be recorded at screening.
Concomitant therapies associated with solicited AEs will be collected by the participants in the
participant eDiary from the time of study vaccination through 14 days after each vaccination.
Concomitant therapies associated with unsolicited AEs will be collected and recorded in the eCRF
from the time of study vaccination through 29 days after each vaccination. Concomitant therapies
associated with SAEs and MAAEs will be collected and recorded in the eCRF from ICF signature
until 6 months after the last study vaccination.
Analgesic/antipyretic medications and non-steroidal anti-inflammatory drugs may be used
post-vaccination only in cases of medical need (eg, fever or pain) and their use must be
documented. Use of these medications as routine prophylaxis prior to study vaccination is
discouraged.
Information on concomitant use of herbal supplements or vitamins will not be collected.
Use of any experimental medication (including experimental vaccines other than the study
vaccine) during the study is not allowed.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
42
Status: Approved, Date: 22 September 2023
In order to avoid misinterpretation of adverse reactions and potential immune interference,
vaccination with licensed live attenuated vaccines is prohibited within 28 days before or after the
administration of the study vaccination. Vaccination with other licensed vaccines (not live)
(eg, COVID-19, tetanus, hepatitis A, hepatitis B, rabies) is prohibited within 14 days before or
after the administration of the study vaccine. If a vaccine is indicated in a post-exposure setting
(eg, rabies or tetanus), it must take priority over the study vaccine.
Vaccination with a vaccine authorized for emergency use (eg, EUA, CMA, or a similar program)
is permitted when given at least 28 days before or after administration of the study vaccine.
Use of systemic corticosteroids2, antineoplastic agents, and immunomodulating agents must be
documented until 29 days after the last study vaccination. Antineoplastic and immunomodulating
agents, eg, cancer chemotherapeutic agents or systemic corticosteroids, or radiotherapy are
prohibited until 29 days after the last study vaccination. If the use of systemic corticosteroids,
antineoplastic or immunomodulating agents or any therapy described in Exclusion Criterion 2
becomes medically indicated during the study for any participant, the sponsor should be notified.
7. 
DISCONTINUATION OF STUDY VACCINATION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL
7.1. 
Discontinuation of Study Vaccination
Study vaccinations 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
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.
The participant withdraws consent to receive further study vaccination
The investigator believes that for safety reasons or reactogenicity reasons (eg, AE/MAAE) it
is in the best interest of the participant to discontinue study vaccination.
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 reaction following vaccination, not
attributable to causes other than vaccination
SAE or other potentially life-threatening (Grade 4) event that is determined to be related to
study vaccine
Disallowed use of systemic corticosteroids, antineoplastic and immunomodulating agents or
radiotherapy as detailed in Section 5.2., Exclusion Criteria.
2 
Note: Ocular, topical, or inhaled steroids are allowed.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
43
Status: Approved, Date: 22 September 2023
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
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
Death
When a participant withdraws before study completion, the reason for withdrawal is to be
documented in the eCRF and in the source document. If the reason for withdrawal from the study
is withdrawal of consent then no additional assessments are allowed.
An early exit visit will be conducted for those participants who are unable to continue participation
in the study and withdraw from the study before Day 210, but who do not withdraw consent (see
Schedule of Activities (SoA)). Participants who wish to withdraw consent from participation in
the study will be offered an early exit visit (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 Appendix 2: 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.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
44
Status: Approved, Date: 22 September 2023
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.
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. 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.
8. 
STUDY ASSESSMENTS AND PROCEDURES
Overview
The Schedule of Activities (SoA) summarizes the frequency and timing of study visits and of
immunogenicity and safety measurements applicable to this study.
If multiple assessments are scheduled for the same timepoint, it is recommended that procedures
be performed in the following sequence: vital signs, other safety assessments, blood draws. 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/or in the eCRF.
At screening, participants will be specifically questioned regarding the medical history of UTI.
This includes any uncomplicated, complicated, or recurrent UTIs that were diagnosed by a
physician (or qualified healthcare provider) and that required antimicrobial therapy. The details
will be collected in the eCRF. Note: a history of isolated male accessory gland infections will not
be considered as a history of UTI.
Participants will be provided a thermometer (to measure body temperature), ruler (to measure local
injection site reactions), and participant eDiary to record body temperature and solicited local (at
injection site) and systemic signs and symptoms.
The eDiary includes instructions on how to capture the signs and symptoms and grading scales to
assess severity. The study staff is responsible for providing appropriate training to the participant
to avoid missing or incorrect data. The eDiary  will be reviewed by study personnel at visits
indicated in the Schedule of Activities (SoA). If the eDiary review is missed, the eDiary will be
reviewed during the following visit. If a participant misses a vaccination, the eDiary covering the
period after the missed vaccination does not have to be completed.
The total blood volume to be collected from each participant will be approximately 90 mL.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
45
Status: Approved, Date: 22 September 2023
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the
samples.
Visit Windows
Visit windows are provided in the Schedules of Activities.
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.
Note: In case any of the criteria for temporarily delaying study vaccine administration (see
Section 7.1., Discontinuation of Study Vaccination) are met at Visit 3 (Day 30), this visit would
need to be split into 2 visits. The administration of the second study vaccination can be delayed up
to 10 days on top of the allowed time window of Visit 3 (±7 days). The immunogenicity and safety
assessments of Visit 3 should still be performed on the actual Day 30 (±7 days).
Home Health Care and Telemedicine Visits
Home health care and telemedicine visits conducted via phone or video conference may be
implemented by or with approval from the sponsor and per the clinical judgment of the investigator,
where feasible and permissible by local policy, regulations (as applicable) for participants for
whom there is no safety concern.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the eCRF or laboratory
requisition form.
Refer to the Schedule of Activities (SoA) 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. Collection, handling, storage, and shipment of samples
must be under the specified, and where applicable, controlled temperature conditions as indicated
in the Laboratory Manual.
