A Phase 2 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of a Heterologous 2-dose Vaccination Regimen Using Ad26.ZEBOV and MVA-BN®-Filo in Infants Aged 4-11 Months in Guinea and Sierra Leone
Phase: PHASE2
Conditions: Ebola Virus Disease
Sponsor: Janssen Vaccines & Prevention B.V.

CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
1
Status: Approved,Date: 28 September 2021
Janssen Vaccines & Prevention B.V. *
Clinical Protocol
A Phase 2 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of a
Heterologous 2-dose Vaccination Regimen Using Ad26.ZEBOV and MVA-BN®-Filo in
Infants Aged 4-11 Months in Guinea and Sierra Leone
Protocol VAC52150EBL2005; Phase 2
AMENDMENT 4
Innovative Medicines Initiative-2
EBOVAC3Consortium Partners
(London School of Hygiene and Tropical Medicine,
Institut National de la Santé et de la Recherche Médicale,
University of Antwerp,
College of Medicine and Allied Health Sciences,
and Janssen Vaccines & Prevention B.V.)
VAC52150  (Ad26.ZEBOV, MVA-BN-Filo [MVA-mBN226B])
*Janssen Vaccines & Prevention B.V. is a Janssen pharmaceutical company of Johnson & Johnson and is
hereafter referred to as the sponsor of the study. The sponsor is identified on the Contact Information page
that accompanies the protocol.
Status: 
Approved
Date: 
28 September 2021
Prepared by: Janssen Vaccines & Prevention B.V.
EDMS number: 
EDMS-ERI-171651296, 15.0
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.
NCT03929757

VAC52150 (Ad26.ZEBOV, MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol Amendment 4VAC52150EBL2005
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Status: Approved,Date: 28 September 2021
TABLE OF CONTENTS
TABLE OF CONTENTS............................................................................................................................... 2
LIST OF ATTACHMENTS............................................................................................................................ 4
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 4
PROTOCOL AMENDMENTS....................................................................................................................... 5
SYNOPSIS.................................................................................................................................................. 10
TIME AND EVENTS SCHEDULE .............................................................................................................. 15
ABBREVIATIONS...................................................................................................................................... 20
DEFINITIONS OF TERMS.......................................................................................................................... 21
1. 
INTRODUCTION................................................................................................................................ 22
1.1. 
Background.................................................................................................................................... 22
1.2. 
Active Comparator Vaccine ........................................................................................................... 26
1.3. 
Benefit/Risk Section....................................................................................................................... 26
1.3.1. 
Known Benefits........................................................................................................................... 26
1.3.2. 
Potential Benefits........................................................................................................................ 26
1.3.3. 
Known Risks............................................................................................................................... 27
1.3.4. 
Potential Risks............................................................................................................................ 27
1.3.5. 
Overall Benefit/Risk Assessment ............................................................................................... 29
1.4. 
Overall Rationale for the Study...................................................................................................... 30
2. 
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS........................................................................... 31
2.1. 
Objectives and Endpoints .............................................................................................................. 31
2.2. 
Hypothesis ..................................................................................................................................... 32
3. 
STUDY DESIGN AND RATIONALE................................................................................................. 32
3.1. 
Overview of Study Design.............................................................................................................. 32
3.1.1. 
Main Study.................................................................................................................................. 32
3.1.2. 
Extension Phase......................................................................................................................... 35
3.2. 
Study Design Rationale.................................................................................................................. 35
4. 
PARTICIPANT POPULATION .......................................................................................................... 36
4.1. 
Main Study..................................................................................................................................... 36
4.1.1. 
Inclusion Criteria......................................................................................................................... 36
4.1.2. 
Exclusion Criteria........................................................................................................................ 37
4.2. 
Extension Phase ............................................................................................................................ 39
4.2.1. 
Inclusion Criteria......................................................................................................................... 39
4.2.2. 
Exclusion Criteria........................................................................................................................ 40
4.3. 
Prohibitions and Restrictions ......................................................................................................... 41
5. 
INTERVENTION ALLOCATION AND BLINDING ............................................................................ 42
6. 
DOSAGE AND ADMINISTRATION .................................................................................................. 43
6.1. 
Criteria for Postponement of Vaccination ...................................................................................... 45
6.2. 
Contraindications to Second Vaccination and 6-months Post-dose-2 Vaccination....................... 45
7. 
INTERVENTION COMPLIANCE....................................................................................................... 46
8. 
PRESTUDY AND CONCOMITANT THERAPY ................................................................................ 46

VAC52150 (Ad26.ZEBOV, MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol Amendment 4VAC52150EBL2005
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Approved, Date: 28 September 2021
9. 
STUDY EVALUATIONS.................................................................................................................... 47
9.1. 
Study Procedures........................................................................................................................... 47
9.1.1. 
Overview..................................................................................................................................... 47
9.1.2. 
Screening Period........................................................................................................................ 48
9.1.3. 
Vaccination Period...................................................................................................................... 49
9.1.4. 
Follow-up Period......................................................................................................................... 50
9.2. 
Procedures in Case of a Study Pause........................................................................................... 50
9.3. 
Safety Evaluations ......................................................................................................................... 51
9.3.1. 
Safety Assessments ................................................................................................................... 51
9.3.2. 
Study Pausing Rules .................................................................................................................. 53
9.4. 
Immunogenicity Assessments ....................................................................................................... 55
9.5. 
Sample Collection and Handling.................................................................................................... 55
10. PARTICIPANT COMPLETION/DISCONTINUATION OF STUDY INTERVENTION/
WITHDRAWAL FROM THE STUDY................................................................................................. 56
10.1. 
Completion ..................................................................................................................................... 56
10.2. 
Discontinuation of Study Intervention/Withdrawal From the Study................................................ 56
11. STATISTICAL METHODS................................................................................................................. 58
11.1. 
Analysis Sets.................................................................................................................................. 58
11.2. 
Sample Size Determination ........................................................................................................... 58
11.3. 
Participant Information ................................................................................................................... 59
11.4. 
Safety Analyses ............................................................................................................................. 59
11.5. 
Immunogenicity Analyses .............................................................................................................. 60
11.6. 
Interim Analysis.............................................................................................................................. 60
11.7. 
Independent Data Monitoring Committee ...................................................................................... 60
11.8. 
Independent Medical Reviewer...................................................................................................... 60
12. ADVERSE EVENT REPORTING ...................................................................................................... 61
12.1. 
Definitions ...................................................................................................................................... 61
12.1.1. 
Adverse Event Definitions and Classifications ........................................................................... 61
12.1.2. 
Attribution Definitions.................................................................................................................. 63
12.1.3. 
Severity Criteria .......................................................................................................................... 63
12.2. 
Special Reporting Situations.......................................................................................................... 64
12.3. 
Procedures..................................................................................................................................... 64
12.3.1. 
All Adverse Events...................................................................................................................... 64
12.3.2. 
Serious Adverse Events ............................................................................................................. 65
12.3.2.1. 
Thrombosis with Thrombocytopenia Syndrome...................................................................... 66
12.4. 
Contacting Sponsor Regarding Safety........................................................................................... 67
13. PRODUCT QUALITY COMPLAINT HANDLING.............................................................................. 67
13.1. 
Procedures..................................................................................................................................... 67
13.2. 
Contacting Sponsor Regarding Product Quality............................................................................ 68
14. STUDY INTERVENTION INFORMATION ........................................................................................ 68
14.1. 
Physical Description of Study Intervention..................................................................................... 68
14.1.1. 
Ad26.ZEBOV .............................................................................................................................. 68
14.1.2. 
MVA-BN-Filo............................................................................................................................... 68
14.1.3. 
MenACWY.................................................................................................................................. 68
14.2. 
Packaging ...................................................................................................................................... 68
14.3. 
Labeling.......................................................................................................................................... 69
14.4. 
Preparation, Handling, and Storage............................................................................................... 69
14.5. 
Intervention Accountability............................................................................................................. 69
15. STUDY-SPECIFIC MATERIALS....................................................................................................... 70
16. ETHICAL ASPECTS......................................................................................................................... 70
16.1. 
Study-specific Design Considerations ........................................................................................... 70

VAC52150 (Ad26.ZEBOV, MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol Amendment 4VAC52150EBL2005
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Approved, Date: 28 September 2021
16.2. 
Regulatory Ethics Compliance....................................................................................................... 71
16.2.1. 
Investigator Responsibilities....................................................................................................... 71
16.2.2. 
Independent Ethics Committee or Institutional Review Board................................................... 72
16.2.3. 
Informed Consent ....................................................................................................................... 73
16.2.4. 
Privacy of Personal Data ............................................................................................................ 74
16.2.5. 
Long-term Retention of Samples for Additional Future Research.............................................. 74
17. ADMINISTRATIVE REQUIREMENTS.............................................................................................. 75
17.1. 
Protocol Clarification Communications .......................................................................................... 75
17.2. 
Protocol Amendments.................................................................................................................... 75
17.3. 
Regulatory Documentation ............................................................................................................ 76
17.3.1. 
Regulatory Approval/Notification ................................................................................................ 76
17.3.2. 
Required Prestudy Documentation............................................................................................. 76
17.4. 
Subject Identification, Enrollment, and Screening Logs ................................................................ 77
17.5. 
Source Documentation................................................................................................................... 77
17.6. 
Case Report Form Completion ...................................................................................................... 78
17.7. 
Data Quality Assurance/Quality Control ........................................................................................ 78
17.8. 
Record Retention ........................................................................................................................... 79
17.9. 
Monitoring ...................................................................................................................................... 79
17.10. Study Completion/Termination....................................................................................................... 80
17.10.1. Study Completion/End of Study.................................................................................................. 80
17.10.2. Study Termination....................................................................................................................... 80
17.11. On-site Audits................................................................................................................................. 80
17.12. Use of Information and Publication ................................................................................................ 81
18. COVID-19 APPENDIX: GUIDANCE ON STUDY CONDUCT DURING THE COVID-19
PANDEMIC........................................................................................................................................ 83
REFERENCES............................................................................................................................................ 84
INVESTIGATOR AGREEMENT................................................................................................................. 93
LIST OF ATTACHMENTS
Appendix 1: 
Test of Understanding....................................................................................................... 86
Appendix 2: 
Toxicity Grading Scale for Healthy Pediatric Participants up to 3 Years of Age
Enrolled in Preventive Vaccine Clinical Trials .......................................................................... 88
Appendix 3: 
Thrombotic Events to be Reported................................................................................... 92
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Frequency of Solicited and Unsolicited Adverse Events in Children and Adolescents
From Studies EBL2002 and EBL3001 –Blinded Data............................................................. 25
Table 2: 
Study Vaccination Schedule (Main Study)................................................................................ 43
Table 3: 
Probability of Observing at Least One Adverse Event Given a True Adverse Event
Incidence................................................................................................................................... 59
FIGURES
Figure 1: Schematic Overview of the Main Study.................................................................................... 34

VAC52150 (Ad26.ZEBOV, MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol Amendment 4VAC52150EBL2005
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Approved, Date: 28 September 2021
PROTOCOL AMENDMENTS
Protocol Version 
Date
Amendment 4 
This document
Amendment 3 
06 August 2020
Amendment 2 
01 October 2019
Amendment 1 
07 March 2019
Original Protocol 
06 December 2018
Amendments below are listed beginning with the most recent amendment.
Amendment 4 (This document)
The overall reason for the amendment: The overall reason for the amendment is to offer participants enrolled in
the control arm the possibility to receive the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen.
Rationale: Per the protocol amendment 3 dated 6 August 2020: “Upon completion of the study, sites may offer the
Ad26.ZEBOV, MVA BN Filo vaccine (if licensed and/or WHO prequalified) to the control arm upon consultation
with the health authorities.” The current protocol Amendment 4 describes the extension of the study for participants
originally enrolled in the control arm who consent to receiving the Ebola vaccine regimen. The extension phase
will consist of a screening, vaccination,and safety follow-up phase until 28 days post-dose 2. The primary interim
analysis for the blinded phase of the study will be done when all participants have completed the 12 months post-
dose-1 visit or have left the main study (ie, completion of the main study), and the clinical database is locked and
unblinded. This analysis will include all available data up to the 12 months post-dose-1 (D365) visit. Subsequently,
participants who were originally randomized to the control arm and who have not withdrawn during the main study,
will be offered the Ebola vaccine regimen in an optional extension phase of the study.
The final analysis will be performed at study completion, defined as the date of final database lock. This will occur
after all participants have completed the last study-related visit or left the study.
SYNOPSIS
Time and Events Schedule
ABBREVIATIONS
1 INTRODUCTION
1.3.5 Overall Benefit/Risk Assessment
1.4Overall Rationale for the Study
2.1 Objectives and Endpoints
3.1 Overview of Study Design
3.2 Study Design Rationale
4PARTICIPANT POPULATION
5 INTERVENTION ALLOCATION AND BLINDING
6 DOSAGE AND ADMINISTRATION
7 INTERVENTION COMPLIANCE
8 PRESTUDY AND CONCOMITANT THERAPY
9.1.1 Overview
9.1.2 Screening Period
9.1.3 Vaccination Period
9.1.4Follow-up Period
9.3.1 Safety Assessments
9.3.2 Study Pausing Rules
9.4Immunogenicity Assessments
10.1 Completion
10.2 Discontinuation of Study Intervention/Withdrawal From the Study
11 STATISTICAL METHODS
11.6 Interim Analysis
11.7 Independent Data Monitoring Committee
11.8 Independent Medical Reviewer
12.1.1 Adverse Event Definitions and Classifications
12.3.1 All Adverse Events

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14.4Preparation, Handling, and Storage
16.1 Study-specific Design Considerations
16.2.3 Informed Consent
17.4Subject Identification, Enrollment, and Screening Logs
17.9 Monitoring
REFERENCES
Appendix 1 Test of Understanding
Rationale: Few cases of convulsions/seizures (with or without observed fever) were reported following post-
approval use of Ad26.ZEBOV in young children (1 to 17 years of age), for which a causal relation to vaccination
is plausible.
1.3.3 Known Risks
REFERENCES
Rationale:Provide information and guidance for investigators on signs and symptoms and on medical management
should very rare events of thrombosis with thrombocytopenia syndrome (TTS) occur, as observed in another Ad26-
based vaccine program (Ad26.COV2.S, COVID-19 vaccine). The Ad26.ZEBOV vaccine uses the same Ad26
vector as Ad26.COV2.S, but has different transgene inserts. To date, no cases of TTS have been reported in
Janssen’s Ad26.ZEBOV clinical studies nor in any other Ad26-based non-COVID-19 vaccine programs from
Janssen. Nonetheless, TTS will be followed in this protocol as a serious adverse event that needs to be reported to
the sponsor within 24 hours of awareness.
ABBREVIATIONS
1.3.4Potential Risks
4.2.2 Exclusion Criteria
9.1.1 Overview
12.3.2.1 Thrombosis with Thrombocytopenia Syndrome
REFERENCES
Appendix 3: Thrombotic Events to be Reported
Rationale: The time intervals that should be respected between COVID-19 vaccination and study intervention
were specified.
ABBREVIATIONS
4.3 Prohibitions and Restrictions
8 PRESTUDY AND CONCOMITANT THERAPY
Rationale: Clarified how study results may be made available to participants according to local
standards/restrictions.
16.1 Study-specific Design Considerations
Rationale: Process for protocol clarification communications added to align with Janssen internal Standard
Operation Procedures.
17.1 Protocol Clarification Communications
Rationale: A COVID-19 Appendix has been added to provide guidance to investigators for managing study-related
procedures during the COVID-19 pandemic.
18 COVID-19 Appendix: Guidance on Study Conduct During the COVID-19 Pandemic
Rationale: Minor textual changes and corrections have been made.
Throughout the protocol.