Study-Specific Materials
The investigator will be provided with the following supplies:
Investigator’s Brochure
SmPC Package Insert for HD Quadrivalent Seasonal Influenza Vaccine
Participant eDiary and instructions for use
Thermometer
Ruler (to measure diameter of any erythema and swelling)
Study Site Investigational Product and Procedures Manual
Investigational Product Preparation Instructions
Laboratory manual
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
46
Status: Approved, Date: 22 September 2023
Laboratory kits
Contact Information page(s)
Study protocol
IWRS manual
electronic data capture (eDC) Manual/eCRF completion guidelines
Wallet card
Sample ICF
8.1. 
Immunogenicity Assessments
Venous blood samples of approximately 30 mL will be collected for the determination of humoral
immune responses at the timepoints indicated in the Schedule of Activities (SoA). Sample
collection and processing will be performed by the study-site personnel according to current
versions of approved standard operating procedures.
For assessment of immunogenicity, serum IgG antibody levels elicited by ExPEC9V against each
of the 9 vaccine O-serotypes and the carrier protein EPA will be measured by a validated multiplex
ECL-based immunoassay. Additionally, functional antibodies will be evaluated by a validated
MOPA.
Antibody titers against influenza virus strains recommended by the WHO for use in 2023-2024 in
the Northern Hemisphere season will be measured using validated HI assays.
8.2. 
Safety Assessments
Safety assessments will include the monitoring of AEs, MAAEs, physical examinations, and vital
signs.
AEs and MAAEs will be reported and followed by the investigator as specified in Section 8.3.,
Adverse Events, Medically-attended Adverse Events, Serious Adverse Events, and Other Safety
Reporting and Appendix 3: Adverse Events, Serious Adverse Events, Medically-attended Adverse
Events, Product Quality Complaints, and Other Safety Reporting: Definitions and Procedures for
Recording, Evaluating, Follow-up, and Reporting.
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, or until
the participant has been deemed lost to follow-up after demonstration of due diligence of follow-
up effort.
The study will include the following evaluations of safety and reactogenicity according to the time
points provided in the Schedule of Activities (SoA).
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
47
Status: Approved, Date: 22 September 2023
8.2.1. 
Physical Examinations
A general physical examination including body weight and height will be performed at screening.
It is at the investigator’s discretion how detailed the examination (which body systems are to be
covered) is deemed needed.
At any other visit, a targeted (abbreviated and symptom-directed) examination may be performed
if deemed necessary by the investigator based on any clinically relevant issues, clinically relevant
symptoms, and medical history.
Physical examinations will be performed by the investigator or appropriately trained delegate. 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. 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 measured pre- and postdose at each vaccination visit (Days 1 and 30). At
non-vaccination visits, vital signs will be measured if deemed necessary by the investigator. Body
temperature (oral route preferred), heart rate (beats per minute), respiratory rate (breaths per
minute), and systolic and diastolic blood pressure (mmHg) will be assessed. Height and weight
will be measured during screening.
Blood pressure and heart rate measurements will be assessed, if possible, with a completely
automated device. Manual techniques will be used only if an automated device is not available.
Sitting systolic and diastolic blood pressure and heart and respiratory rate measurements should
be preceded by at least 5 minutes of rest in a quiet setting without distractions (eg, television, cell
phones).
Confirmatory vital signs measurement can be performed if inconsistent with a prior measurement.
Any abnormalities or changes in severity noted during the review of vital signs should be
documented in the eCRF.
Participants will utilize an eDiary to record body temperature measurements post-vaccination (see
Section 8., Study Assessments and Procedures).
8.3. 
Adverse Events, Serious Adverse Events, Medically-attended Adverse
Events, and Other Safety Reporting
Timely, accurate, and complete reporting and analysis of safety information, including AEs, SAEs,
MAAEs, and PQCs, 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 information; all clinical studies conducted by the sponsor or its
affiliates will be conducted in accordance with those procedures.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
48
Status: Approved, Date: 22 September 2023
AEs and MAAEs 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.
Further details on AEs, MAAEs, SAEs, and PQCs can be found in Appendix 3: Adverse Events,
Serious Adverse Events, Medically-attended Adverse Events, Product Quality Complaints, and
Other Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up, and
Reporting.
8.3.1. 
Time Period and Frequency for Collecting Adverse Event,
Medically-attended Adverse Events, and Serious Adverse Event
Information
AEs, MAAEs, and SAEs will be collected as indicated in the Schedule of Activities (SoA).
All Adverse Events
AEs 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 moment of first vaccination will be collected on the Medical History eCRF page as
pre-existing conditions.
Solicited AEs, collected through an eDiary, will be recorded for each vaccination from the time of
vaccination until 14 days post-vaccination.
All unsolicited AEs and special reporting situations will be collected for each vaccination from the
time of vaccination until 29 days post-vaccination. Unsolicited AEs with the onset date outside the
timeframe defined above (>29 days after previous study vaccination), which are ongoing on the
day of the subsequent vaccination, should be recorded as such.
Serious Adverse Events and Adverse Events Leading to Discontinuation
All SAEs and AEs leading to discontinuation from the study/vaccination 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.
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 and Safety Report Form of the eCRF, which must be completed and reviewed by a physician
from the study site, and transmitted to the sponsor immediately but no later than within 24 hours.
The initial and follow-up reports of an SAE should be transmitted electronically or by facsimile
(fax).
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Status: Approved, Date: 22 September 2023
Medically-attended Adverse Events
MAAEs are defined as AEs with medically-attended visits including hospital, emergency room,
urgent care clinic, or other visits to or from medical personnel for any reason. Adverse events
(eg, abnormal vitals) identified at a routine study visit will not be considered MAAEs. Routine
medical visits for chronic comorbidities (or study visits) will not be considered medically-attended
visits.
All MAAEs 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.
8.3.2. 
Method of Detecting Adverse Events, Medically-attended Adverse
Events, and Serious Adverse Events
Care will be taken not to introduce bias when detecting AEs, MAAEs, 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 injection site) and systemic events for which the participant is specifically questioned and
which are noted by participants in their eDiary.
After each vaccination, participants will be observed for at least 30 minutes for presence of any
acute reactions and solicited events.
In addition, participants will record solicited signs and symptoms in an  eDiary for 14 days
post-vaccination. All participants will be provided with an  eDiary and instructions on how to
complete the eDiary (see Overview in Section 8., Study Assessments and Procedures). Electronic
diary information will be transferred from the eDiary source to the sponsor. Review of eDiary
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. Once a solicited sign
or symptom from an eDiary is considered to be of severity Grade 1 or above, it will be recorded
as a solicited AE.
Solicited Injection Site (Local) Adverse Events
Participants will be asked to note in the eDiary  occurrences of injection site pain/tenderness,
erythema and swelling at the study vaccine injection site daily for 14 days post-vaccination (day
of vaccination and the subsequent 14 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 the 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 (oral route preferred) in the eDiary in the
evening of the day of vaccination, and then daily for the next 14 days approximately at the same
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Status: Approved, Date: 22 September 2023
time each day. If more 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 ≥100.4°F (38°C), as recorded in at
least one measurement (Marcy 2004).
Participants will also be instructed on how to note signs and symptoms in the eDiary on a daily
basis for 14 days post-vaccination (day of vaccination and the subsequent 14 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 in the
participant eDiary.
Medically-attended Adverse Events
MAAEs are AEs with medically-attended visits including hospital, emergency room, urgent care
clinic, or other visits to or from medical personnel for any reason. Adverse events (eg, abnormal
vitals) identified at a routine study visit will not be considered MAAEs. Routine medical visits for
chronic comorbidities (or study visits) will not be considered medically-attended visits.
8.3.3. 
Follow-up of Adverse Events, Medically-attended 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, MAAE or
SAE as fully as possible. This may include additional laboratory tests or investigations,
histopathological examinations, or consultation with other health care professionals.
AEs and the special reporting situation of pregnancy will be followed by the investigator as
specified in Appendix 3: Adverse Events, Serious Adverse Events, Medically-attended Adverse
Events, Product Quality Complaints, and Other Safety Reporting: 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 Independent Ethics
Committee/Institutional Review Board (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.
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Status: Approved, Date: 22 September 2023
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 within 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.
If a participant becomes pregnant during the study, a determination regarding study vaccination
discontinuation must be made by the investigator in consultation with the sponsor. Follow-up
information regarding the outcome of the pregnancy and any postnatal sequelae in the infant will
be required. If the partner of a male participant becomes pregnant during the study, follow-up
information regarding the outcome of the pregnancy and any postnatal sequelae in the infant will
be required upon the consent provided by the partner.
8.4. 
Pharmacokinetics
Not applicable.
8.5. 
Genetics and Pharmacogenomics
Not applicable.
8.6. 
Biomarkers
Not applicable.
8.7. 
Immunogenicity Assessments
See Section 8.1.
8.8. 
Medical Resource Utilization and 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 is
outlined below. Specific details will be provided in the SAP.
9.1. 
Statistical Hypotheses
For a description of the hypotheses, see Section 3., Objectives and Endpoints.
The study is successful if both below objectives are demonstrated:
non-inferiority of the humoral immune response to the 4 influenza vaccine strains after
concomitant administration of ExPEC9V and a HD quadrivalent seasonal influenza vaccine
versus the administration of a HD quadrivalent seasonal influenza vaccine administered alone,
AND
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Status: Approved, Date: 22 September 2023
non-inferiority of the humoral immune response against the O-serotype antigens after
concomitant administration of ExPEC9V and a HD quadrivalent seasonal influenza vaccine
versus the administration of ExPEC9V administered alone
Therefore, the following CIs will be calculated:
the 2-sided 95% CIs for the difference in log10-transformed HI antibody titers against each of
the 4 influenza vaccine strains at 29 days after the administration of the HD quadrivalent
seasonal influenza vaccine between the Control and the CoAd group, and
The 2-sided 95% CIs for the difference in log10-transformed O-serotype antibody titers against
each of the 9 O-serotypes at 29 days after the administration of ExPEC9V between the Control
and the CoAd group
Only if the upper bound of the 2-sided 95% CI for the GMT ratio (Control group/CoAd group) of
the HI antibody titers for each of the 4 vaccine strains and of the O-serotype antibody titers for
each of the 9 O-serotype antigens lies below 1.5, non-inferiority of co-administration versus
separate administration will be concluded for both vaccines (seasonal influenza vaccine and
ExPEC9V). If 1 or more confidence limits for the GMT ratio exceed 1.5, non-inferiority cannot
be concluded.
As both non-inferiority objectives should be demonstrated to have a successful study, no
multiplicity adjustment is needed.
9.2. 
Sample Size Determination
Sample size calculations are performed under the following assumptions:
No effect of co-administration of ExPEC9V and seasonal influenza vaccine on the immune
response against influenza as measured by HI antibody titers against the 4 influenza vaccine
strains at 29 days after the administration of influenza vaccine
A standard deviation of 0.5 at the log10 scale for HI antibody titers against the 4 influenza
vaccine strains at 29 days after the administration of influenza vaccine (with or without
ExPEC9V)
No effect of co-administration of ExPEC9V and seasonal influenza vaccine on the immune
response against the O-serotype antigens as measured by antibody titers against the
9 O-serotype antigens at 29 days after the administration of ExPEC9V
A standard deviation of 0.6 at the log10 scale for ExPEC9V antibody titers at 29 days after the
administration of ExPEC9V (with or without seasonal influenza vaccine)
A non-inferiority margin of 1.53
2-sided α of 5%
3 
Non-inferiority criteria based on FDA guidance for influenza vaccines (FDA 2007b).