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Clinical Protocol Amendment 4VAC52150EBL2005
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Approved, Date: 28 September 2021
Amendment 3 (06 August 2020)
The overall reason for the amendment: The overall reason for the amendment is to ensure that final analysis
Clinical Study Report (CSR) is completed within 6 months of study completion, in line with European Medicines
Agency (EMA) Article 46.
The changes made to the clinical protocol VAC52150EBL2005 in order to expedite the final analysis are listed
below, including the rationale of each change and a list of all applicable sections.
Rationale: In order to expedite the final analysis, the interim analysis is being removed from the protocol. The
final analysis will be performed at study completion, now defined as final database lock, which will occur after the
last participant in the study has completed their last study-related visit, or left the study.
SYNOPSIS
3.1 Overview of Study Design
5 INTERVENTION ALLOCATION AND BLINDING
11 STATISTICAL METHODS
11.6 Interim Analysis
17.9.1 Study Completion/End of Study
Rationale: The statistical methods that will be used to analyze laboratory toxicities, vital sign abnormalities, and
physical examination findings have been updated. Laboratory abnormalities will not be summarized since
assessments are only performed at screening and pre-dose 2. A full physical examination is only conducted at
screening. At other visits, only brief, symptom-directed examinations will be performed and clinically significant
abnormal findings recorded as AEs. Therefore, separate analysis of physical examination findings will not be
performed.
SYNOPSIS
11.4Safety Analyses
Rationale: In line with the current protocol template, the Confidentiality Statement on the title page was updated
and a footer was added.
Throughout the document

VAC52150 (Ad26.ZEBOV, MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol Amendment 4VAC52150EBL2005
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
8
Approved, Date: 28 September 2021
Amendment 2 (01 October 2019)
The overall reason for the amendment: This amendment is written in response to the questions received from
FDA on 21 May 2019.
The changes made to the clinical protocol VAC52150EBL2005 are listed below, including the rationale of each
change and a list of all applicable sections.
Rationale: The current criteria for local erythema and swelling adopted in the VAC52150EBL2005 protocol are
less stringent than those used in the DMID pediatric toxicity table and ongoing Phase 2 and 3 studies in the Janssen
clinical development program. The protocol will be amended to change the criteria for local erythema and swelling
to be aligned with VAC52150EBL3001.
Local Erythema and 
Swelling
Grade 1 
Grade 2 
Grade 3 
Grade 4
VAC52150EBL2005 
(Current) 
≥10 <25 mm  
≥25 <50 mm  
≥50 mm  
Hospitalization or ER visit
for treatment
VAC52150EBL2005 
(Revised) 
<10 mm  
10 25 mm  
26 50 mm  
>50 mm or any grade 3 with
hospitalization or ER visit
for treatment
Appendix 2: Toxicity Grading Scale for Healthy Pediatric Participants up to 3 Years of Age Enrolled in
Preventive Vaccine Clinical Trials
Rationale: The pausing rules were modified to include injection site ulceration, abscess, or necrosis occurring in
2 or more participants.
9.3.2 Study Pausing Rules
Rationale: Exclusion criterion 4 was modified to reflect allergy to MenACWY. The constituents of the Nimenrix
vaccine were added to the exclusion criteria (Neisseria meningitidis polysaccharide, tetanus toxoid). The other
listed ingredients (sucrose, trometamol, sodium chloride, water for injections) are not known to be associated with
an allergic response.
4.2 Exclusion Criteria
Rationale: As axillary temperature will be measured, and this tends to underestimate the core temperature, the
upper axillary temperature limit to allow vaccination was modified from ≥38.0°C to ≥37.5°C to prevent
inadvertent vaccination of infants with low-grade fever.
1.3.5 Overall Benefit/Risk Assessment
4.2 Exclusion Criteria
6.1 Criteria for Postponement of Vaccination
Rationale: A typo in exclusion criterion 12 was corrected (platelet count <100 x 109/L instead of <100 x 1012/L).
4.2 Exclusion Criteria
Rationale: Throughout the document, it was clarified that Physical Examination findings (ie, abnormalities) prior
to Dose 1 vaccination are to be recorded as medical history and after Dose 1 as adverse event.
SYNOPSIS
Time and Events Schedule
9.3.1 Safety Assessments
11.4 Safety Analyses
Rationale: Information with regard to the number of times the parent(s)/guardians will be allowed to retake the
test of understanding (TOU) was aligned across the protocol. They will be allowed to retake the test twice and
have to achieve the passing score (≥90%) after the third time for their child to be eligible for the study.
16.1 Study-specific Design Considerations

VAC52150 (Ad26.ZEBOV, MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol Amendment 4VAC52150EBL2005
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Approved, Date: 28 September 2021
Rationale: Question 9 of the TOU was adjusted to ask the participants if the clinical staff can share information
about the participant’s baby with other people not involved in the study instead of people involved in the study.
Appendix 1: Test of Understanding
Rationale: Minor editorial changes were made throughout the document.
Throughout the document
Amendment 1 (07 Mar 2019)
The overall reason for the amendment:The overall reason for the amendment is to allow flexibility in the amount
of blood to be drawn for immunogenicity assessments and to clarify the intended study population age range.
The changes made to the clinical protocol VAC52150EBL2005 are listed below, including the rationale of each
change and a list of all applicable sections.
Rationale:Two phlebotomy methods are acceptable practice for obtaining blood from infants; however, the blood
volumes obtained for each method could be slightly different. This amendment allows the site flexibility in selecting
the most appropriate method for their population and details the differences in blood volumes according to each
method.
A total blood volume of 8.0-9.5 mL will be obtained: 2.0 mL for safety and 6.0-7.5 mL for immunogenicity
depending on the most successful phlebotomy method, either the direct (vacutainer) method or indirect (syringe)
method. If the indirect (syringe) method is chosen, the immunogenicity blood sample is 2.0 mL per visit and the
total blood volume is 8 mL. If the direct (vacutainer) method is chosen, then the immunogenicity blood sample is
2.5 mL per visit and the total blood volume is 9.5 mL. The maximum amount of blood that will be drawn on a
single visit will not exceed 3.5 mL.
SYNOPSIS
Time and Events Schedule
9.1.1 Overview
9.4 Immunogenicity Assessments
16.1 Study-specific Design Considerations
Rationale: The protocol was updated to clarify that the study population will include infants ≥4 months up to
<12 months of age.
SYNOPSIS
1.4 Overall Rationale for the Study
3.1 Overview of Study Design
3.2 Study Design Rationale
4.1 Inclusion Criteria

VAC52150 (Ad26.ZEBOV, MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol Amendment 4VAC52150EBL2005
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Approved, Date: 28 September 2021
SYNOPSIS
A Phase 2 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of a Heterologous 2-dose
Vaccination Regimen Using Ad26.ZEBOV and MVA-BN®-Filo in Infants Aged 4-11 Months in Guinea
and Sierra Leone
Janssen Vaccines & Prevention B.V. (hereafter referred to as the sponsor), in collaboration with Bavarian
Nordic GmbH (BN), and in conjunction with an Innovative Medicines Initiative (IMI) consortium led by
the sponsor and the London School of Hygiene and Tropical Medicine (LSHTM), including the Institut
National de la Santé et de la Recherche Médicale (INSERM), the University of Antwerp, and the College
of Medicine and Allied Health Sciences (COMAHS) as partners, is investigating the potential of a
prophylactic Ebola vaccine regimen (VAC52150) comprised of the following 2 candidate Ebola vaccines:
Ad26.ZEBOV is amonovalent vaccine expressing the full-length Ebolavirus (EBOV, formerly known as
Zaire ebolavirus) Mayinga glycoprotein (GP). The vaccine is produced in the human cell line PER.C6®.
MVA-mBN226B, further referred to as Modified Vaccinia Ankara (MVA)-BN®-Filo, is a multivalent
vaccine expressing the EBOV GP, the Sudan virus (SUDV) GP, the Marburg virus (MARV) Musoke GP,
and the Tai Forest virus (TAFV, formerly known as Côte d’Ivoire ebolavirus) nucleoprotein (NP). The
EBOV GP expressed by MVA-BN-Filo has 100% homology to the one expressed by Ad26.ZEBOV.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS
Main Study
Objectives 
Endpoints
Primary
 
To assess the safety and reactogenicity of a 
heterologous 2-dose vaccination  regimen 
utilizing Ad26.ZEBOV  (first vaccination; 
Dose 1) and MVA-BN-Filo (second
vaccination; 
Dose 
2) 
administered
intramuscularly  (IM) on Days 1 and 57,
respectively.
 
Solicited local and systemic adverse events
until 7 days post-dose-1 and 7 days post-
dose-2.
 
Unsolicited adverse events from the first
vaccination until 28 days post-dose-1 and from
the second vaccination  until 28 days
post-dose-2.
 
Any serious adverse events until 6 months post-
dose-2, and serious adverse events related to
study intervention until the end of the study.
Secondary
 
To assess binding antibody responses as 
measured by ELISA at 21 days post-dose-2. 
 
Binding antibody levels against the EBOV GP
using FANG ELISA (EU/mL) at 21 days post-
dose-2.
Exploratory
 
To assess binding antibody responses as 
measured by ELISA at baseline and 
12 months post-dose-1. 
 
Binding antibody levels against the EBOV GP
using FANG ELISA (EU/mL) at baseline and
12 months post-dose-1.

VAC52150 (Ad26.ZEBOV, MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol Amendment 4VAC52150EBL2005
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Approved, Date: 28 September 2021
Objectives 
Endpoints
 
To assess the neutralizing antibody response 
to the adenovirus backbone as measured by 
the Ad26 virus neutralization assay (VNA) 
at baseline.
 
Neutralizing antibody levels against the
adenovirus backbone using Ad26 VNA  at
baseline.
ELISA: enzyme-linked immunosorbent assay; EU/mL: ELISA units/mL; FANG: Filovirus Animal Nonclinical
Group.
Extension Phase
Objectives 
Endpoints
Primary
 
To 
provide 
the 
heterologous 
2-dose 
vaccination regimen (Ad26.ZEBOV on 
Day 1 and MVA-BN-Filo on Day 57) to 
participants in the control arm of the main
study.
 
Completion 
of 
the 
heterologous 
2-dose
vaccination regimen (Ad26.ZEBOV on Day 1
and MVA-BN-Filo on Day 57).
Exploratory
 
To assess the safety and reactogenicity of a 
heterologous 2-dose vaccination regimen 
utilizing Ad26.ZEBOV (first vaccination;
Dose 1) and MVA-BN-Filo (second
vaccination; 
Dose 
2) 
administered
intramuscularly (IM) on Days 1 and 57,
respectively.
 
Solicited local and systemic adverse events
until 7 days post-dose-1 and 7 days post-dose-2.
 
Unsolicited adverse events from the first
vaccination until 28 days post-dose-1 and from
the second vaccination until 28 days
post-dose-2.
 
Any serious adverse events until 28 days post-
dose-2.
Hypothesis
No formal statistical hypothesis testing is planned.
OVERVIEW OF STUDY DESIGN
Main Study
Study VAC52150EBL2005 is a Phase2, randomized, active-controlled, double-blind study to evaluate the
safety, reactogenicity, and immunogenicity of Ad26.ZEBOV (first vaccination) at a dose of5x1010 viral
particles (vp) followed by MVA-BN-Filo (second vaccination) at a dose of 1x108 infectious units (Inf U)
administered 56 days later in healthy infants aged 4-11 months (ie, 4 months up to <12 months). This
study will be conducted in Guinea and Sierra Leone.
A total number of 107 infants is targeted to be enrolled and randomized to study vaccine (Ad26.ZEBOV,
MVA-BN-Filo) or active control in a blinded fashion. Approximately equal numbers of participants will be
enrolled in each country. Within each country, there will be stratification by age group (ie,4 to ≤8 months,
and >8 to <12 months of age).
Participants in the control arm will receive the World Health Organization (WHO)-prequalified
Meningococcal Group A, C, W135, and Y conjugate vaccine MenACWY as first vaccination on Day 1 and
as second vaccination on Day 57. All study participants will be vaccinated with MenACWY at 6 months

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post-dose-2 vaccination (ie, in their second year of life), in keeping with the recommended immunization
regimen for this vaccine.
Enrollment of participants will start with vaccination of a sentinel cohort of 16 infants before exposing the
remainder of the infants to the study intervention. An Independent Data Monitoring committee (IDMC)
will be commissioned for this study.
Enrollment will be organized as follows:
- 
Eight sentinel participants will be randomized in a 1:1 ratio to receive study vaccine
(Ad26.ZEBOV, MVA-BN-Filo) or active control. The study responsible physician and
investigators will review the blinded 48-hour safety data from these 8 participants.
- 
In the absence of safety concerns, another 8 participants will be enrolled to complete the sentinel
cohort until a total of 16 participants are randomized in a 1:1 ratio to study vaccine or active control.
Study enrollment will be paused while the IDMC reviews available safety data for the first 7 days
post-dose-1 of these 16 participants.
- 
Upon a favorable review of safety data up to 7 days post-dose-1 by the IDMC, the remainder of the
participants will be randomly assigned to study vaccine or active control in a 5:2 ratio.
A similar procedure will be implemented for the second vaccination. When the last participant in the
sentinel cohort completes the 7-days post-dose-2 safety visit, the IDMC will review all available data up to
that point and will give recommendation for the continuation of the study in the remaining participants.
The blinded investigators, together with the sponsor’s medical monitor, will be responsible for the safety
monitoring of the study. If at least one pre-specified pausing rule is met, administration of study intervention
will be paused and an IDMC meeting will be convened.
After each vaccination, participants will remain under observation at the study site for at least 30 minutes
for presence of any acute reactions, or longer if deemed necessary by the investigator. Following the first
and second vaccination, any unsolicited, solicited local or systemic adverse events, and vital signs will be
documented by study-site personnel at the end ofthis observation period. In addition, solicited events will
be recorded in a diary for 7 days post-dose-1 and post-dose-2.
Unsolicited adverse events will be recorded from the first vaccination onwards until 28 days post-dose-1,
and again from the second vaccination until 28 days post-dose-2. Serious adverse events and/or special
reporting situations that are related to study procedures or related to non-investigational (concomitant)
sponsor products will be reported from the time a signed and dated informed consent form (ICF) is obtained
onwards until the end of the study. All other serious adverse events and/or special reporting situations will
be reported from the day of the first vaccination onwards until 6 months post-dose-2.
Safety assessments include solicited local or systemic adverse events, unsolicited adverse events, serious
adverse events, physical examinations (including body length and weight), vital sign measurements, and
laboratory assessments (blood samples will be collected at screening and at Day 57 pre-dose-2).
Blood samples will be collected for immunogenicity assessments at screening (ie, the baseline sample),
21 days post-dose-2, and 12 months post-dose-1.