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Status: Approved, Date: 22 September 2023
A total of 419 evaluable participants per group are needed to have 99.91% power to show
non-inferiority in HI antibody titers for 1 influenza vaccine strain and to have 98.88% power to
show non-inferiority in antibody titers against 1 O-serotype antigen. With this sample size, the
overall power to show non-inferiority in HI antibody titers against each of the 4 influenza vaccine
strains at 29 days after the administration of seasonal influenza vaccine as well as non-inferiority
in antibody titers against each of the 9 O-serotype antigens at 29 days after the administration of
ExPEC9V is at least 90% (see table below).
1 comparison 
All comparisons
Flu NI (SD=0.5) 
99.91%  
99.64% (4 comparisons)
ExPEC9V NI (SD=0.6) 
98.88% 
90.36% (9 comparisons)
Total 
> 90% power
To account for 10% exclusions from the per protocol set (see below for definitions of analysis
sets), drop-outs and missing samples, approximately 466 participants per group should be enrolled,
resulting in a total sample size of approximately 932 participants.
9.3. 
Participant Analysis Sets
Vaccination assignment will follow the as-treated principle.
For purposes of analysis, the following analysis sets are defined:
The Full Analysis (FA) Set will include all participants who received at least 1 study vaccination,
regardless of the occurrence of protocol deviations and vaccine type (seasonal influenza, ExPEC9
vaccine, or placebo). All safety and participant information analyses will be based on the FA Set.
The Per-protocol Influenza Immunogenicity (PPII) Set will include all randomized participants
who received the first study vaccination  (ExPEC9V  in combination with seasonal influenza
vaccine for the CoAd group and seasonal influenza vaccine alone for the Control group), and for
whom immunogenicity data are available for at least one of the influenza strains in the vaccine.
Samples taken after a participant experiences a major protocol deviation expected to impact the
immunogenicity outcomes will be excluded from the PPII analysis.
The Per-protocol ExPEC9V Immunogenicity (PPEI) Set will include all randomized participants
who received ExPEC9V in combination with seasonal influenza vaccine for the CoAd group and
ExPEC9Valone for the Control group and for whom O-antigen immunogenicity data are available.
Samples taken after a participant experiences a major protocol deviation expected to impact the
immunogenicity outcomes will be excluded from the PPEI analysis.
The list of major protocol deviations that would lead to elimination from the immunogenicity
analysis will be specified in the SAP or major protocol violation criteria document, which will be
finalized before database lock and unblinding.
The primary analysis set for analyses related to influenza immunogenicity is the PPII Set, the
primary analysis set for analyses related to O-antigen immunogenicity is the PPEI Set. As a
sensitivity analysis, key tables may also be based on the FA Set.
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Status: Approved, Date: 22 September 2023
9.4. 
Statistical Analyses
The SAP will be finalized prior to database lock of the primary analysis 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.
9.4.1. 
General Considerations
The primary analysis will be performed when all participants have completed the visit 29 days
after the second study vaccination or discontinued earlier.
The significance level (α) is 5% (2-sided). As both non-inferiority objectives should be
demonstrated to have a successful study and as no interim analyses before the primary analysis are
planned, no multiplicity adjustments are needed.
9.4.2. 
Participant Information
For all participants, demographic characteristics (eg, age, height, body weight, BMI, race, and
gender) and other baseline characteristics will be tabulated and summarized descriptively by group.
9.4.3. 
Immunogenicity Analyses
The primary immunogenicity objectives will be assessed by calculating:
The 2-sided 95% CIs for the difference in log10-transformed HI antibody titers against each
of the 4 influenza vaccine strains at 29 days after the administration of the HD quadrivalent
seasonal influenza vaccine between the Control and the CoAd group.
The 2-sided 95% CIs for the difference in log10-transformed O-serotype antibody titers against
each of the 9 O-serotypes at 29 days after the administration of ExPEC9Vbetween the Control
and the CoAd group.
For HI antibody titers against each of the 4 influenza vaccine strains and for O-serotype antibody
titers against each of the 9 O-serotypes, an ANOVA model will be fitted with the respective titers
as dependent variable and group (Control or CoAd), age category, and history of UTI (as stratified)
as independent variables. Based on these ANOVA models, the CIs around the difference will be
calculated and will be back-transformed (by exponentiation) to CIs around a GMT ratio
(GMTControl group/GMTCoAd group) and compared to the non-inferiority limit of 1.5.
Only if the upper bound of the 2-sided 95% CI for the GMT ratio (Control group/CoAd group) of
the HI antibody titers for each of the 4 vaccine strains and of the O-serotype antibody titers for
each of the 9 O-serotype antigens lies below 1.5, non-inferiority of co-administration versus
separate administration will be concluded for both vaccines (seasonal influenza vaccine and
ExPEC9V). If 1 or more confidence limits for the GMT ratio exceed 1.5, non-inferiority cannot
be concluded.
As a sensitivity analysis to assess the impact of baseline titers, the primary endpoint will also be
evaluated adjusting for the respective baseline titers. For immunogenicity, baseline is considered
as the last assessment prevaccination. In a second sensitivity analysis, different variances between
the groups will be allowed. Therefore, the CIs will be calculated via Welch’s ANOVA.
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Status: Approved, Date: 22 September 2023
Seroconversion is defined for each of the 4 influenza vaccine strains at 29 days after the
administration of a seasonal influenza vaccine as:
HI titer ≥1:40 in participants with a prevaccination HI titer of <1:10, or
a ≥4-fold HI titer increase in participants with a prevaccination HI titer of ≥1:10
Seroprotection is defined for each of the 4 influenza vaccine strains as HI titer ≥1:40 at 29 days
after the administration of a seasonal influenza vaccine.