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The study will consist of a screening period of up to 28 days, a vaccination period in which the participants
will be vaccinated at baseline (Day 1; first vaccination) followed by a second vaccination on Day 57, a
vaccination with MenACWY at 6 months post-dose-2, and a follow-up period until 12 months post-dose-1.
Extension Phase
After the last participant has completed the 12 months post-dose-1 visit or has left the main study (ie,
completion of the main study), there will be an interim database lock and unblinding of the study.
Subsequently, participants who were originally randomized to the control arm and who have not withdrawn
during the main study, will be offered the Ebola vaccine regimen in an optional extension phase of the
study. Participants opting to receive the vaccine regimen will be followed-up for safety until 28 days post-
dose-2. The IDMC will be replaced by an independent medical reviewer.
The study is considered completed at final database lock, which will occur after the last participant has
completed the last study visit or left the study.
STUDY POPULATION
The study population will consist of healthy infants, aged 4-11 months (ie, 4 months up to <12 months)
at screening for the main study(ie, blinded phase),who have received all routine immunizations appropriate
for their age, and who have normal hemoglobin, platelet and white blood cell counts at screening.
Participants who have received a candidate Ebola vaccine, or a candidate Ad26- or MVA-based vaccine in
the past, or with known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or
vaccine products, including known allergy to egg, egg products, and aminoglycosides, will be excluded.
DOSAGE AND ADMINISTRATION
Infants randomized to the Ad26.ZEBOV, MVA-BN-Filo arm will receive the following study vaccines as
a 0.5-mL IM injection into the anterolateral thigh:
- Ad26.ZEBOV: 5x1010 vp on Day 1
- MVA-BN-Filo: 1x108 Inf U on Day 57
Participants in the control arm will receive the WHO-prequalified MenACWY as first vaccination on Day 1
and as second vaccination on Day 57.
The recommended immunization series of MenACWY consists of 2 doses given 2 months apart, followed
by a booster vaccination at 12 months of age. Previously unvaccinated children may receive a single dose
in their second year of life. In keeping with the recommended immunization regimen for this vaccine, all
participants will receive a dose of MenACWY at the 6-months post-dose-2 visit. The MenACWY vaccine
will be administered as a 0.5-mL IM injection into the anterolateral thigh.
Upon completion of the main study, participants in the extension phase who were originally randomized to
the control arm will receive the same vaccine regimen as the participants in the Ad26.ZEBOV, MVA-BN-
Filo arm of the main study.
SAFETY EVALUATIONS
Brief physical examinations (including body length and weight)and vital signs will be assessed as indicated
in the Time and Events Schedule. The investigators, together with the sponsor’s medical monitor, will be
responsible for the safety monitoring of the study, and will halt vaccination of further participants in case
any of the pre-specified pausing rules have been met. An IDMC will be established to monitor data on an

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ongoing basis to ensure the continuing safety of the participants enrolled in this study. In the extension
phase, participants will be followed for safety until 28 days post-dose-2.
IMMUNOGENICITY EVALUATIONS
In the main study, blood samples (2.0-2.5 mL) for immunogenicity assessments will be collected at
screening (ie, the baseline sample), 21 days post-dose-2 and 12 months post-dose-1. During the extension
phase, no blood samples for immunogenicity evaluations will be collected.
STATISTICAL METHODS
The primary interim analysis for the blinded phase of the study will be done when all participants have
completed the 12 months post-dose-1 visit or have left the main study (ie, completion of the main study),
and the clinical database is locked and unblinded. This analysis will include all available data up to the
12 months post-dose-1 (D365) visit.
The final analysis will be performed at study completion, defined as the date of final database lock. This
will occur after all participants have completed the last study-related visit or left the study. Specific details
will be provided in the Statistical Analysis Plan.
No formal hypothesis will be tested.
Safety data will be analyzed descriptively (including 95% confidence intervals, if applicable) for
participants receiving study vaccine or active control. For each adverse event, the number and percentage
of participants who experience at least 1 occurrence of the given event will be summarized by intervention
arm. Summaries, listings, datasets, or participant narratives may be provided, as appropriate, for those
participants who die, who discontinue study intervention due to an adverse event, or who experience a
severe or a serious adverse event. Clinically significant abnormal laboratory data reported in the CRF will
be presented in the data listings. Clinically significant vital sign abnormalities and abnormal findings of
physical examinations will be recorded as AEs.
Descriptive statistics (geometric mean and 95% confidence interval, or median and range Q1-Q3, as
appropriate) will be calculated for continuous immunologic parameters at all available time points.
Graphical representations ofimmunological parameters will be made as applicable. Frequency tabulations
will be calculated for discrete (qualitative) immunologic parameters as applicable.

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i. 
Includes pulse/heart rate (at rest), respiratory rate,and body temperature.
j. 
Prior to study intervention administration and at the end of the observation period.
k. Diaries will be completed at home by either a project field worker who will visit the participant during daily visits or by the parent(s)/guardian to document
symptoms of solicited local and systemic adverse events in the evening after each vaccination and then daily for the next 7 days at approximately the same time
each day.
l. 
After the first and second vaccination, participants will remain under observation at the study site for at least 30 minutes for presence of any acute reactions, or
longer if deemed necessary by the investigator. Solicited local and systemic and unsolicited adverse events emerging during the observation period will be
recorded in the CRF.
m. Solicited adverse events will be documented in the evening after the first and second vaccination and then daily for the next 7 days, during daily home visits by
a project field worker.
n. Serious adverse events and/or special reporting situations that are related to study procedures or that are related to non-investigational (concomitant) sponsor
products will be reported from the time a signed and dated ICF is obtained onwards until the end of the study. All other serious adverse events and/or special
reporting situations will be reported from the day of the first vaccination onwards until 6 months post-dose-2.
o. Concomitant therapies must be recorded from screening onwards until 28 days post-dose-1 and from the second vaccination until 28 days post-dose-2. At the
other time points, it should only be recorded if given in conjunction with serious adverse events.
p. This will serve as the baseline sample for immunogenicity assessments.
q. A total blood volume of 8.0-9.5 mL will be obtained: 2.0 mL for safety and 6.0-7.5 mL for immunogenicity depending on the most successful phlebotomy
method, either the direct (vacutainer) method or indirect (syringe) method. If the indirect (syringe) method is chosen, the immunogenicity blood sample is 2.0 mL
per visit and the total blood volume is 8 mL. If the direct (vacutainer) method is chosen, then the immunogenicity blood sample is 2.5 mL per visit and the total
blood volume is 9.5 mL. Whenever feasible, a single phlebotomy method will be used for a given subject.

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a. Screening may be split into multiple days or visits. Retesting of values (eg, safety laboratory) that lead to exclusion is allowed once using an unscheduled visit
during the screening period, provided there is an alternative explanation for the out of range value. The safety laboratory assessments at screening are to be
performed within 28 days prior to the first vaccination (including Day 1 before vaccination) and may be repeated if they fall outside this time window. If retesting
is required, all screening procedures (except TOU) should be repeated.
b. The TOU should be administered to the parent or guardian who will provide consent, and will be administered after reading but before signing the informed
consent form (ICF).
c. Signing of the ICF for participation in the study extension needs to be done before the first study-related activity in the study extension (except TOU).
d. The investigators should ensure that all study enrollment criteria have been met at the end of the screening period and before the first vaccination on Day 1 of the
study extension. If a participant’s clinical status changes (including available laboratory results or the receipt of additional medical records) after screening but
before Day 1 of the study extension such that the participant no longer meets all eligibility criteria, then the participant will be excluded from participation in the
extension. For contraindications to receive the second vaccination in the study extension, refer to Section 6.2.
e. The brief physical examination (symptom-directed) includes also body length and weight. Physical examination findings (ie, abnormalities) after Dose 1
vaccination are to be recorded as adverse event.
f. 
Prior to study intervention administration.
g. Includes pulse/heart rate (at rest), respiratory rate, and body temperature.
h. Prior to study intervention administration and at the end of the observation period.
i. 
Diaries will be completed at home by either a project field worker who will visit the participant during daily visits or by the parent(s)/guardian to document
symptoms of solicited local and systemic adverse events in the evening after each vaccination and then daily for the next 7 days at approximately the same time
each day.
j. 
After the first and second vaccination, participants will remain under observation at the study site for at least 30 minutes for presence of any acute reactions, or
longer if deemed necessary by the investigator. Solicited local and systemic and unsolicited adverse events emerging during the observation period will be recorded
in the CRF.
k. Solicited adverse events will be documented in the evening after the first and second vaccination and then daily for the next 7 days, during daily home visits by a
project field worker.
l. 
Serious adverse events and/or special reporting situations that are related to study procedures or that are related to non-investigational (concomitant) sponsor
products will be reported from the time a signed and dated ICF is obtained onwards until the end of the study. All other serious adverse events and/or special
reporting situations will be reported from the day of the first vaccination onwards until 28 days post-dose-2. At the screening visit participants will also be asked
about serious adverse events that occurred between the D365 follow-up visit of the main phase and the start of the extension phase. These will be recorded on the
AE form.
m. Concomitant therapies must be recorded from screening onwards until 28 days post-dose-1 and from the second vaccination until 28 days post-dose-2. At the
other time points, it should only be recorded if given in conjunction with serious adverse events.

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ABBREVIATIONS
Adxx  
adenovirus serotype xx (vector)
Ad26.ZEBOV  adenovirus serotype 26 expressing the Ebola virus Mayinga glycoprotein
AE 
adverse event
BN 
Bavarian Nordic GmbH
CI 
confidence interval
COMAHS  
College of Medicine and Allied Health Sciences
CRF  
case report form
DMID  
Division of Microbiology and Infectious Diseases
EBOV  
Ebola virus
eDC  
electronic data capture
EDTA  
ethylenediaminetetraacetic acid
eDx 
extension Day x
ELISA  
enzyme-linked immunosorbent assay
EPI 
Expanded Program on Immunization
EU  
European Union
EUA  
Emergency Use Authorization
EUL 
Emergency Use Listing
EU/mL 
ELISA units per mL
EVD  
Ebola virus disease
FANG  
Filovirus Animal Nonclinical Group
GCP  
Good Clinical Practice
GMP  
Good Manufacturing Practice
GP  
glycoprotein
HITT  
heparin-induced thrombocytopenia and thrombosis
HIV  
human immunodeficiency virus
ICF  
informed consent form
ICH  
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for
Human Use (previously International Council for Harmonisation)
IDMC  
Independent Data Monitoring Committee
IEC  
Independent Ethics Committee
IM  
intramuscular(ly)
IMI 
Innovative Medicines Initiative
Inf U  
infectious units
INSERM  
Institut National de la Santé et de la Recherche Médicale
IRB  
Institutional Review Board
IWRS  
interactive web response system
kb 
kilobase
LSHTM  
London School of Hygiene and Tropical Medicine
MARV  
Marburg virus
MedDRA  
Medical Dictionary for Regulatory Activities
MVA  
Modified Vaccinia Ankara
MVA-BN-Filo Modified Vaccinia Ankara Bavarian Nordic vector expressing multiple filovirus proteins
NHP  
nonhuman primate(s)
NP  
nucleoprotein
PCR  
polymerase chain reaction
PREVAC  
Partnership for Research on Ebola Vaccination
PQC  
Product Quality Complaint
RBC  
red blood cell
RNA  
ribonucleic acid
SAP  
Statistical Analysis Plan
SUDV  
Sudan virus
SUSAR  
suspected unexpected serious adverse reaction
TAFV  
Tai Forest virus
THAM  
tris (hydroxymethyl)-amino methane
TOU  
Test of Understanding

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TTS  
thrombosis with thrombocytopenia syndrome
VISP  
vaccine induced seropositivity
vp 
viral particles
WBC  
white blood cell
WHO  
World Health Organization
DEFINITIONS OF TERMS
Study intervention  
Ad26.ZEBOV, MVA-BN-Filo, or active control (MenACWY)
Independent study 
intervention monitor 
An unblinded study intervention monitor assigned to the study who is responsible for the
unblinded interface between the sponsor and the investigational site pharmacy.
Solicited adverse 
events 
(reactogenicity) 
Local and systemic adverse events that are common and known to occur after vaccination
and that are usually collected in a standard, systematic format in vaccine clinical studies.
For the list of solicited adverse events in this study, see Section 9.3. For the purpose of
vaccine clinical studies, all other adverse events are considered unsolicited; however, this
definition should be distinguished from definitions based on pharmacovigilance guidelines.
Study Naming Convention
Clinical studies with the Ad26.ZEBOV and MVA-BN-Filo vaccines are referred to as study VAC52150EBLXXXX
(eg, study VAC52150EBL1001), but also the abbreviation EBLXXXX (eg,study EBL1001) is used in this document.

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1. 
INTRODUCTION
Janssen Vaccines & Prevention B.V. (hereafter referred to as the sponsor), in collaboration with
Bavarian Nordic GmbH (BN), and in conjunction with an Innovative Medicines Initiative (IMI)
consortium led by the sponsor and the London School of Hygiene and Tropical Medicine
(LSHTM), including the Institut National de la Santé et de la Recherche Médicale (INSERM), the
University of Antwerp, and the College of Medicine and Allied Health Sciences (COMAHS) as
partners, is investigating the potential of a prophylactic Ebola vaccine regimen (VAC52150)
comprised of the following 2 candidate Ebola vaccines:
Ad26.ZEBOV is a monovalent vaccine expressing the full-length Ebola virus (EBOV, formerly
known as Zaire ebolavirus) Mayinga glycoprotein (GP). The vaccine is produced in the human
cell line PER.C6®.
MVA-mBN226B, further referred to as Modified Vaccinia Ankara (MVA)-BN®-Filo, is a
multivalent vaccine expressing the EBOV GP, the Sudan virus (SUDV) GP, the Marburg virus
(MARV) Musoke GP, and the Tai Forest virus (TAFV, formerly known as Côte d’Ivoire
ebolavirus) nucleoprotein (NP). The EBOV GP expressed by MVA-BN-Filo has 100% homology
to the one expressed by Ad26.ZEBOV.
The monovalent vaccine is part of an ongoing development program for a multivalent vaccine
against multiple filoviruses that cause disease in humans, including EBOV, SUDV, and MARV.
For the most up-to-date nonclinical and clinical information regarding Ad26.ZEBOV and
MVA-BN-Filo, refer to the latest versions of the Investigator’s Brochures and Addenda (if
applicable).12,13,14,15,16 A brief summary of the nonclinical and clinical information available at the
time of the protocol writing is provided below.
The term “study intervention” throughout the protocol, refers to study vaccine (Ad26.ZEBOV,
MVA-BN-Filo)/active control.
The term "sponsor" used throughout this document refers to the entities listed in the Contact
Information page(s), which will be provided as a separate document.
The term “study” refers to the main double blinded part of the study. The current protocol describes
the main study unless clearly specified otherwise.
1.1. 
Background
Ebola viruses belong to the Filoviridae family and cause Ebola virus disease (EVD), which can
induce severe hemorrhagic fever inhumans andnonhumanprimates (NHP). Case fatality rates in
EVD  range from 25% to 90% (average: 50%), according to the World Health Organization
(WHO).22 These viruses are highly prioritized by the United States Government, who has defined
them as ‘Category A’ agents, due to the high mortality rate of infected individuals. At the time of
protocol writing, no licensed vaccine, treatment or cure existed for this disease.
Filoviruses are named for their long, filamentous shape. Within this filamentous virus, a single
19-kilobase (kb) negative-sense ribonucleic acid (RNA) genome encodes 7 proteins: the GP, the

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polymerase, the NP, the secondary matrix protein, the transcriptional activator, the polymerase
cofactor, and the matrix protein. The virion surface is covered by homotrimers of the viral GP,
which is believed to be the sole host attachment factor for filoviruses. Following cell entry, the
viruses replicate their genomes and viral proteins in the cytoplasm using an RNA-dependent RNA
polymerase, which is carried into the cell together with the virus.10
In this Phase 2 study, the sponsor’s adenovirus serotype 26 (Ad26) vector expressing the EBOV
Mayinga GP (Ad26.ZEBOV) and the MVA-BN vector with EBOV, SUDV, and MARV GP
inserts and TAFV NP insert (MVA-BN-Filo) will be evaluated as a heterologous 2-dose regimen,
in which one vaccine (Ad26.ZEBOV) is used to prime a filovirus-specific immune response and
the other vaccine (MVA-BN-Filo) is used to boost the immune response 56 days later. The EBOV
GP that circulated in West Africaduring the 2013-2016 epidemic had 97% homology to the EBOV
GP used in this vaccine regimen.3
Clinical studies
The safety, reactogenicity,and immunogenicity of the Ad26.ZEBOV and MVA-BN-Filo vaccines
are being evaluated in a number of completed and ongoing clinical studies in adults and children
≥1 year of age. The sponsor’s current clinical development plan contains 4 completed Phase 1
studies (EBL1001, EBL1002, EBL1003, EBL1004), the ongoing Phase 1 studies EBL1005 and
EBL1007, 4 ongoing Phase 2 studies (EBL2001, EBL2002, EBL2003, and EBL2004/Partnership
for Research on Ebola Vaccination [PREVAC]), and 5 ongoing/planned Phase 3 studies
(EBL3001, EBL3002, EBL3003, EBL3004, and EBL4001). Monovalent Ad26.ZEBOV vaccine
and multivalent MVA-BN-Filo vaccine are combined in homologous or heterologous 2-dose
regimens in which each vector is used to prime a filovirus-specific immune response followed by
a second immunization with the same or the other vector at 7-, 14-, 28-, 56-, or 84-day intervals.
An additional Phase 1 study with the multivalent vaccine VAC69120FLV1001 has been
completed, where a group receiving Ad26.ZEBOV, MVA-BN-Filo in a 56-day interval was
included as a control arm.
As of 19 October 2018 (ie, at the time of protocol writing), an estimated 6,500 participants (adults,
children, HIV+ adults; estimation based on randomization ratios) have received at least the first
vaccination (Ad26.ZEBOV, MVA-BN-Filo, or placebo/active comparator). Of these,
approximately 1,600 children (1-17 years of age) and 400 HIV+ adults have been vaccinated.
Refer to the latest versions of the Ad26.ZEBOV and MVA-BN-Filo Investigator’s Brochures and
Addenda (if applicable) for more details.12,13,14,15,16 A summary is provided below.
Phase 1 studies
Final analysis data are available for the 4randomized, placebo-controlled, observer-blind, Phase 1
studies that were conducted in healthy adult Western (United Kingdom and United States) and
African (Kenya, Tanzania, and Uganda) male and female participants, aged ≥18 to ≤50 years,
outside of EBOV outbreak areas. In  these studies, Ad26.ZEBOV and MVA-BN-Filo were
administered intramuscularly (IM)as homologousor heterologous 2-dose regimens, in 7-, 14-, 28-,
or 56-day intervals.

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Both vaccines are well tolerated, with no safety concerns identified. Reactogenicity was slightly
more commonly reported among participants following Ad26.ZEBOV than following MVA-BN-
Filo vaccination. The most frequently reported solicited adverse events reported in the 4individual
Phase 1 studies were injection site pain, injection site warmth, fatigue, headache, and myalgia. The
most frequently reported unsolicited adverse events were hypokalemia, neutropenia, and
neutrophil count decreased.
The Ad26.ZEBOV, MVA-BN-Filo vaccine regimens are highly immunogenic and induce
considerable humoral as well as cellular immune responses, regardless of vaccine sequence and
dose level.
Phase 2/3 Studies
In the ongoing Phase 2 and 3 studies, enrollment of both adults and children is complete. Safety
data from studies EBL2001 (United Kingdom, France), EBL2002 (Kenya, Uganda, Burkina Faso,
Côte D’Ivoire), EBL3001 (Sierra Leone), EBL3002 (United States), and EBL3003 (United States)
have been partially unblinded to group level in all participants in the Phase 2 and 3 studies for
whom clean data up to the 6-months post-dose-2 visit are available. For participants who either
have not completed the 6-months post-dose-2 visit or whose data are not considered clean, blinded
group safety data is described below. The serious adverse event databases have been reconciled
and include, in addition to the studies listed below, serious adverse event data from EBL2004
(PREVAC).
In general, the vaccination regimen of Ad26.ZEBOV followed by MVA-BN-Filo 56 days later
was well tolerated and no safety signals were identified. The majority of solicited adverse events
were of mild or moderate intensity after vaccination with Ad26.ZEBOV or MVA-BN-Filo. The
frequency of grade 3 pyrexia (≥39.0°C) was less than 1% following vaccination and the incidence
of any febrile response was less than 7.0% in any group. As expected, the frequency of local and
systemic reactogenicity was more common in healthy adult participants who received active
vaccine compared to placebo and was similar to the incidence reported in the Phase 1 studies.
Reactogenicity was also slightly more commonly reported among participants following
Ad26.ZEBOV than following MVA-BN-Filo vaccination which was also noted in the Phase 1
studies.
A review of the unblinded safety summary reveals that serious adverse events were reported in
46 healthy adults (2.2%) vaccinated with the active vaccine regimen and in 9 participants (2.2%)
vaccinated with placebo. There was only one serious adverse event reported in HIV+ adults which
occurred in the active vaccine group. From the still blinded studies, a total of 35 serious adverse
events have been reported in adults, adolescents and children in study EBL2004 (PREVAC) of
which approximately 23 may have been randomized to active vaccine based on the randomization
schedule. One suspected unexpected serious adverse reaction (SUSAR) of small fiber neuropathy
was reported following administration of Ad26.ZEBOV and 1 SUSAR of generalized pruritus was
reported following administration of MVA-BN-Filo. There are no adverse drug reactions or events
of special concern listed in the Investigator’s Brochures.

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Safety data in pediatric participants
Data on pediatric participants aged 1-3, 4-11, and 12-17 years from studies EBL2002 and
EBL3001 are provided in a blinded manner (Table 1).
Table 1: 
Frequency of Solicited and Unsolicited Adverse Events in Children and Adolescents From
Studies EBL2002 and EBL3001 –Blinded Data
Adolescents 
(12-17 years of age) 
Children 
(4-11 years of age) 
Young children
(1-3 years of age)
N=323a) 
N=324a) 
N=192b)
n 
% 
n 
% 
n 
%
Any solicited AEs 
189 
58.5 
197 
60.8 
85 
44.3
Any solicited grade 3 AEs 
7 
2.2 
3 
0.9 
3 
1.6
Any solicited local AEs 
115 
35.6 
129 
39.8 
31 
16.1
Any solicited local grade 3 AEs 
2 
0.6 
3 
0.9 
0 
0.0
Any solicited systemic AEs 
164 
50.8  
139 
42.9 
68 
35.4
Any solicited systemic grade 3 
AEs 
5 
1.5 
1 
0.3
3
1.6
Injection site pain  
105 
32.5 
114 
35.2 
30 
15.6
Headache 
127 
39.3 
65c) 
33.9 
- 
-
Fatigue 
83 
25.7 
31c) 
16.1 
- 
-
Any pyrexia (defined as ≥38°C) 
16 
5.0 
41 
12.7 
35 
18.2
Grade 3 pyrexia (defined as
≥39°C)
4 
1.2 
0 
0.0 
2 
1.0
Any unsolicited AEs 
190 
58.8 
187 
57.7 
156 
81.3
Any unsolicited grade 3 AEs 
33 
10.2 
3 
0.9 
14 
7.3
Serious adverse events 
2 
0.6 
7 
2.2 
10 
5.2
Serious adverse events within
28 days post any vaccination  
0 
0.0 
0 
0.0 
8 
4.2
AE: adverse event
Note: Data are from ongoing studies EBL2002 and EBL3001 with a snapshot data cut-off date of 25 September
2018 (EBL2002) and 19 September 2018 (EBL3001). These are data that were available at the time of
protocol writing.
a) Based on studies EBL2002 and EBL3001.
b) Based on study EBL3001.
c) This was not a solicited AE in the 4 to 11-year-olds in EBL2002. Therefore, the denominator is based solely on
EBL3001 (N=192).
The majority of the pediatric participants experienced at least 1 solicited adverse event post-
vaccination (regimen). Approximately a third of the pediatric participants experienced at least
1 solicited local adverse event post-vaccination, with 5 participants reporting at least 1 grade 3
event. The most frequent solicited local adverse event was injection site pain. Solicited systemic
adverse events were also common in any age group, with 9 participants reporting at least 1 grade 3
event. Headache and fatigue were the most frequent systemic adverse events among adolescents.
Irritability/fussiness/crying/screaming, reduced activity/somnolence/fatigue and loss of appetite
were common among children (4-11 years). Pyrexia (defined as ≥38°C) was reported in 5.0% of
the adolescents, 12.7% of the children (4-11 years) and 18.2% of the young children (1-3 years).
Four adolescents and 2 young children (1-3 years) reported a grade 3 pyrexia (defined as ≥39°C).
Unsolicited adverse events were reported in the majority of adolescents and children with
approximately equal incidence. Thirty-three adolescents and 3 children reported at least 1 grade 3

VAC52150 (Ad26.ZEBOV, MVA-BN-Filo [MVA-mBN226B])
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unsolicited adverse event. Infections/infestations were the most frequently reported classes of
unsolicited adverse events.
There was 1 serious adverse event in Cohort 2b of study EBL2002: a 12-year-old male participant
developed fever from malaria on Day 80 (post-dose-2 follow-up phase) and died 3 days later. This
event was considered not related to the study vaccination.
In the Phase 3 study EBL3001, 192 children aged 1-3 years were randomized to receive the active
vaccine or placebo. The blinded data available at the time of protocol writing, have revealed no
major safety concerns thus far.
1.2. 
Active Comparator Vaccine
MenACWY
Participants in the control arm will receive the WHO-prequalified Meningococcal Group A, C,
W135, and Y conjugate vaccine MenACWY as first vaccination  on Day 1 and as second
vaccination on Day 57. All study participants will be vaccinated with MenACWY at 6 months
post-dose-2 (ie, in their second year of life), in keeping with the recommended immunization
regimen for this vaccine.
1.3. 
Benefit/Risk Section
1.3.1. 
Known Benefits
Ad26.ZEBOV and MVA-BN-Filo
The clinical benefit of 2-dose combinations of Ad26.ZEBOV  and MVA-BN-Filo is to be
established.
MenACWY
To offer clinical benefit to participants in the control arm, an active vaccine MenACWY was
chosen instead of placebo. Even when meningitis is diagnosed early and adequate treatment is
started, 5% to 10% of patients die, typically within 24to 48 hours after the onset of symptoms.
Left untreated, up to 50% of cases may die. Bacterial meningitis may also result in brain damage,
hearing loss or a learning disability in 10% to 20% of survivors.23,24
MenACWY is a WHO-prequalified vaccine indicated for active immunization of persons at risk
of exposure to Neisseria meningitidis serogroups A, C, W135 and Y, to prevent invasive disease.
1.3.2. 
Potential Benefits
Ad26.ZEBOV and MVA-BN-Filo
Participants may benefit from clinical testing and physical examination; others may benefit from
the knowledge that they may aid in the development of an Ebola vaccine. There is no direct
individual benefit from vaccination for the participants at the current development stage.

VAC52150 (Ad26.ZEBOV, MVA-BN-Filo [MVA-mBN226B])
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1.3.3. 
Known Risks
Ad26.ZEBOV and MVA-BN-Filo
The safety, reactogenicity,and immunogenicity of the Ad26.ZEBOV and MVA-BN-Filo vaccines
are being evaluated in a number of completed and ongoing clinical studies in adults and children
≥1 year of age. In these clinical studies, both vaccines are well tolerated, with no safety concerns
identified. The vaccines mainly elicited some solicited local and systemic reactions, as expected
with injectable vaccines, and no serious safety concerns in study participants. At the time of
protocol writing, MVA-BN-based vaccines have been administered to more than 8,100 individuals
without unexpected or serious adverse reactions reported. For details, see the safety data presented
in Section 1.1.
Based on data from post-approval use in pediatrics (1 to 17 years of age) febrile seizure was
identified as a rare adverse reaction in this population. Few cases of convulsions/seizures (with or
without observed fever) were reported following post-approval use of Ad26.ZEBOV in young
children, for which a causal relation to vaccination is plausible.15
In general, febrile seizures are prevalent, occurring in up to 5% of children, with the overall
incidence estimated to be 460/100,000 in the age group of 0 4 years with peak incidence in the
second year of life.17 There may be developmental reasons for this observation since about 98-99%
of children who experience febrile seizures recover without any sequelae or recurrence. Because
the occurrence of febrile seizures (even without vaccination) is fairly common, the Brighton
Collaboration has stressed that generalized convulsive seizure that follows administration of a
vaccine may be temporally associated with, but is not necessarily the result of, administration of a
vaccine.4
MenACWY
Very common side effects (affecting ≥1 in 10 people) of MenACWY vaccination include pain,
erythema and swelling at the injection site, headache, feeling tired, irritable or sleepy, feeling
generally unwell, and loss of appetite. For further information on the side effects of the
administered vaccine by patient age group, refer to the most recent versions of the applicable
vaccine prescribing information.
1.3.4. 
Potential Risks
The following potential risks will be monitored during the study and are specified in the protocol:
Risks Related to Vaccination
In general, IM injection may cause local itching, warmth, pain, tenderness, erythema, swelling,
arm discomfort or bruising of the skin at vaccine injection sites.
Participants may exhibit general signs and symptoms associated with administration of a vaccine,
including fever, chills, rash, nausea/vomiting, general itching, loss of appetite, diarrhea, decreased
activity/lethargy, irritability/crying. These side effects will be monitored, but are generally short-
term and do not require treatment.

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Participants may have an allergic reaction to the vaccination. An allergic reaction may cause a
rash, hives or even anaphylaxis. Severe reactions are rare. Medications must be available in the
clinic to treat serious allergic reactions.
Risks from Blood Draws
As with all clinical studies requiring blood sampling, there are risks associated with venipuncture
and multiple blood sample collection. Blood drawing may cause pain, tenderness, bruising,
bleeding, dizziness, vaso-vagal response, syncope, and, rarely, infection at the site where the blood
is taken. The total blood volume to be collected is considered to be an acceptable amount of blood
over this time period from the population in this study (see Section 16.1).
Concomitant Vaccination
Concomitant vaccination might have an influence on both safety profile and immunogenicity of
Ad26.ZEBOV and MVA-BN-Filo. Likewise, the study intervention might have an influence on
both safety profile and immunogenicity of any concomitant vaccination. Therefore, a participant
should not receive a live-attenuated vaccine from 30 days before the first vaccination until 30 days
after the second vaccination unless a vaccine preventable disease such as measles emerges which
would warrant administration of live-attenuated vaccines. Immunizations with inactivated
vaccines should be administered at least 15 days before or after administration of any study
intervention in order to avoid any potential interference in efficacy of the routine immunizations
or the interpretation of immune responses to study intervention, as well as to avoid potential
confusion with regard to attribution of adverse reactions. However, if a vaccine is indicated in a
post-exposure setting (eg, rabies or tetanus), it must take priority over the study intervention.
Otherwise, a participantwill not postpone, forego or delay the receipt of any recommended vaccine
according to local schedules (eg, Expanded Program on Immunization [EPI] schedule according
to the WHO regional office for West Africa).
Note: National Immunization Plans will be available on site and these will be taken into
consideration when planning vaccination schedules. Vaccination cards will be checked before
administration of study intervention.
Vaccine Induced Seropositivity
The potential of a participant becoming PCR-positive after vaccination was assessed in study
EBL1002. The risk for false positives is low and expected to decrease rapidly over time after
administration ofAd26.ZEBOV, MVA-BN-Filo.
In general, uninfected participants in Ebola vaccine studies may develop Ebola-specific antibodies
as a result of an immune response to the candidate Ebola vaccine, referred to as vaccine induced
seropositivity (VISP). These antibodies may be detected in Ebola serologic tests, causing the test
to appear positive even in the absence of actual Ebola infection. VISP may become evident during
the study, or after the study has been completed.

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Unknown Risks
There may be other risks that are not known. If any significant new risks are identified, the
principal investigator and participants (parents/guardian) will be informed.
Thrombosis in combination with thrombocytopenia (thrombosis with thrombocytopenia syndrome
[TTS]), has been observed following vaccination with the Janssen COVID-19 (Ad26.COV2.S)
vaccine. As of 31 August 2021, there have been 2 to 3.1 cases reported per 1 Million adults who
were vaccinated with the Janssen COVID-19 vaccine. Reports include severe cases of venous
thrombosis at unusual sites such as cerebral venous sinus thrombosis (CVST), splanchnic vein
thrombosis and arterial thrombosis, in combination with thrombocytopenia. The associated
symptoms began typically within 4weeks after vaccination  or sometimes later. These events
occurred mostly in women under 60 years of age, but have also been observed in men and in
individuals older than 60 years of age. Cases of thrombosis in combination with thrombocytopenia
have been fatal in some cases. The exact pathophysiology of TTS is unclear. This event has not
been observed to date with any other Janssen Ad26-based vaccines (including with
Ad26.ZEBOV), although TTS has been reported following vaccination with another COVID-19
vaccine based on modified adenovirus (the Astra-Zeneca COVID vaccine). Participants should be
instructed to seek immediate medical attention if they develop symptoms such as shortness of
breath, chest pain, leg pain or swelling, persistent abdominal pain, severe or persistent headaches,
blurred vision or other vision changes, mental status changes or seizures (fits), skin bruising or
petechiae beyond the site of vaccination or easy bleeding.
1.3.5. 
Overall Benefit/Risk Assessment
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:
 To date, safety data from the studies in the clinical development program revealed no
significant safety issues (see Section 1.1). Further experience from Ad26.ZEBOV or MVA-
BN-Filo will be gained from currently ongoing clinical studies.
 For all participants, there are pre-specified pausing rules that would result in pausing of further
vaccination if predefined conditions occur, preventing exposure of new participants to study
intervention  until an Independent Data Monitoring Committee (IDMC  - main study) or an
independent medical reviewer (extension phase) reviews all safety data (seeSections 3.1, 9.3.2
and11.7).
 Only participants who meet all inclusion criteria and none of the exclusion criteria (specified
in Section 4) will be allowed to participate in this study (main study and extension phase). The
selection criteria include adequate provisions to minimize the risk and protect the well-being
of participants in the study.
 Several safety measures are included in this protocol to minimize the potential risk to
participants, including the following:
- Vaccination in the main study will start with a sentinel cohort of 16 participants before
exposing the remainder of the infants to the study intervention. See details in Section 3.1.