The difference in proportions of seroconverted and seroprotected participants between the Control
and the CoAd group will be estimated together with the 2-sided 95% CIs (calculated using
Wilson’s score method).
For ExPEC9V serotype antibodies as measured by multiplex ECL-based immunoassay and MOPA,
and EPA as measured by multiplex ECL-based immunoassay only, the following measures of
immunogenicity will be evaluated and tabulated by the study vaccination groups, for all
immunogenicity timepoints:
proportion of participants with a ≥2-fold and ≥4-fold increase in serum antibody titers from
prevaccination to 29 days after the administration of ExPEC9V
geometric mean titer
geometric mean of fold change from prevaccination, calculated from the 29-days
post-vaccination/prevaccination value.
Graphical representations of immunological parameters will be made as applicable.
9.4.4. 
Safety Analyses
No formal statistical testing of safety data is planned. All safety data will be analyzed descriptively
by group. All safety analyses will be made on the FA Set.
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). Any AE occurring at or after the initial
administration of study vaccination through the day of last dose plus 29 days is considered to be
treatment emergent. All reported treatment-emergent 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 vaccination group.
Summaries, listings, datasets, or participant narratives may be provided, as appropriate, for those
participants who die, who discontinue vaccination due to an AE, who experience a MAAE, or who
experience a severe or an SAE.
Summaries and/or listings may be provided separately for AEs with onset outside the above
defined timeframe (ie, beyond 29 days post-vaccination).
Solicited local (at injection site) and systemic AEs will be summarized descriptively. The number
and percentages of participants with at least one solicited local (at injection site) or systemic AE
will be presented. The frequencies by vaccine group as well as frequencies according to severity
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Status: Approved, Date: 22 September 2023
and duration will be described 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.
Vital Signs
Vital signs (systolic and diastolic blood pressure [sitting], heart rate, respiratory rate, and body
temperature) will be measured both before vaccination and after the end of the 30-minute
observation period.
Any clinically significant changes in vital signs will be reported as an AE. Any clinically
significant changes in vital signs that are observed prior to the first vaccination will be reported as
medical history.
Baseline and emerging vital signs abnormalities will be listed.
Physical Examinations
A full physical examination will be carried out at screening. At all other visits, a targeted
(abbreviated and symptom-directed) examination will be performed at the discretion of the
investigator, based on clinically relevant issues, clinically relevant symptoms and medical history.
Physical examination findings, including body weight, height, and body mass index, will be
summarized at baseline using descriptive statistics.
Any clinically significant abnormal findings are recorded as AE and will be analyzed as such.
9.5. 
Interim Analysis
No formal interim analysis is planned for this study.
The primary analysis will take place when all participants have performed their Day 59 visit or are
discontinued earlier. The primary analysis will include all available safety data and
immunogenicity results up to Day 59. The analysis will be performed based on sponsor unblinded
data.
The final analysis will include SAE data up to the end of the study and will be performed on
unblinded data.
The SAP will describe the planned analyses in greater detail.
9.6. 
Independent Data Monitoring Committee
An IDMC, will be established as noted in Committees Structure in  Section 10.2., Appendix 2:
Regulatory, Ethical, and Study Oversight Considerations. All IDMC members will be external and
independent of the sponsor, including at least one medical expert in the relevant therapeutic area
and at least one statistician. Safety issues that arise from this study will be reviewed by an IDMC
on an ad hoc basis, including all related SAEs and all fatal cases.
The IDMC responsibilities, authorities, and procedures will be provided in its charter.
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Status: Approved, Date: 22 September 2023
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Abbreviations and Definitions
AE 
adverse event
ANOVA  
analysis of variance
CI 
confidence interval
CMA  
Conditional Marketing Authorization
CoAd 
Co-administration
COVID-19 
Coronavirus Disease 2019
CRF  
case report form(s) (paper or electronic as appropriate for this study)
CRO  
contract research organization
CTM  
clinical trial manager
E. coli
Escherichia coli
ECL 
Electrochemiluminescent
eCRF  
electronic case report form
eDC  
electronic data capture
eDiary  
electronic diary
ELISA  
enzyme-linked immunosorbent assay
EUA  
Emergency Use Authorization
ExPEC  
extraintestinal pathogenic Escherichia coli
ExPEC10V  
10-valent extraintestinal pathogenic Escherichia coli vaccine
ExPEC4V  
4-valent extraintestinal pathogenic Escherichia coli vaccine
ExPEC9V  
9-valent extraintestinal pathogenic Escherichia coli vaccine
FA 
full analysis
FDA  
(United States) Food and Drug Administration
FOIA  
Freedom of Information Act
GLP  
Good Laboratory Practice
GMT  
geometric mean titer
HA  
Hemagglutinin
HBV  
hepatitis B virus
HCV  
hepatitis C virus
HD  
high-dose
HI 
hemagglutination inhibition
HI assay  
hemagglutination inhibition assay
HIV  
human immunodeficiency virus
IB  
Investigator’s Brochure
ICF  
informed consent form
ICH  
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for
Human Use
ICMJE 
International Committee of Medical Journal Editors
IDMC  
Independent Data Monitoring Committee
IEC  
Independent Ethics Committee
IED  
invasive extraintestinal pathogenic Escherichia coli disease
IgG  
immunoglobulin G
IM  
intramuscular(ly)
IMP  
Investigational Medicinal Product
IRB  
Institutional Review Board
IWRS  
interactive web response system
LTM  
local trial manager
MAAE 
medically-attended adverse event
MedDRA  
Medical Dictionary for Regulatory Activities
MOPA  
multiplex opsonophagocytic killing assay
NI 
non-inferiority
NZW  
New Zealand White
OHRP  
Office for Human Research Protections
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Status: Approved, Date: 22 September 2023
OPA  
opsonophagocytic killing assay
P. aeruginosa 
Pseudomonas aeruginosa
PCC  
protocol clarification communication
PCR  
Polymerase chain reaction
PPEI 
Per-protocol ExPEC9V Immunogenicity
PPII 
Per-protocol Influenza Immunogenicity
PQC  
Product Quality Complaint
PT  
preferred term
SAE 
serious adverse event
SAP  
statistical analysis plan
SARS-COV-2 
severe acute respiratory syndrome coronavirus 2
SD 
standard deviation
SUSAR  
suspected unexpected serious adverse reaction
US  
United States
UTI 
urinary tract infection
WHO  
World Health Organization
Definitions of Terms
eDiary  
The electronic technology used to record solicited signs and symptoms by the participants.
Home health visit 
A home visit by a healthcare professional in the event that the participant is unable to come
to the site.
Remote visit 
A visit for which collection of samples is not required and which will be conducted via
telephone call.
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Status: Approved, Date: 22 September 2023
10.2. Appendix 2: Regulatory, Ethical, and Study Oversight Considerations
10.2.1. 
Regulatory and Ethical Considerations
The term “sponsor” refers to the sponsor or its designee, as applicable.
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the
protocol, current ICH guidelines on Good Clinical Practice (GCP), and applicable regulatory and
country-or territory-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 Independent Ethics Committees/Institutional
Review Boards (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) involves 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 during the study, 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 must be made before implementing any departure from the protocol. In all
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Status: Approved, Date: 22 September 2023
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 CRF and source documents will reflect
any 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/territory, 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 vaccination
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
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Local laboratory documentation demonstrating competence and test reliability
(eg, accreditation/license), if applicable
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
vaccination
New information that may adversely affect the safety of the participants or the conduct of the
study
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Deviations from or changes to the protocol to eliminate immediate hazards to the participants
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/Territory Selection
This study will only be conducted in those countries/territories 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.
10.2.2. 
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 study and
for 1 year after completion of the study.
Refer to Required Prestudy Documentation (above) for details on financial disclosure.
10.2.3. 
Informed Consent Process
Each participant must give 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
must be in accordance with principles that originated in the Declaration of Helsinki, current ICH
and GCP guidelines, applicable regulatory requirements, and sponsor policy.
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,
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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 must 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.
10.2.4. 
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 information about, and where
required per applicable regulations, 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.
The informed consent also provides information to address the lawful transfer of the data to other
entities and to other countries/territories.
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, or make requests
concerning his or her personal data in accordance with applicable data protection law. Reasonable
steps 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
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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.
10.2.5. 
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 VAC52416 (JNJ-78901563), to
understand IED, to understand differential vaccination responders, and to develop tests/assays
related to VAC52416 (JNJ-78901563) and IED. The research may begin at any time during the
study or during 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).
10.2.6. 
Committees Structure
The IDMC membership, responsibilities, authorities, and procedures will be provided in its charter.
10.2.7. 
Publication Policy/Dissemination of Clinical Study Data
All information, including but not limited to information regarding VAC52416 (JNJ-78901563)
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  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 the goals of 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 VAC52416 (JNJ-78901563) 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
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study will be used to determine a coordinating investigator for the study. Results of exploratory
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 the 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.
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 interim results of clinical studies as required by law. The
disclosure of the study results will be performed after the end of study in order to ensure the
statistical analyses are relevant.
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Status: Approved, Date: 22 September 2023
10.2.8. 
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 CRF completion will be provided and reviewed with study-site personnel before
the start of the study. The sponsor may review the CRF for accuracy and completeness during on-
site monitoring visits and after transmission to the sponsor; any discrepancies will be resolved with
the 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.
10.2.9. 
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 the 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.
Data must be entered into the eCRF in English. The eCRF must be completed as soon as possible
after a participant visit and the forms must be available for review at the next scheduled monitoring
visit.
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.
10.2.10. 
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/MAAEs and follow-up of AEs/MAAEs; concomitant medication;
vaccination receipt/dispensing/return records; study vaccination administration information; and
date of study completion and reason for early discontinuation of study vaccination or withdrawal
from the study, if applicable.
The author of an entry in the source documents must be identifiable.
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The participant’s eDiary used to collect information regarding solicited signs and symptoms after
vaccination will be considered source data.
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).
The following data will be recorded directly into the eCRF and will be considered source data.
Race
Blood pressure and pulse/heart rate
Respiratory rate
Height and weight
Details of physical examination
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 CRF in the protocol include the
eSource system, but information collected through eSource may not be limited to that found in the
CRF.
10.2.11. 
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 may compare the data entered into the eCRF with the source documents
(eg, hospital/clinic/physician’s office medical records). 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.
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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.
There will be independent monitoring of the pharmacy and preparation of study vaccines by an
unblinded monitor (independent study vaccine monitor); regular monitors will be blinded.
10.2.12. 
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
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 must immediately notify the sponsor if he or she has been
contacted by a regulatory agency concerning an upcoming inspection.
10.2.13. 
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all CRF 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.
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10.2.14. 
Study and Site Start and Closure
First Act of Recruitment
The first participant screened is considered the first act of recruitment and it becomes the study
start date.
Study/Site 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.
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 intervention.
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 vaccination development
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Status: Approved, Date: 22 September 2023
10.3. Appendix 3: Adverse Events, Serious Adverse Events, Medically-attended
Adverse Events, Product Quality Complaints, and Other Safety Reporting:
Definitions and Procedures for Recording, Evaluating, Follow-up, and
Reporting
10.3.1. 
Adverse Event Definitions and Classifications
Adverse Event
An AE is any untoward medical occurrence in a clinical study participant administered a
pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have
a causal relationship with the study vaccination. 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 International
Council on Harmonisation [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 the time period of the 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.
Medically-attended Adverse Event
MAAEs are defined as AEs with medically-attended visits including hospital, emergency room,
urgent care clinic, or other visits to or from medical personnel for any reason. Adverse events
(eg, abnormal vitals) identified at a routine study visit will not be considered MAAEs. Routine
medical visits for chronic comorbidities (or study visits) will not be considered medically-attended
visits.