VAC52150 (Ad26.ZEBOV, MVA-BN-Filo [MVA-mBN226B])
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- Participants will remain at the site for at least 30 minutes after each vaccination to monitor
the development of any acute reactions, or longer if deemed necessary by the investigator
(eg, in case of grade 3 adverse events). Refer to Section 6 for more information on
emergency care.
- Safety evaluations (physical examinations and vital sign measurements) will be performed
at scheduled visits during the study, as indicated in the Time and Events Schedule.
- The investigator or clinical designee will document unsolicited adverse events from the
first vaccination (Day 1) onwards until 28 days post-dose-1, and again from the second
vaccination (Day 57) onwards until 28 days post-dose-2. The investigator or clinical
designee will document serious adverse events and/or special reporting situations that are
related to study procedures or that are related to non-investigational (concomitant) sponsor
products from the time a signed and dated informed consent form (ICF) is obtained
onwards until the end of the study. All other serious adverse events and/or special reporting
situations will be reported from the day of the first vaccination onwards until 6 months
post-dose-2 for the main study, and until 28 days post-dose-2 for the extension phase.
- Any clinically significant abnormalities (including those persisting at the end of the
study/early withdrawal) will be followed by the investigator until resolution or until a
clinically stable endpoint is reached.
- Participants will discontinue study intervention for the reasons included in Section 10.2.
- If acute illness (excluding minor illnesses such as diarrhea or mild upper respiratory tract
infection) or axillary temperature ≥37.5°C occur at the scheduled time for vaccination, the
participant may be vaccinated up to 10 days beyond the window allowed for the scheduled
vaccination, or be withdrawn from that vaccination at the discretion of the investigator and
after consultation with the sponsor (see Section 6.1).
- Contraindications to the second vaccination and MenACWY vaccination at 6 months post-
dose-2 are included in Section 6.2.
1.4. 
Overall Rationale for the Study
This Phase 2 study aims to improve preparedness for future Ebola outbreaks by vaccination of a
new, at-risk population. This study will be conducted in healthy infants aged 4-11 months (ie,
4months up to <12 months) (referred to as ‘infants’) in Guinea and Sierra Leone. This study will
expand the safety, reactogenicity, and immunogenicity database for VAC52150 to infants
vaccinated with a heterologous 2-dose regimen with Ad26.ZEBOV followed by MVA-BN-Filo
administered 56 days later.
This study will build on earlier studies with the candidate Ebola vaccines in older children aged
1 to 17 years (EBL2002: 4-11 and 12-17 years; EBL3001: 1-3, 4-11, and 12-17 years). Though
the incidence of EVD in younger children is low, it has been reported that the mean incubation
period (the average time from infection until symptom onset) in children was shortest on average
in the youngest children, with means ranging from 6.9 days (95% confidence interval [CI], 5.1-9.5)
in 14 children younger than 1 year of age, to 9.8 days (95% CI, 8.7-11.1) in 184 children

VAC52150 (Ad26.ZEBOV, MVA-BN-Filo [MVA-mBN226B])
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10-15 years of age. Younger children also had shorter times from symptom onset to hospitalization
and from symptom onset to death, and the highest mortality rate.1,20 It is therefore important to
evaluate any vaccine for Ebola for safety and immunogenicity in this population.
A study extension phase has been instituted to provide control arm participants who were enrolled
in the main study the opportunity to receive the Ebola vaccine regimen.
2. 
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS
2.1. 
Objectives and Endpoints
Main Study
Objectives 
Endpoints
Primary
 
To assess the safety and reactogenicity of a
heterologous 
2-dose 
regimen 
utilizing
Ad26.ZEBOV (first vaccination; Dose 1) and
MVA-BN-Filo (second vaccination; Dose 2)
administered IM  on Days 1 and 57,
respectively.
 
Solicited local and systemic adverse events
until 7 days post-dose-1 and 7 days post-
dose-2.
 
Unsolicited adverse events from the first
vaccination until 28 days post-dose-1 and
from the second vaccination until 28 days
post-dose-2.
 
Any serious adverse events until 6 months
post-dose-2, and serious adverse events
related to study intervention until end of the
study.
Secondary
 
To assess binding antibody responses as
measured by ELISA at 21 days post-dose-2.
 
Binding antibody levels against the EBOV
GP using FANG ELISA (EU/mL) at 21 days
post-dose-2.
Exploratory
 
To assess binding antibody responses as
measured by ELISA at baseline and 12 months
post-dose-1.
 
Binding antibody levels against the EBOV
GP using FANG ELISA (EU/mL) at
baseline and 12 months post-dose-1.
 
To assess the neutralizing antibody response to
the adenovirus backbone as measured by Ad26
virus neutralization assay (VNA) at baseline.
 
Neutralizing antibody levels against the
adenovirus backbone using Ad26 VNA at
baseline.
ELISA: enzyme-linked immunosorbent assay, EU/mL: ELISA units/mL; FANG: Filovirus Animal Nonclinical
Group.
Extension Phase
Objectives 
Endpoints
Primary
 
To provide the heterologous 2-dose vaccination 
regimen (Ad26.ZEBOV on Day 1 and MVA- 
BN-Filo on Day 57) to participants in the control 
arm of the main study.
 
Completion of the heterologous 2-dose
vaccination regimen (Ad26.ZEBOV on
Day 1 and MVA-BN-Filo on Day 57).

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Approved, Date: 28 September 2021
Objectives 
Endpoints
Exploratory
 
To assess the safety and reactogenicity of a 
heterologous 2-dose vaccination regimen 
utilizing Ad26.ZEBOV (first vaccination; 
Dose 1) 
and 
MVA-BN-Filo 
(second
vaccination; 
Dose 
2) 
administered
intramuscularly (IM) on Days 1 and 57,
respectively.
 
Solicited local and systemic adverse events
until 7 days post-dose-1 and 7 days
post-dose-2.
 
Unsolicited adverse events from the first
vaccination until 28 days post-dose-1 and
from the second vaccination until 28 days
post-dose-2.
 
Any serious adverse events until 28 days
post-dose-2.
Refer to Section 9 for evaluations related to endpoints.
2.2. 
Hypothesis
No formal statistical hypothesis testing is planned.
3. 
STUDY DESIGN AND RATIONALE
3.1. 
Overview of Study Design
3.1.1. 
Main Study
This is a Phase 2, randomized, active-controlled, double-blind study to evaluate the safety,
reactogenicity, and immunogenicity of Ad26.ZEBOV (first vaccination) at a dose of5x1010 viral
particles (vp) followed by MVA-BN-Filo (second vaccination) at a dose of 1x108 infectious units
(Inf U) administered 56 days later in healthy infants aged 4-11 months (ie, 4 months up to
<12 months). This study will be conducted in Guinea and Sierra Leone.
A total number of 107 infants is targeted to be enrolled and randomized to study vaccine
(Ad26.ZEBOV, MVA-BN-Filo) or active control in a blinded fashion. Approximately equal
numbers of participants will be enrolled in each country. Within each country, there will be
stratification by age group (ie,4 to ≤8 months, and >8 to <12 months of age).
Participants in the control arm will receive the WHO-prequalified Meningococcal Group A, C,
W135, and Y conjugate vaccine MenACWY as first vaccination  on Day 1 and as second
vaccination on Day 57. All study participants will be vaccinated with MenACWY at 6 months
post-dose-2 (ie, in their second year of life), in keeping with the recommended immunization
regimen for this vaccine.
Enrollment of participants will start with vaccination of a sentinel cohort of 16 infants before
exposing the remainder of the infants to the study intervention. An IDMC will be commissioned
for this study. Refer to Section 11.7 for details.

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Enrollment will be organized as follows:
- Eight sentinel participants will be randomized in a 1:1 ratio to receive study vaccine
(Ad26.ZEBOV, MVA-BN-Filo) or active control. The study responsible physician and
investigators will review the blinded 48-hour safety data from these 8 participants.
- In the absence of safety concerns, another 8 participants will be enrolled to complete the
sentinel cohort until a total of 16 participants are randomized in a 1:1 ratio to study vaccine
or active control. Study enrollment will be paused while the IDMC reviews available safety
data for the first 7 days post-dose-1 of these 16 participants.
- Upon a favorable review of safety data up to 7 days post-dose-1 by the IDMC, the
remainder of the participants will be randomly assigned to study vaccine or active control
in a 5:2 ratio.
A similar procedure will be implemented for the second vaccination (see Figure 1). When the last
participant in the sentinel cohort completes the 7-days post-dose-2 safety visit, the IDMC will
review all available data up to that point and will give recommendation for the continuation of the
study in the remaining participants.

VAC52150 (Ad26.ZEBOV, MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol Amendment 4VAC52150EBL2005
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Approved, Date: 28 September 2021
Figure 1: 
Schematic Overview of the Main Study
Sentinel participants
Dose 1 
(Day 1) 
n=8
(1:1 study vaccine: active control)
48 hours 
post-dose-1
IDMC
Remainder of participants
n=8
(1:1 study vaccine: active control)
7 days
post-
dose-1
n=91
(5:2 study vaccine: active control)
Sentinel participants
Dose 2
(Day 57)
n=8
(1:1 study vaccine: active control)
48 hours
post-dose-2
IDMC  
Remainder of participants
n=8
(1:1 study vaccine: active control)
7 days
post-
dose-2
n=91
(5:2 study vaccine: active control)
Study vaccine: Ad26.ZEBOV, MVA-BN-Filo; active control: MenACWY.
: review of available safety data
: IDMC review of available safety data
The blinded investigators, together with the sponsor’s medical monitor,will be responsible for the
safety monitoring of the study. If at least one pre-specified pausing rule is met, administration of
study intervention will be paused and an IDMC meeting will be convened (see Section 9.3.2).
After each vaccination, participants will remain under observation at the study site for at least
30 minutes for presence of any acute reactions, or longer if deemed necessary by the investigator.
Following the first and second vaccination, any unsolicited, solicited local or systemic adverse
events, and vital signs will be documented by study-site personnel at the end of this observation
period.
The participant’s parent/guardian will be given a thermometer, ruler and participant diary with
instructions for the proper recording of events occurring after the first and second vaccination.
Diaries will be completed at home by either a project field worker who will visit the participant or
by the parent(s)/guardian to document solicited local (at injection site) and systemic adverse events
and body temperature, beginning on the evening of the first and second vaccination, and then daily
for the next 7 days. Temperatures should be taken at approximately the same time each day,
preferably in the evening and additionally whenever the child feels warm. Study-site personnel
will collect and review participant diary information at the 7-day post-vaccination visit (first and
second vaccination).

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Unsolicited adverse events will be recorded from the first vaccination (Day 1) onwards until
28 days post-dose-1, and again from the first vaccination (Day 57) onwards until 28 days post-
dose-2. Serious adverse events and/or special reporting situations that are related to study
procedures or are related to non-investigational (concomitant) sponsor products will be reported
from the time a signed and dated ICF is obtained onwards until the end of the study. All other
serious adverse events and/or special reporting situations will be reported from the day of the first
vaccination onwards until 6 months post-dose-2.
Safety assessments include solicited local or systemic adverse events, unsolicited adverse events,
serious adverse events, physical examinations (including body length and weight), vital sign
measurements, and laboratory assessments (blood samples will be collected at screening and at
Day 57 pre-dose-2).
Blood samples will be collected for immunogenicity assessments at screening (ie, the baseline
sample), 21 days post-dose-2, and 12 months post-dose-1.
The study will consist of a screening period of up to 28 days, a vaccination period in which the
participants will be vaccinated at baseline (Day 1; first vaccination) followed by a second
vaccination on Day 57, a vaccination with MenACWY at 6 months post-dose-2, and a post-dose-2
follow-up until 12 months post-dose-1.
The main study is considered completed after the last participant has completed the 12 months
post-dose-1 visit or has left the main study and the study has been unblinded.
3.1.2. 
Extension Phase
After the last participant has completed the 12 months post-dose-1 visit or has left the main study
(ie, completion of the main study), there will be an interim database lock and unblinding of the
study. Subsequently, participants who were originally randomized to the control arm and who have
not withdrawn during the main study, will be offered the Ebola vaccine regimen in an optional
extension phase of the study. Participants opting to receive the vaccine regimen will be followed-
up for safety until 28 days post-dose-2. The IDMC will be replaced by an independent medical
reviewer. No immunogenicity assessments will be performed in the extension phase.
3.2. 
Study Design Rationale
This study is designed to obtain information on the safety, reactogenicity and immunogenicity in
infants aged 4-11 months (ie, 4 months up to <12 months), in order to be prepared for a future
Ebola outbreak. Infants younger than 4 months of age are not included to avoid interference with
routine immunization schedules.
The measures taken in this study ensure the safety of this population. A full blood count will be
performed at screening because there is a high prevalence of anemia in this population. In the
Phase 3 study EBL3001, 192 children aged 1-3 years old were randomized to receive the active
vaccine or placebo. The blinded data available at the time of protocol writing, have revealed no
major safety concerns thus far.

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Blinding and Control
An active control will be used to establish the frequency and magnitude of changes in clinical
endpoints that may occur in the absence of active intervention. Randomization will be used to
minimize bias in the assignment of participants to intervention arms, to increase the likelihood that
known and unknown participant attributes (eg, demographic and baseline characteristics) are
evenly balanced across intervention arms, and to enhance the validity of statistical comparisons
across intervention arms. Blinded intervention will be used to reduce potential bias during data
collection and evaluation of clinical endpoints.
The extension phase for participants enrolled in the control arm will be open label.
4. 
PARTICIPANT POPULATION
4.1. 
Main Study
Screening for eligible participants will be performed within 28 days before administration of the
study intervention.
The inclusion and exclusion criteria for enrolling participants in this study are described in the
following 2 subsections. If there is a question about the inclusion or exclusion criteria below, the
investigator must consult with the appropriate sponsor representative and resolve any issues before
enrolling a participant in the study. Waivers are not allowed.
4.1.1. 
Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1. 
Parent(s) (preferably both if available or as per local requirements)/guardian must sign an
ICF indicating that he or she understands the purpose of, and procedures required for the
study, and potential risks and benefits ofthe study, and are willing to allow their child to
participate in the study.
2. 
Parent(s)/guardian are willing/able to ensure that their child adheres to the prohibitions
and restrictions specified in this protocol (see Section 4.3).
3. 
The parent(s)/guardian must be at or above the age of legal consent in the jurisdiction in
which the study is taking place.
4. 
Infant must be aged between 4and 11 months (ie, 4 months up to <12 months) on the
day of randomization.
5. 
Infant must be healthy in the investigator’s clinical judgment (and the parent(s)/guardian)
on the basis of medical history, physical examination, vital signs and clinical laboratory
tests performed at screening.