Serious Adverse Event
An  SAE based on ICH and 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 was 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*
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*Medical and scientific judgment must 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
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 vaccination 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).
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 VAC52416 (JNJ-78901563), the expectedness of an AE will be
determined by whether or not it is listed in the IB. For HD Quadrivalent Seasonal Influenza
Vaccine with a marketing authorization, the expectedness of an AE will be determined by whether
or not it is listed in the applicable product information sheet.
10.3.2. 
Attribution Definitions
Assessment of Causality
The causal relationship to study vaccination  is assessed by the investigator. The following
selection must be used to assess all AEs.
Related
There is a reasonable causal relationship between study vaccine administration and the AE.
Not Related
There is not a reasonable causal relationship between study vaccine 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 (local) will be considered related to the study
vaccine administration.
10.3.3. 
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 (US Dept Health 2007a), included in Appendix  5:
Toxicity Grading Scale.
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For AEs/MAAEs not identified in the grading table, the following guidelines will be applied:
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 ER visit or hospitalization
The severity of solicited signs and symptoms will be graded in the eDiary by the participant based
on the severity assessment provided in the eDiary and then verified by the investigator using the
toxicity grading scale in Appendix  5: Toxicity Grading Scale. (Note: severity of the measured
events will be derived from the diameter [for erythema and swelling] and the temperature
measurements [for fever]).
10.3.4. 
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 mustbe recorded in the CRF. Any special reporting
situation that meets the criteria of an SAE must be recorded on the SAE page of the CRF.
10.3.5. 
Procedures
All Adverse Events
All AEs and MAAEs, 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
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relationship of the AE or MAAE to study therapy. All measures required for AE and MAAE
management must be recorded in the source document and reported according to sponsor
instructions.
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 the
participant’s discontinuation from 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
participation in the 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 CRF).
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.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
74
Status: Approved, Date: 22 September 2023
10.3.6. 
Product Quality Complaint Handling
Definition
A product quality complaint (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, reliability or performance of a distributed product, including its labeling, drug delivery
system, or package integrity. A PQC may have an impact on the safety and efficacy of the product.
In addition, it includes any technical complaints, defined as any complaint that indicates a potential
quality issue during manufacturing, packaging, release testing, stability monitoring, dose
preparation, storage or distribution of the product or the drug delivery system.
Procedures
All initial PQCs must be reported to the sponsor by the study-site personnel within 24 hours after
being made aware of the event.
A sample of the suspected product should be maintained under the correct storage conditions until
a shipment request is received from the sponsor.
10.3.7. 
Contacting Sponsor Regarding Product Quality
The names (and corresponding telephone numbers) of the individuals who must be contacted
regarding safetyissues, PQC, or questions regarding the studyare listed in the Contact Information
page(s), which will be provided as a separate document.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
75
Status: Approved, Date: 22 September 2023
10.4. Appendix 4: Contraceptive Guidance
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
Appendix 3: Adverse Events, Serious Adverse Events, Medically-attended Adverse Events,
Product Quality Complaints, and Other Safety Reporting: Definitions and Procedures for
Recording, Evaluating, Follow-up, and Reporting.
Definitions
Female Participants Not of Childbearing Potential
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.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
76
Status: Approved, Date: 22 September 2023
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.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
77
Status: Approved, Date: 22 September 2023
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 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.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
78
Status: Approved, Date: 22 September 2023
Systemic Illness 
Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life
Threatening
(Grade 4)
Illness or clinical 
adverse event (as 
defined according to 
applicable 
regulations)
No interference with  
activity  
Some interference 
with activity not 
requiring medical 
intervention 
Prevents daily  
activity and
requires medical
intervention
Hospitalization#
# Revised by the sponsor.
B: Tables for Laboratory Abnormalities
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
CPK –mg/dL 
1.25 –1.5 x  
ULN***
1.6 –3.0 x ULN  3.1 –10 x ULN  
> 10 x ULN
Albumin –Hypoalbuminemia g/dL 
2.8 –3.1 
2.5 –2.7 
< 2.5 
--
Total Protein –Hypoproteinemia g/dL 
5.5 –6.0 
5.0 –5.4 
< 5.0 
--
Alkaline phosphate –increase by factor 
1.1 –2.0 x ULN 2.1 –3.0 x ULN 3.1 –10 x ULN > 10 x ULN
Liver Function Tests –ALT, AST  
increase by factor
1.1 –2.5 x ULN  2.6 –5.0 x ULN  5.1 –10 x ULN  > 10 x ULN
Bilirubin –when accompanied by any 
increase in Liver Function Test increase 
by factor
1.1 –1.25 x 
ULN  
1.26 –1.5 x 
ULN  
1.51 –1.75 x 
ULN
> 1.75 x ULN
Bilirubin –when Liver Function Test is 
normal; increase by factor
1.1 –1.5 x ULN  1.6 –2.0 x ULN  2.0 –3.0 x ULN  > 3.0 x ULN
Cholesterol 
201 –210 
211 –225 
> 226 
---
Pancreatic enzymes –amylase, lipase 
1.1 –1.5 x ULN 1.6 –2.0 x ULN 2.1 –5.0 x ULN > 5.0 x ULN
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
79
Status: Approved, Date: 22 September 2023
* 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 ifthe
participant had a new seizure associated with the low sodium value.
***ULN is the upper limit ofthe 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 – 
124,999
25,000 –99,999 
< 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 ofthe normal range.
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.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
80
Status: Approved, Date: 22 September 2023
10.6. Appendix 6: Specific Criteria for the Inclusion of Potential Participants
with Chronic Stable HIV, HCV, or HBV Infection
The following guidelines should be used to consider for inclusion potential participants with
chronic stable HIV, HCV, or HBV infection. If a potential participant does not have relevant
laboratory results pertaining to HIV infection in his/her medical records from the last 6 months
before screening, they will be instructed to go to their local health care provider and obtain the
necessary data for potential entry into the trial. Potential participants will not be screened for
laboratory evidence of HIV, HCV, or HBV infection. For a potential participant with a medical
history of HCV or HBV infection, the below guidelines regarding stable infection are intended to
inform the investigator's judgment of eligibility, but the availability of all the listed laboratory data
in the medical records is not mandatory.
1. Stable/well-controlled HIV infection includes:
a. CD4 cell count ≥300 cells/µL.
b. HIV viral load <50 copies/mL.
c. Participant must be on stable anti-retroviral treatment (ART) for 6 months (unless the
change is due to tolerability, in which case the regimen can be for only the previous
3 months; changes in formulation are allowed; nationwide guidelines that require
transition from one ART regimen to another are allowed) and the participant must be
willing to continue his/her ART throughout the study as directed by his/her local
physician.
Note: Participants with ongoing and progressive comorbidities associated with HIV infection will
be excluded but comorbidities associated with HIV infection that have been clinically stable for
the past 6 months are not an exclusion criterion.
Laboratory methods for confirming a diagnosis of HIV infection are: Any evidence (historic or
current) from medical records, such as ELISA with confirmation with Western Blot or PCR, or of
a detectable viral load (country-specific regulatory approved tests).
2. Stable known HCV infection:
History of chronic HCV with evidence of sustained virological response (defined as
undetectable HCV RNA) for ≥12 weeks following HCV treatment or without evidence of
HCV RNA viremia (undetectable HCV viral load).
3. Stable known HBV infection:
May be defined as presence of hepatitis B surface antigen for ≥6 months and:
a. HBeAg negative, anti-HBe positive, and/or
b. Serum HBV DNA <2,000 IU/mL; and
c. No other findings indicating active inflammatory process in liver.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
81
Status: Approved, Date: 22 September 2023
10.7. Appendix 7: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located
directly before the Table of Contents (TOC).
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
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CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
82
Status: Approved, Date: 22 September 2023
11. 
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Al-Hasan MN (2009b), Lahr BD, Eckel-Passow JE, Baddour LM. Seasonal variation in Escherichia coli
bloodstream infection: a population-based study. Clin Microbiol Infect. 2009:15;947-950.
De Kraker ME (2013), Jarlier V, Monen JC, et al. The changing epidemiology of bacteraemias in Europe: trends
from the European Antimicrobial Resistance Surveillance System. Clin Microbiol Infect. 2013:19;860-868.
Gidudu JK (2012), Walco GA, Taddio A, et al. Immunization site pain: Case definition and guidelines for
collection, analysis, and presentation of immunization safety data. Vaccine. 2012;30(30):4558-4577.
Investigator’s Brochure: VAC52416 (ExPEC 10-valent vaccine / 9-valent vaccine). Edition 2. Janssen Research &
Development (08 April 2022).
Johnson JR (2003), Gajewski A, Lesse AJ, Russo TA. Extraintestinal pathogenic Escherichia coli as a cause of
invasive nonurinary infections. J Clin Microbiol. 2003:41;5798-5802.
Kohl KS (2007), Walop W, Gidudu J, et al. Swelling at or near injection site: Case definition and guidelines for
collection, analysis, and presentation of immunization safety data. Vaccine. 2007;25(31):5858-5874.
Laupland KB (2014), Church DL. Population-based epidemiology and microbiology of community-onset
bloodstream infections. Clin Microbiol Rev. 2014;27;647-664.
Marcy SM (2004), Kohl KS, Dagan R, et al. Fever as an adverse event following immunization: case definition and
guidelines of data collection, analysis, and presentation. Vaccine. 2004;22(5-6):551-556.
Synoptic Clinical Study Report 63871860BAC2001. Randomized, Double-blind, Placebo-controlled, Multicenter
Phase 2 Study in Healthy Adults to Evaluate the Safety and Immunogenicity of Different Doses of JNJ-63871860
(long term follow up [Year 3] analysis). Janssen Research & Development. 24 Mar 2020.
US Department of Health and Human Services (2007a), Food and Drug Administration, Center for Biologics
Evaluation and Research. Guidance for Industry. Toxicity Grading Scale for Healthy Adult and Adolescent
Volunteers Enrolled in Preventive Vaccine Clinical Trials. Available at:
https://www.fda.gov/media/73679/download. Accessed 13 December 2022.
US Department of Health and Human Services (2007b), Food and Drug Administration. Clinical Data Needed to
Support the Licensure of Seasonal Inactivated Influenza Vaccines. Available at:
https://www.fda.gov/media/73706/download. Accessed 19 January 2023.
US Department of Health and Human Services (1998), Office for Human Research Protections. OHRP Expedited
Review Categories. Available at: http://www.hhs.gov/ohrp/regulations-and-policy/guidance/categories-of-research-
expedited-review-procedure-1998/index.html. Accessed 13 December 2022.
US Food and Drug Administration (1998). 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 13 December 2022.
Williamson DA (2013), Lim A, Wiles S, Roberts SA, Freeman JT. Population-based incidence and comparative
demographics of community-associated and healthcare-associated Escherichia coli bloodstream infection in
Auckland, New Zealand, 2005-2011. BMC Infect Dis. 2013:13;385.
NCT06134804

VAC52416 (JNJ-78901563) ExPEC9V
Clinical Protocol VAC52416BAC3002 Amendment 1
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
83
Status: Approved, Date: 22 September 2023
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 vaccine, 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 Vaccines & Prevention B.V.
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 course of the study, written
notification will be provided by the investigator to the sponsor, and a protocol amendment will not be required.
PPD
NCT06134804

Signature
User 
Date 
Reason
 
22-Sep-2023
08:40:24
(GMT)
Document Approval
PPD
NCT06134804