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Note: The safety laboratory assessments at screening are to be performed within 28 days
prior to the first vaccination on Day 1 (including Day 1 before vaccination) and may be
repeated if they fall outside this time window.
Note: If laboratory screening tests are out of range and deemed clinically significant,
repeating screening tests to assess eligibility is permitted once during the screening
period, using an unscheduled visit.
6. 
Infant has received all routine immunizations appropriate for his or her age at the time of
enrollment as documented in the vaccination cards presented by the parent(s)/guardian.
Participants are allowed to catch up on routine immunizations if needed (support for
beneficial vaccines may be offered to participants).
7. 
Parent(s)/guardian is available and willing to have their infant participate for the duration
of the study visits and follow-up.
8. 
Parent(s)/guardian must have a means to be contacted.
9. 
The parent(s)/guardian must pass the Test of Understanding (TOU) (Appendix 1) (see
Section 16.1).
Note: If the parent(s)/guardian fails the TOU test on the first attempt, he/she must be
retrained on the purpose of the study and must take the test again (2 repeats are allowed).
If he/she fails on the third attempt, they should not continue with screening or consenting
procedures.
4.1.2. 
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from
participating in the study:
1. 
Having received any candidate or other Ebola vaccine.
2. 
History of EVD, or prior exposure to Ebola virus, including travel to an area with a
current Ebola outbreak less than 1 month prior to screening.
3. 
Having received any experimental candidate Ad26- or MVA-based vaccine in the past.
Note: Receipt of any approved vaccinia/smallpox vaccine or experimental Ad-vector
vaccine other than Ad26 prior to study entry is allowed.
4. 
Criterion modified per Amendment 2
4.1 
Known allergy or history of anaphylaxis or other serious adverse reactions to
vaccines or vaccine products (including any of the constituents of the study
vaccines [eg,polysorbate 80, ethylenediaminetetraacetic acid (EDTA) or L-
histidine for Ad26.ZEBOV vaccine; tris (hydroxymethyl)-amino methane

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(THAM) for MVA-BN-Filo vaccine and Neisseria meningitidis polysaccharide
or tetanus toxoid for MenACWY]), including known allergy to chicken or egg
proteins and aminoglycosides (gentamicin).
5. 
Criterion modified per Amendment 2
5.1 
Presence of acute illness (this does not include minor illnesses such as mild
diarrhea or mild upper respiratory tract infection) or axillary temperature ≥37.5ºC
onDay 1. Participants with such symptoms will be excluded from enrollment at
that time but may be rescheduled for enrollmentatalater date.
6. 
Weight-for-age z-scores below -2 standard deviations of normal for age according to
the WHO growth charts (<1-year-olds).21
7. 
Having been vaccinated with any live-attenuated vaccine within 30 days before the first
vaccination, and with any inactivated vaccine within 15 days before the first
vaccination.
Note: Study intervention administration may be rescheduled to allow for infants to
receive their routine immunizations and be able to participate in this study.
8. 
Major congenital anomalies or known genetic disorders, which in the opinion of the
investigator or other delegated individual would increase the risk of an adverse outcome
from participation in the study.
9. 
Infant lives in an orphanage or other institution.
10. 
Significant prematurity or antenatal, perinatal, or early postnatal complications as
judged by the investigator or other delegated individuals.
11. 
Clinically significant history of skin disorder (eg, psoriasis, contact dermatitis), allergy,
symptomatic immunodeficiency, cardiovascular disease, respiratory disease, endocrine
disorder, liver disease, renal disease, gastrointestinal disease, neurological illness as
judged by the investigator or other delegated individual.
12. 
Criterion modified per Amendment 2
12.1 Any of the following laboratory abnormalities at screening:
 
Hemoglobin <9.0 g/dL
 
Platelet count <100 x 109/L
 
White blood cell count <5.0 x 109/L
13. 
Received a blood transfusion or other blood products within 8 weeks of screening.
14. 
Any other finding which in the opinion of the investigator or other delegated individual
would increase the risk of an adverse outcome from participation in the study.

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Clinical Protocol Amendment 4VAC52150EBL2005
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NOTE: Investigators should ensure that all study enrollment criteria have been met at screening.
If a participant’s clinical status changes (including receipt of additional medical records) after
screening but before the first vaccination (Day 1) is given such that he or she no longer meets all
eligibility criteria, then the participant should be excluded from participation in the study.
4.2. 
Extension Phase
Screening for eligible participants will be performed within 28 days before administration of the
study intervention.
The inclusion and exclusion criteria for enrolling participants in the extension phase of the study
are described in the following 2 subsections. If there is a question about the inclusion or exclusion
criteria below, the investigator must consult with the appropriate sponsor representative and
resolve any issues before enrolling a participant in the extension phase of the study. Waivers are
not allowed.
Note: Participants need to confirm their informed consent for participation in the extension phase.
4.2.1. 
Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1. 
Prior enrollment in the control arm of the main study and did not withdraw consent, and
receipt of at least the first vaccination (Dose 1) in the main study.
2. 
Parent(s) (preferably both if available or as per local requirements)/guardian must sign an
ICF indicating that he or she understands the purpose of, and procedures required for the
extension phase of the study, and potential risks and benefits of the extension phase of
the study and are willing to allow their child to participate in the extension phase of the
study.
3. 
Parent(s)/guardian are willing/able to ensure that their child adheres to the prohibitions
and restrictions specified in this protocol (see Section 4.3).
4. 
The parent(s)/guardian must be at or above the age of legal consent in the jurisdiction in
which the study is taking place.
5. 
Child must be healthy in the investigator’s clinical judgment (and the parent(s)/guardian)
on the basis of clinical assessment and clinical laboratory tests performed at screening.
Note: The safety laboratory assessments at screening are to be performed within 28 days
prior to the first vaccination on Day 1 (including Day 1 before vaccination) of the
extension phase and may be repeated if they fall outside this time window.
Note: If laboratory screening tests are out of range and deemed clinically significant,
repeating screening tests to assess eligibility is permitted once during the screening
period, using an unscheduled visit.

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Note: Collection of a baseline serum sample for future testing in the event a case of TTS
is reported, will not be required. Collection of blood from children that is unlikely to be
analyzed, is contrary to conduct of studies in children and unlikely to be approved by
Ethics Committees.
6. 
Parent(s)/guardian is available and willing to have their child participate for the duration
of the study extension phase visits and follow-up.
7. 
Parent(s)/guardian must have a means to be contacted.
8. 
The parent(s)/guardian must pass the Test of Understanding (TOU) (Appendix 1) (see
Section 16.1).
Note: If the parent(s)/guardian fails the TOU test on the first attempt, he/she must be
retrained on the purpose of the extension phase and must take the test again (2 repeats
are allowed). If he/she fails on the third attempt, they should not continue with screening
or consenting procedures.
4.2.2. 
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from
participating in the extension phase of the study:
1. 
Having received any candidate or other Ebola vaccine.
2. 
History of EVD, or prior exposure to Ebola virus, including travel to an area with a
current Ebola outbreak less than 1 month prior to screening.
3. 
Having received any experimental candidate Ad26- or MVA-based vaccine in the past.
Note: Receipt of any approved vaccinia/smallpox vaccine or experimental Ad-vector
vaccine other than Ad26 prior to study entry is allowed.
4. 
Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines
or vaccine products (including any of the constituents of the study vaccines
[eg,polysorbate 80, ethylenediaminetetraacetic acid (EDTA) or L-histidine for
Ad26.ZEBOV vaccine; tris (hydroxymethyl)-amino methane (THAM) for MVA-BN-
Filo vaccine, including known allergy to chicken or egg proteins and aminoglycosides
(gentamicin).
5. 
Presence of acute illness (this does not include minor illnesses such as mild diarrhea or
mild upper respiratory tract infection) or axillary temperature ≥37.5ºC on  Day 1.
Participants with such symptoms will be excluded from enrollment at that time but may
be rescheduled for enrollmentatalater date.

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41
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6. 
Weight-for-age z-scores below -2 standard deviations of normal for age according to
the WHO growth charts.21
7. 
Having been vaccinated with any live-attenuated vaccine within 30 days before the first
vaccination in the extension phase of the study, and with any inactivated vaccine within
15 days before the first vaccination in the extension phase of the study.
Note: Study intervention administration may be rescheduled to allow for infants to
receive their routine immunizations and be able to participate in this study.
8. 
Major congenital anomalies or known genetic disorders, which in the opinion of the
investigator or other delegated individual would increase the risk of an adverse outcome
from participation in the study.
9. 
Child lives in an orphanage or other institution.
10. 
Clinically significant history of skin disorder (eg, psoriasis, contact dermatitis), allergy,
symptomatic immunodeficiency, cardiovascular disease, respiratory disease, endocrine
disorder, liver disease, renal disease, gastrointestinal disease, neurological illness as
judged by the investigator or other delegated individual.
11. 
Any of the following laboratory abnormalities at screening:
 
Hemoglobin <9.0 g/dL
 
Platelet count <100 x 109/L
12. 
Received a blood transfusion or other blood products within 8 weeks of screening.
13. 
Any other finding which in the opinion of the investigator or other delegated individual
would increase the risk of an adverse outcome from participation in the study.
14. 
History 
of 
any 
thrombotic 
disorder, 
thrombocytopenia, 
heparin-induced
thrombocytopenia and thrombosis (HITT) or TTS.
NOTE: Investigators should ensure that all study extension phase enrollment criteria have been
met at screening. If a participant’s clinical status changes (including receipt of additional medical
records) after screening but before the first vaccination in the extension phase (eDay 1) is given
such that he or she no longer meets all eligibility criteria, then the participant should be excluded
from participation in the extension phase of the study.
4.3. 
Prohibitions and Restrictions
Parent(s)/guardian must be willing and able to adhere to the following prohibitions and restrictions
during the course of the study for their child to be eligible for participation:
1. 
In case of a new Ebola outbreak: participants and parent(s)/guardian must not travel to
an area with Ebola outbreak while the participant is enrolled in the study from the start
of screening onwards until the 21-day post-dose-2 visit. Ifapplicable, any traveling to

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Approved, Date: 28 September 2021
an area with Ebola outbreak should be documented in the case report form (CRF). The
date of travel and the destination should be clearly identified.
2. 
Ensure that their infant does not use any disallowed concomitant therapies as described
in Section 8.
Currently, no COVID vaccine is licensed for use in this pediatric age group. During the course of
the study, vaccinations may become recommended for this age group. In that case, at least 30 days
should elapse between administration of any Ad-based COVID vaccine and Ad26.ZEBOV to
avoid any confounding 'carry-over' of adverse events from one vaccine to another. At least 2 weeks
should elapse between any mRNA based COVID vaccine and Ad26.ZEBOV.
5. 
INTERVENTION ALLOCATION AND BLINDING
Procedures for Randomization and Stratification
Central randomization will be implemented in this study. Participants will be randomly assigned
to 1 of 2 intervention arms 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 country and age group. The interactive web
response system (IWRS)will assign a unique intervention code, which will dictate the intervention
assignment and matching study intervention 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.
Blinding
Main Study
The investigator will not be provided with randomization codes. The codes will be maintained
within the IWRS, which has the functionality to allow the investigator to break the blind for an
individual participant.
Data that may potentially unblind the intervention assignment (ie, study intervention preparation/
accountability data, or other specific laboratory data) will be handled with special care to ensure
that the integrity of the blind is maintained and the potential for bias is minimized. This can include
making special provisions, such as segregating the data in question from view by the investigators,
clinical team, or others as appropriate until the time of interim database lock and unblinding. The
pharmacy and preparation of study intervention  will be monitored by an independent study
intervention monitor (see Section 17.9).
Under normal circumstances, the blind should not be broken until all participants have completed
the main study and the database is locked. The investigator may in an emergency determine the
identity of the intervention  by contacting the IWRS. While the responsibility to break the
intervention 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

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available 24hours 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. The documentation received from the IWRS  indicating the code break must be
retained with the participant’s source documents in a secure manner.
Participants who have had their intervention assignment unblinded should continue to return for
scheduled evaluations.
In general, randomization codes will be disclosed fully only if the last participant has completed
the last visit of the main study (follow-up visit 12 months post-dose-1) or has left the main study
and the clinical database is locked.
If the randomization code is broken by the investigator or the study-site personnel, the participant
must discontinue further study intervention administration and must be followed as appropriate
(see Section 10.2 for details). If the randomization code is broken by the sponsor for safety
reporting purposes, the participantshould not discontinue further study intervention administration
and may remain in the study (if the randomization code is still blinded to the study-site personnel
and the participant).
When a participant withdraws before completing the study, the reason for withdrawal is to be
documented in the CRF and in the source document. Study intervention assigned to the withdrawn
participant may not be assigned to another participant. For participants who withdraw from the
study after randomization but before the first vaccination, an additional participant will be enrolled
who will receive the same vaccination regimen as the withdrawn participant. Participants who
withdraw from the study after receiving the first vaccination will not be replaced.
Extension Phase
The extension phase for participants enrolled in the control arm of the main study, will be open
label.
6. 
DOSAGE AND ADMINISTRATION
An overview of the study vaccination schedule is provided in Table 2.
Table 2: 
Study Vaccination Schedule (Main Study)
N 
(per arm) 
Dose 1 
(D1) 
Dose 2 
(D57) 
Third vaccination
(6 months post-dose-2)
73 
Ad26.ZEBOV 5x1010 vp 
MVA-BN-Filo 1x108 Inf U  
MenACWY
34 
MenACWY 
MenACWY  
MenACWY
All participants randomized to the Ad26.ZEBOV, MVA-BN-Filo arm will receive the following
study vaccines as a 0.5-mL IM injection into the anterolateral thigh:
- Ad26.ZEBOV: 5x1010 vp on Day 1
- MVA-BN-Filo: 1x108 Inf U on Day 57

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Participants in the control arm will receive the WHO-prequalified MenACWY as Dose 1 on Day 1,
as Dose 2 on Day 57.
The recommended immunization series of MenACWY consists of 2 doses given 2 months apart,
followed by a booster dose at 12 months of age. Previously unvaccinated children may receive a
single dose in their second year of life. In keeping with the recommended immunization regimen
for this vaccine, all participants will receive a dose of MenACWY at the 6-months post-dose-2
visit. The MenACWY vaccine will be administered as a 0.5-mL IM injection into the anterolateral
thigh.
Upon completion of the main study, participants in the extension phase who were originally
randomized to the control arm will receive the same vaccine regimen as the participants in the
Ad26.ZEBOV, MVA-BN-Filo arm of the main study.
In the main study, study intervention will be prepared by an unblinded pharmacist or qualified
staff member with primary responsibility for study intervention preparation and dispensing, and
who is not involved in any other study-related procedures. Participants will be administered the
study intervention in a masked syringe in a way that maintains double-blinding.
In the extension phase, the preparation of the study intervention will be unblinded.
In the main study, Ad26.ZEBOV, MVA-BN-Filo, or MenACWY will be administered as 0.5-mL
IM injections in the anterolateral thigh, by a blinded study intervention  administrator.
In the extension phase, the study intervention administrator will be unblinded, and the vaccine may
be administered IM either into the deltoid muscle or in the anterolateral thigh.
The injection site should be free from any injury, local skin conditions, or other issue that might
interfere with the evaluation of local reactions. In each participant, the second vaccination should
be administered in the opposite leg from the first vaccination (unless the opposite leg has a
condition that prevents evaluating the leg after injection) and it should be recorded in the CRF in
which leg the vaccination has been administered. The vaccination at 6 months post-dose-2 can be
administered in either leg. No local or topical anesthetic will be used prior to the injection.
Discontinuation of study intervention administration should occur in any participant meeting the
criteria outlined in Section 10.2. Criteria for postponement of vaccination and contraindications to
the second vaccination  and MenACWY vaccination  at 6 months post-dose-2 are defined in
Sections 6.1 and 6.2, respectively. Refer to Section 9.3.2 for details on the pre-specified pausing
rules to halt vaccination of further participants.
Participants will remain at the site for at least 30 minutes after each vaccination for presence of
any acute reactions, or longer if deemed necessary by the investigator (eg, in case of grade 3
adverse events). As with any vaccine, allergic reactions following vaccination with the study
intervention  are possible. Therefore, appropriate drugs and medical equipment to treat acute
anaphylactic reactions must be immediately available and a medically qualified member of study-
site personnel trained to recognize and treat anaphylaxis must be present in the clinic during the
entire vaccination procedure and post-vaccination monitoring period.

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The investigator must provide emergency care as needed for any participant who experiences a
life-threatening event. All sites will have facilities, equipment and the ability to manage an
anaphylactic reaction. If additional therapy is required, the investigator will arrange for transport
to the closest appropriate facility for continuing care.
The Site Investigational Product Procedures Manual specifies the maximum time that will be
allowed between preparation and administration of the study intervention.
Ad26.ZEBOV and MVA-BN-Filo will be manufactured and provided under the responsibility of
the sponsor. Refer to the Investigator's Brochure for a list of excipients.14
6.1. 
Criteria for Postponement of Vaccination
A participant will not be given any vaccination if he/she experiences any of the following events
at the scheduled time for vaccination:
- Acute illness at the time of vaccination (this does not include minor illnesses such as diarrhea
or mild upper respiratory tract infection);
- Axillary temperature ≥37.5°C at the time of vaccination.
Participants experiencing any of the events described above may be vaccinated up to 10 days
beyond the window allowed for the scheduled vaccination or be withdrawn from that vaccination
at the discretion of the investigator and after consultation with the sponsor.
Note: In case the second vaccination is postponed, the timing of the post-dose-2  visits will be
planned relative to the actual vaccination day.
6.2. 
Contraindications to SecondVaccination and 6-months Post-dose-2
Vaccination
A participant will not be given the second vaccination or the MenACWY vaccination at 6 months
post-dose-2 if he/she experiences any of the following events at any time after the first vaccination:
1. Anaphylaxis clearly attributable to vaccination with study intervention; OR
2. Generalized urticaria within 24hours of vaccination  considered to be related to study
intervention; OR
3. A serious adverse event considered to be related to study intervention; OR
4. Injection site ulceration, abscess,or necrosis considered to be related to study intervention; OR
5. Any other safety concern threatening the participant’s safety.
Participants experiencing any of the events described above must not receive any further study
intervention but should be monitored for safety and for immunogenicity according to the protocol.

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7. 
INTERVENTION COMPLIANCE
In the main study, study intervention will be administered as an IM injection by blinded qualified
study-site personnel at the study site. Details of each administration will be recorded in the CRF
(including date and time of injection and thigh used for injection). For blinding procedures, see
Section 5. In the extension phase, study intervention will be administered by unblinded qualified
study-site personnel.
8. 
PRESTUDY AND CONCOMITANT THERAPY
Prestudy therapies administered up to 30 days prior to the start of screening and previous
vaccinia/smallpox vaccination at any time prior to study entry must be recorded in the CRF at
screening for the main study.
Infants in the main study and children in the extension phase must receive all routine
immunizations appropriate for their age according to local routine vaccination schedules, taking
into consideration the following restrictions. A participant should not receive a live-attenuated
vaccine from 30 days before the first vaccination until 30 days after the second vaccination unless
a vaccine preventable disease such as measles emerges which would warrant administration of
live-attenuated vaccines. Immunizations with inactivated vaccines should be administered at least
15 days before or after administration of any study intervention in order to avoid any potential
interference in efficacy of the routine immunizations or the interpretation of immune responses to
study intervention, as well as to avoid potential confusion with regard to attribution of adverse
reactions. However, if a vaccine is indicated in a post-exposure setting (eg,rabies or tetanus), it
must take priority over the study intervention. Otherwise, a participant will not postpone, forego,
or delay the receipt of any recommended vaccine according to local schedules (eg, EPI schedule
according to the WHO regional office for West Africa). Prior to vaccination of infants in the main
study and children in the extension phase, parent(s)/guardian will be asked to show the child’s EPI
vaccination card to check that the child has not received a live-attenuated vaccine within the last
30 days. In case the parent(s)/guardian does not have a card or cannot show it, the participant will
be excluded from the study.
Considering the COVID-19 situation, administration of COVID-19 vaccine should follow the
national guidelines and schedule. COVID-19 vaccine may be prioritized or intercalated with Ebola
vaccination according to national guidance by authorities. Recombinant viral vectored COVID-19
vaccines or live attenuated COVID-19 vaccines, either licensed or authorized for emergency use
(eg, Emergency Use Authorization [EUA], Emergency Use Listing [EUL] or similar program) 
should not be administered within 30 days before or after planned administration of the study
intervention. Other COVID-19 vaccines that are not viral vectored, or are not live attenuated, (eg,
mRNA vaccines, protein-based vaccines) either licensed or authorized for emergency use (eg,
EUA, EUL or similar program) should not be administered within 15 days before or after planned
administration of the study intervention.
Note: National Immunization Plans will be available on site and these will be taken into
consideration when planning vaccination schedules. Study intervention administration may be

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rescheduled to allow for infants to receive their routine immunizations and be able to participate
in this study.
Analgesic/antipyretic medications and non-steroidal anti-inflammatory drugs may be used post-
vaccination in case of medical need (eg,fever or pain). Use of these medications as routine
prophylaxis prior to study intervention  administration is not recommended. The use of these
medications must be documented.
Concomitant therapies must be recorded from screening onwards until 28 days post-dose-1 and
from the second vaccination until 28 days post-dose-2. At the other time points, they should only
be recorded if given in conjunction with serious adverse events. Information on concomitant use
of herbal supplements or vitamins will not be collected, except for the use of vitamin A
supplementation, which will be collected.
Use of any experimental medication (including experimental vaccines other than the study
intervention) during the study is not allowed.
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in
which prohibited therapies are administered.
9. 
STUDY EVALUATIONS
9.1. 
Study Procedures
9.1.1. 
Overview
The Time and Events Schedule summarizes the frequency and timing of safety  and
immunogenicity  measurements applicable to this study. Details for all study procedures are
provided in the following sections. Additional unscheduled study visits may be required if in the
investigator’s opinion, further clinical or laboratory evaluation is needed.
Visit Windows
Visit windows are provided in the Time and Events Schedule. If a participant did not receive study
intervention on the planned day of vaccination, the timings of the next visits post-vaccination will
be determined relative to the actual day of vaccination. The participant should be encouraged to
come within these windows.
Blood Sampling Volume
Main Study
The total blood volume for the main study is 8.0-9.5 mL: 2.0 mL for safety and 6.0-7.5 mL for
immunogenicity  depending on the most successful phlebotomy method, either the direct
(vacutainer) method or indirect (syringe) method. If the indirect (syringe) method is chosen, the
immunogenicity blood sample is 2.0 mL per visit and the total blood volume is 8 mL. If the direct
(vacutainer) method is chosen, then the immunogenicity blood sample is 2.5 mL per visit and the

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total blood volume is 9.5 mL. Whenever feasible, a single phlebotomy method will be used for a
given subject.
The maximum amount of blood that will be drawn on a single visit is 3.5 mL. The study-related
blood volumes obtained (including any losses during phlebotomy) will not exceed 3% of the total
blood volume during a period of 4 weeks and will not exceed 1% at any single time. The total
volume of blood is estimated at 80 to 90 mL/kg body weight; 3% is 2.4 mL blood per kg body
weight.9 The allowable blood volume calculations are based on the 10th percentile for growth
charts for infants.21
Extension Phase
In the extension phase a total blood volume of 2.0 mL will be drawn  for safety laboratory
assessments, ie,1 mL at screening and 1 mL prior to administration of MVA-BN-Filo.
In the unlikely event that a TTS event should occur after Dose 1 administration, pre-existing anti-
PF4 antibodies may be assessed in the baseline serum of the participant.
For details on the approximate blood sampling volumes collected by visit and the cumulative blood
volumes, refer to the Time and Events Schedule.
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the
samples.
9.1.2. 
Screening Period
Main Study
Up to 28 days before baseline (Day 1, day of first vaccination) and after signing and dating the
ICF (see Section 16.2.3), screening assessments will be performed as indicated in the Time and
Events Schedule. Screening may be split into multiple days or visits.
Only participants complying with the criteria specified in Section 4will be included in the study.
The investigator will provide detailed information on the study to the parent(s)/guardian of the
infant and will obtain written informed consent from them prior to study participation of the infant.
After reading but before signing the ICF, the TOU will be administered to the parent(s)/guardian.
Parent(s)/guardian who fail may repeat the test twice (and have to pass the third time for their child
to be eligible) (for details, see Section 16.1).
The overall eligibility of the participant to participate in the study will be assessed once all
screening values and results of any other required evaluations are available. Retesting of values
(eg, safety laboratory, weights that are at the borderline of the z-scores at screening) that lead to
exclusion is allowed once using an unscheduled visit during screening to assess eligibility. If
rescreening is required, all screening procedures (except TOU) should be repeated. Study
participants who qualify for inclusion will be contacted and scheduled for enrollment and first
vaccination within 28 days.

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A serum sample will be taken at screening, to serve as pre-vaccination baseline sample for
immunogenicity assessments (see Section 9.4).
Extension Phase
For participation in the extension phase of the study, a separate ICF and TOU will need to be
signed. The screening procedures are the same as in the main study, except that no serum sample
will be taken at screening to serve as pre-vaccination baseline sample for immunogenicity
assessments.
9.1.3. 
Vaccination Period
If eligible, the participant will come for the baseline visit (Day 1). The investigator should ensure
that all enrollment criteria have been met during screening. If a participant’s clinical status changes
(including available laboratory results or receipt of additional medical records) after screening but
before the first vaccination (Day 1) such that he/she no longer meets all enrollment criteria, then
the participant should be excluded from further participation in the study.
Eligible participants will be allocated to an intervention arm as described in Section 5. Before each
vaccination, a brief physical examination (including body length and weight) and measurement of
vital signs will be performed.
Participants will be vaccinated as described in Section 6. After each vaccination, participants will
remain under observation at the study site for at least 30 minutes for presence of any acute
reactions, or longer if deemed necessary by the investigator. Following the first and second
vaccination, any unsolicited, solicited local or systemic adverse events, and vital signs will be
documented by study-site personnel at the end of this observation period.
Upon discharge from the site, parent(s)/guardian will be provided with a thermometer (to measure
body temperature), a ruler (to measure local injection site reactions), and a participant diary to
record body temperature and solicited local (at injection site) and systemic symptoms and will be
trained on how to collect this information. Symptoms of solicited local and systemic adverse events
will be collected in the diary in the evening after the first and second vaccination and then daily
for the next 7 days at approximately the same time each day. Diaries will be completed at home
by either a project field worker who will visit the participant during daily visits or by the
parent(s)/guardian and checked by a project field worker. The investigator or clinical designee will
review information from the participant’s diary.
Participants will come to the site at 7 days after the first and second vaccination as indicated in the
Time and Events Schedule. The participant’s diary will be reviewed by study-site personnel. The
investigator will examine the injection site for occurrences of erythema, swelling, or tenderness at
these visits in order to complete the relevant parts of the CRF.
Unsolicited adverse events will be reported from the first vaccination until 28 days post-dose-1,
and from the second vaccination until 28 days post-dose-2.

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Serious adverse events and/or special reporting situations that are related to study procedures or
that are related to non-investigational (concomitant) sponsor products will be reported from the
time a signed and dated ICF is obtained onwards until the end of the study. All other serious
adverse events and/or special reporting situations will be reported from the day of first vaccination
onwards until 6 months post-dose-2 for the main study, and for 28 days post-dose-2 for the
extension phase.
Participants will come to the site at 21 days after the second vaccination  for safety and
immunogenicity assessments. Refer to Section 9.4for details on the immunogenicity evaluations.
In the main study, the parent(s)/guardian will be instructed to contact the investigator before the
next visit (ie, 6 months post-dose-2) if their child experiences any adverse event or intercurrent
illness that they perceive as relevant and/or can be possibly related to study intervention in their
opinion.
All participants will receive a dose of MenACWY at 6 months post-dose-2 in the main study as
described in Section 6. After vaccination, participants will remain under observation at the study
site for at least 30 minutes for presence of any acute reactions, or longer if deemed necessary by
the investigator. Vital signs will also be collected at the end of the observation period. Participant
diaries will not be distributed. Infants that experience any symptoms will be invited to come for
an unscheduled visit as needed.
No immunogenicity assessments will be performed in the extension phase.
9.1.4. 
Follow-up Period
Participants of the main study will return to the study site at 12 months post-dose-1 to check for
serious adverse events related to study intervention, and to collect a blood sample for
immunogenicity assessments (see Section 9.4).
9.2. 
Procedures in Case of a Study Pause
A study pause can affect participants that are either awaiting the first or second vaccination. After
approval is granted to restart the study, participants who are awaiting the first vaccination and
whose screening period is longer than the protocol-defined 28 days as a result of a study pause,
will be allowed to rescreen once (following the screening procedures described in Section 9.1.2,
excluding TOU). Participants that are rescreened due to a pause must have new safety laboratory
assessments (including full blood count, physical examination, and vital signs) within 28 days of
the first vaccination. The TOU does not need to be repeated. After screening, these participants
will follow the same study procedures as those participants who were unaffected by a study pause
(described in Section 9.1.3).
Participants who are outside the protocol-defined second vaccination window due to a study pause
will be offered a late second vaccination (if allowed by the sponsor and/or the relevant oversight
authorities). Participants who will receive a late second vaccination will follow the same post-
dose-2 vaccination schedule as those participants whose second vaccination was unaffected by a

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study pause (see Section 9.1.3). In case the second vaccination is postponed, the timing of the post-
dose-2 visits will be planned relative to the actual vaccination day.
9.3. 
Safety Evaluations
9.3.1. 
Safety Assessments
The investigators, together with the sponsor’s medical monitor, will be responsible for the safety
monitoring of the study, and will halt vaccination of further participants in case any of the
pre-specified pausing rules described in Section 9.3.2 have been met. Further safety measures with
regards to vaccination are described in Sections 6.1 and 6.2.
An IDMC will be appointed by the sponsor before the start of the main study to perform regular
review of the safety data during the study. Details regarding the IDMC are provided in
Section 11.7. In the extension phase, the IDMC will be replaced by an independent medical
reviewer. Details regarding the independent medical reviewer are provided in Section 11.8.
Symptoms of solicited local and systemic adverse events will be collected in the diary in the
evening after the first and second vaccination and then daily for the next 7 days. Unsolicited
adverse events will be collected from the first vaccination until 28 days post-dose-1, and from the
second vaccination  until 28 days post-dose-2. Serious adverse events and/or special reporting
situations that are related to study  procedures or that are related to non-investigational
(concomitant) sponsor products will be reported from the time a signed and dated ICF is obtained
onwards until the end of the study phase (main and extension phase). All other serious adverse
events and/or special reporting situations will be reported from the day of the first vaccination
onwards until 6 months post-dose-2 in the main study, and until 28 days post-dose-2 in the
extension phase.
Any clinically relevant changes must be recorded on the Adverse Event section of the CRF.
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.
All AEs will be coded for severity according to the criteria presented in Section 12.1.3.
The study will include the following evaluations of safety and reactogenicity according to the time
points provided in the Time and Events Schedule:
Adverse Events
Adverse events will be reported as specified in Section 12.3.1.
Solicited Adverse Events
After each vaccination, participants will remain under observation at the study site for at least
30 minutes for presence of any acute reactions, or longer if deemed necessary by the investigator.
Symptoms of solicited local and systemic adverse events will be collected in the diary in the
evening after the first and second vaccination and then daily for the next 7 days. Diaries will be

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completed at home by either a project field worker who will visit the participant during daily visits
or by the parent(s)/guardian and checked by a project field worker. Diary information will be
transcribed by the study personnel in the diary CRF pages. Once a solicited symptom from a diary
is considered to be of severity Grade 1 or above, it will be referred to as a solicited adverse event.
Solicited Injection Site (Local) Adverse Events
Parents/guardians (or the project field worker) will be asked to note in the diary occurrences of
tenderness, erythema and swelling at the study intervention injection site daily for 7 days post-
vaccination (day of vaccination and the subsequent 7 days). The extent (largest diameter) of any
erythema, and swelling should be measured (using the ruler supplied) and recorded daily.
 
Injection Site Tenderness
Injection site tenderness is a painful sensation localized at the injection site upon palpation or
movement of the limb. Due to subjective nature of the reaction, the severity assessment of
tenderness is self-reported (if a participant is unable to provide self-report, other reporters
include parent/care giver or health care provider).11
 
Injection Site Erythema
Injection site erythema is a redness of the skin caused by dilatation and congestion of the
capillaries localized at the injection site. It can best be described by looking and measuring.
 
Injection Site Swelling
Injection site swelling is a visible enlargement of an injected limb. It may be either soft
(typically) or firm (less typical).
Note: Any other injection site events not meeting the above case definitions should be reported
separately as unsolicited AEs.18
Solicited Systemic Adverse Events
Parent(s)/guardian  will be instructed on how to record daily temperature using a thermometer
provided for home use. The axillary temperature of the participant should be recorded in the diary
in the evening of the day of vaccination, and then daily for the next 7 days at approximately the
same 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 CRF.
Fever is defined as endogenous elevation of body temperature ≥38° C, as recorded in at least one
measurement.19
Parent(s)/guardian will also be instructed on how to note daily in the diary symptoms for 7 days
post-vaccination (day of vaccination and the subsequent 7 days) of the following events: loss of
appetite, vomiting, diarrhea, decreased activity, irritability.

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Physical Examination
A brief, symptom-directed examination (including body length and weight) will be performed
based on any clinically relevant issues, clinically relevant symptoms and medical history. The
symptom-directed physical examination may be repeated if deemed necessary by the investigator.
Physical examinations will be performed by the investigator or by a designated medically-trained
clinician. Physical examination findings (ie, abnormalities) prior to Dose 1 vaccination are to be
recorded as medical history, after Dose 1 vaccination as adverse event.
Vital Signs
Axillary temperature, pulse/heart rate (beats per minute), and respiratory rate (breaths per minute)
will be assessed.
Pulse/heart rate measurements will be assessed with a completely automated device. Manual
techniques will be used only if an automated device is not available. Pulse/heart rate measurements
should be preceded by at least 5 minutes of rest in a quiet setting without distractions.
Clinical Laboratory Tests
Samples will be collected for hematology. The investigator must review the laboratory report,
document this review, and record any clinically relevant changes on the adverse event page of the
CRF. Laboratory reports must be filed with the source documents.
A full blood count will be performed by the local laboratory at the time points indicated in the
Time and Events Schedule:
-hemoglobin
-hematocrit
-red blood cell (RBC) count
-white blood cell (WBC) count with differential
-platelet count
Note: a WBC evaluation may include any abnormal cells, which will then be reported by the laboratory. A RBC
evaluation may include abnormalities in the RBC count, or RBC morphology, which will then be reported by
the laboratory.
In addition, any other abnormal cells in a blood smear will also be reported.
9.3.2. 
Study Pausing Rules
The investigators and the sponsor’s medical monitor will review the safety of enrolled participants
on an ongoing basis and will halt vaccination of further participants in case any of the pre-specified
pausing rules described in this section are met. The sponsor’s medical monitor will be involved in
all discussions and decision. These pausing rules are not applicable for the vaccination with
MenACWY at 6 months post-dose-2.
If any of the following events occur in any participant who received at least one dose of study
intervention in the study (at any site), the site investigator will halt the vaccination of further
participants in this study and the sponsor’s medical monitor will be notified immediately. The
sponsor’s medical monitor will inform all the other investigators to halt further vaccination as well.

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1. Death of a participant, considered related to study intervention or if the causal relationship to
the study intervention cannot be excluded; OR
Note: All cases of death will be sent for IDMC information. Upon their review, IDMC may
then also decide whether a study pause is required.
2. One or more participants experience a life-threatening or serious adverse event (solicited or
unsolicited) that is determined to be related to study intervention; OR
3. One or more participants experience anaphylaxis or generalized urticaria within 24hours of
vaccination, clearly not attributable to other causes than vaccination with study intervention;
OR
4. Two or more participants experience a grade 3 or 4 unsolicited adverse event of the same type
(as per medical judgment of the sponsor), that is determined to be related to study intervention;
OR
5. Two or more participants experience a grade 3 or 4 solicited systemic adverse event of the
same type, determined to be related to study intervention, and persisting for 3 or more daysa.
OR
6. Two or more participants experience a grade 3 or 4 local adverse event (including injection
site ulceration, abscess or necrosis) of the same type, and persisting for 3 or more days.
For numbers 4, 5, and 6: after each IDMC review of similar adverse events, the Committee will
indicate the conditions under which it requires further notification and review of the subsequent
similar adverse events.
To enable prompt response to a situation that could trigger pausing rules, the investigator should
notify the sponsor’s medical monitor or designee (AND fax or email serious adverse event form
to Global Medical Safety Operations, if applicable), immediately and no later than 24 h after
becoming aware of any related adverse event of grade 3 or above AND update the CRF with
relevant information on the same day the adverse event information is collected. A thorough
analysis of all grade 3 cases will be carried out by the sponsor’s medical monitor or designee,
irrespective of whether the criteria for pausing the study are met. Based on the pausing criteria, the
sponsor’s medical monitor or designee then decides whether a study pause is warranted. All
investigators will be notified immediately in case of a study pause. The sponsor’s medical monitor
or designee is responsible for the immediate notification of IDMC members and coordination of
an IDMC meeting in case of a study pause.
Vaccinations for an individual participant may be suspended for safety concerns other than those
described in the pausing criteria, at the discretion of the investigator if he/she feels the participant’s
safety may be threatened. The sponsor’s medical monitor or designee or the investigator(s) (upon
consultation with the sponsor’s medical monitor or designee) may initiate IDMC review for any
a The day of occurrence ofthe adverse event is counted as Day 1.

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single event or combination of multiple events which, in their professional opinion, could
jeopardize the safety of the participants or the reliability of the data.
Vaccinations for the study may be suspended for safety concerns other than those described above,
or before pausing rules are met, if, in the judgment of the IDMC, participant safety may be
threatened.
Resumption of vaccinations will start only upon receipt of written recommendations by the IDMC.
The clinical site(s) will be allowed to resume activities upon receipt of a written notification from
the sponsor. The communications from the IDMC will be forwarded by the investigator to the
Independent Ethics Committee (IEC)/Institutional Review Board (IRB) and by the sponsor to the
relevant health authorities, according to local standards and regulations.
In the extension phase of the study, the IDMC will be replaced by an independent medical reviewer
(see Section 11.8).
9.4. 
Immunogenicity Assessments
In the main study, venous blood samples (2.0-2.5 mL) for the determination of immune responses
will be collected at the time points indicated in the Time and Events Schedule. Serum will be used
for the following assessments:
- Analysis of binding antibodies against EBOV GP (FANG ELISA): to determine humoral
responses following vaccination.
- Analysis of neutralizing antibody response against the adenovirus backbone (Ad26 VNA):
to explore baseline neutralizing antibody responses against the vector in the study
population.
Sample collection and processing will be performed by the study-site personnel according to
current versions of approved standard operating procedures. The Laboratory Manual contains
further details regarding the collection, handling, labeling, and shipment of blood samples to the
respective laboratories.
During the extension phase, no blood samples for immunogenicity evaluations will be collected.
9.5. 
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the CRF or laboratory
requisition form.
Refer to the Time and Events Schedule 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.

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10. 
PARTICIPANT COMPLETION/DISCONTINUATION OF STUDY
INTERVENTION/ WITHDRAWAL FROM THE STUDY
10.1. Completion
Main Study
A participant will be considered to have completed the main study if he or she has completed all
assessments at the 12-months post-dose-1 visit.
Participants who prematurely discontinue study participation for any reason before completion of
the 12-month post-dose-1 visit will not be considered to have completed the main study.
A participant in the Ebola vaccine arm of the main study will be considered to have completed the
study if he or she has completed all assessments at the 12-months post-dose-1 visit.
Extension Phase
A participant will be considered to have completed the extension phase of the study if he or she
has completed all assessments at the 28 days post-dose-2 visit.
Participants who prematurely discontinue study participation for any reason before completion of
the 28 days post-dose-2 visit will not be considered to have completed the extension phase of the
study.
A participant of the extension phase will be considered to have completed the study if he or she
has completed both the main study and the extension phase.
10.2. Discontinuation of Study Intervention/Withdrawal From the Study
Discontinuation of Study Intervention
A participant will not be automatically withdrawn from the study if he or she has to discontinue
study intervention before the end of the intervention regimen.
A participant’s study intervention (dose 1 or dose 2) must be discontinued at the discretion of the
investigator and after consultation with the sponsor for any of the events in Section 6.1.
A participant’s study intervention should be permanently discontinued if:
 
The investigator believes that for safety reasons (eg,adverse event) it is in the best
interest of the participant to discontinue study intervention;
 
Confirmed EVD
 
The participant experiences any of the events described in Section 6.2;
 
The randomization code is broken by the investigator or the study-site personnel (only
applicable for main study).

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Participants meeting any of the reasons listed above must not receive any further study
intervention, but should continue to be monitored for safety and immunogenicity according to the
protocol if this does not result in safety risks for the participant. In case of early discontinuation of
study intervention due to an adverse event, the investigator will collect all information relevant to
the adverse event and safety of the participant, and will follow the participant to resolution, or until
reaching a clinically stable endpoint. In case of a study pause, participants need to follow
procedures as described in Section 9.2.
Withdrawal From the Study
Parent(s)/guardian have the right to withdraw their child from the study at any time for any reason
without affecting the right to treatment by the investigator. The investigator should make an
attempt to contact participants who did not return for scheduled visits or follow-up. Although
parent(s)/guardian are not obliged to give reason(s) for withdrawing prematurely, the investigator
should make a reasonable effort to ascertain the reason(s) while fully respecting the participant’s
rights.
A participant will be withdrawn from the study for any of the following reasons:
 
Lost to follow-up
 
Withdrawal of consent
 
Death
 
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 IEC/IRB to stop or cancel the study
If a participant is lost to follow-up, every reasonable effort must be made by the study-site
personnel to contact the participant and determine the reason for discontinuation/withdrawal. The
measures taken to follow up must be documented.
When a participant withdraws before completing the study, the reason for withdrawal is to be
documented in the CRF and in the source document. For participants who withdraw from the study
after randomization but before the first vaccination, an additional participant will be enrolled who
will receive the same vaccination regimen as the withdrawn participant. Participants who withdraw
from the study after receiving the first vaccination will not be replaced.
Participants who wish to withdraw consent from participation in the study will be offered an
optional visit for safety follow-up (prior to formal withdrawal of consent). They have the right to
refuse.
Withdrawal From the Use of Samples in Future Research
Parent(s)/guardian may withdraw consent for use of their child’s samples for research (refer to
Section 16.2.5). 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 ICF.

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11. 
STATISTICAL METHODS
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 safety and immunogenicity data is
outlined below. Specific details will be provided in the Statistical Analysis Plan (SAP).
The primary interim analysis for the blinded phase of the study will be done when all participants
have completed the 12 months post-dose-1 visit or have left the main study (ie, completion of the
main study), and the clinical database is locked and unblinded. This analysis will include all
available data up to the 12 months post-dose-1 (D365) visit.
The final analysis will be performed at study completion, defined as the date of final database lock,
which will occur after all participants have completed the last study-related visit or left the study.
11.1. Analysis Sets
Full Analysis Set: The full analysis set will include all randomized participants with at least one
study intervention  administration documented. Participants will be analyzed according to the
intervention they actually received.
Per-protocol Immunogenicity Population: The per-protocol immunogenicity population will
include all randomized and vaccinated participants for whom immunogenicity data are available
excluding participants with major protocol deviations expecting to impact the immunogenicity
outcomes (eg,missed vaccinations, natural infections, etc).
11.2. Sample Size Determination
The sample size is not based on formal hypothesis testing considerations. Active control recipients
are included for blinding purposes and safety analyses, and will provide control specimens for
immunologic assays.
The sample size for this study expands the safety and immunogenicity database for VAC52150 to
infants. While mild to moderate vaccine reactions (local/systemic responses) are expected, adverse
events that preclude further study intervention administration or more serious events that would
limit product development are not anticipated:
- When 73 infants are vaccinated with Ad26.ZEBOV, MVA-BN-Filo, the observation of
0 reactions would be associated with a 95% confidence that the true rate is less than 4.0%.
- When 34infants are vaccinated with active control, the observation of 0 reactions would
be associated with a 95% confidence that the true rate is less than 8.4%.
Table 3 provides the probabilities of observing at least one adverse event at given true adverse
event rates.

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Table 3: 
Probability of Observing at Least One Adverse Event Given a True Adverse Event Incidence
True Adverse Event Incidence (%) 
Probability of Observing at Least One Adverse Event (%)
Ad26.ZEBOV, MVA-BN-Filo 
Active Comparator
N=73 
N=34
1 
52 
29
3 
89 
64
5 
98 
83
7 
99 
92
9 
100 
96
15 
100 
100
n: number of participants
11.3. Participant Information
For all participants, demographic characteristics (eg, age, weight and length percentiles according
to WHOpediatricgrowth and weight charts,21 race, and gender), and other baseline characteristics
(eg, vital signs, concomitant diseases) will be tabulated and summarized with descriptive statistics.
11.4. Safety Analyses
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively
(including 95% CIs, if applicable) by intervention arm.
Adverse Events (Including Reactogenicity)
The verbatim terms used in the CRF by investigators to identify adverse events will be coded using
the Medical Dictionary for Regulatory Activities (MedDRA). All reported adverse events and
events-related diary information (solicited local at injection site and systemic, and unsolicited)
with onset within 28 days after the first or second vaccination (ie, intervention-emergent adverse
events) will be included in the analysis. For each adverse event, the number and percentage of
participants who experience at least 1 occurrence of the given event will be summarized by
intervention arm.
Summaries, listings, datasets, or participant narratives may be provided, as appropriate, for those
participants who die, who discontinue study intervention  due to an adverse event, or who
experience a severe or a serious adverse event.
Physical Examination
Because only abbreviated, symptom-directed examinations are performed per discretion of the
investigator, physical examination findings (ie, abnormalities) after Dose 1 vaccination are to be
recorded as adverse events, and will be analyzed and presented as indicated above. When reported
prior to Dose 1 vaccination, they will be recorded as medical history.
Baseline percentiles of body length and weight (according to WHO growth charts, see Section 4)
will be tabulated and summarized descriptively  (as part of the demographics and baseline
characteristics summaries and listings).

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Vital Signs
Descriptive statistics of temperature, pulse/heart rate, and respiratory rate values will not be
summarized at each scheduled time point. A listing of participants with clinically significant
abnormal values will be provided.
Clinical Laboratory Tests
Laboratory abnormalities will be determined according to the toxicity grading tables (see
Appendix 2), and in accordance with the normal ranges of the clinical laboratory. The most severe
laboratory abnormalities following vaccination will be listed.
11.5. Immunogenicity Analyses
No formal hypothesis on immunogenicity will be tested. Descriptive statistics (geometric mean
and 95% CI, or median and range Q1-Q3, as appropriate) will be calculated for continuous
immunologic parameters at all available time points. Graphical representations of immunological
parameters will be made as applicable. Frequency tabulations will be calculated for discrete
(qualitative) immunologic parameters as applicable.
11.6. Interim Analysis
The primary interim analysis for the blinded phase of the study will be done when all participants
have completed the 12 months post-dose-1 visit or have left the main study (ie, completion of the
main study), and the clinical database is locked and unblinded. This analysis will include all
available data up to the 12 months post-dose-1 (D365) visit.
11.7. Independent Data Monitoring Committee
An IDMC will be established to monitor data on an ongoing basis to ensure the continuing safety
of the participants enrolled in the main study.
The Committee will meet periodically to review newly generated data. Ad hoc IDMC meetings
may be requested via the sponsor for any single event or combination of multiple events which are
considered to jeopardize the safety of the participants. After the review, the IDMC will make
recommendations regarding the continuation of the study. The IDMC responsibilities, authorities,
frequency and timing of the evaluations and procedures will be documented in its charter. All
analyses that are planned to support the IDMC evaluations will be included in the associated SAP.
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.
11.8. Independent Medical Reviewer
An independent medical reviewer will be appointed before the start of the extension phase to
review the accumulating safety data on an ongoing basis to ensure the continuing safety of the
participants enrolled in the extension phase of the study.

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The independent medical reviewer will be consulted periodically to review newly generated data.
Ad hoc meetings may be requested via the sponsor if any of the pre-specified pausing rules for this
study are met (see Section 9.3.2) or in any situation that could affect the safety of the participants.
After the review, the independent medical reviewer will make recommendations regarding the
continuation of the extension  phase of the study. The independent medical reviewer
responsibilities, authorities, frequency and timing of the evaluations and procedures will be
documented in a role and responsibility description.
The independent medical reviewer will be external and independent of the sponsor. He or she will
be a medical expert in the relevant field.
12. 
ADVERSE EVENT REPORTING
Timely, accurate, and complete reporting and analysis of safety information from clinical studies
are crucial for the protection of participants, investigators, and the sponsor, and are mandated by
regulatory agencies worldwide. The sponsor has established Standard Operating Procedures in
conformity with regulatory requirements worldwide to ensure appropriate reporting of safety
information; all clinical studies conducted by the sponsor or its affiliates will be conducted in
accordance with those procedures.
Method of Detecting Adverse Events and Serious Adverse Events
Care will be taken not to introduce bias when detecting adverse events or serious adverse events.
Open-ended and nonleading verbal questioning of the participant’s parent(s)/guardian  is the
preferred method to inquire about adverse event occurrence.
Solicited Adverse Events
Solicited adverse events are predefined local (at the injection site) and systemic events for which
the participant’s parent(s)/guardian  is specifically questioned, and which are noted in the
participant’s diary.
Unsolicited Adverse Events
Unsolicited adverse events are all adverse events for which the participant’s parent/guardian is not
specifically questioned in the participant diary.
12.1. Definitions
12.1.1. 
Adverse Event Definitions and Classifications
Adverse Event
An adverse event is any untoward medical occurrence in a clinical study participant administered
a medicinal (investigational or non-investigational) product. An adverse event does not necessarily
have a causal relationship with the intervention. An adverse event 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

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to that medicinal (investigational or non-investigational) product. (Definition per International
Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use [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.
Note: For time period of sponsor’s adverse event collection, see Section 12.3.1.
Serious Adverse Event
A serious adverse event 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 were more severe.)
 
Requires inpatient hospitalization or prolongation of existing hospitalization
 
Results in persistent or significant disability/incapacity
 
Is a congenital anomaly/birth defect
 
Is a suspected transmission of any infectious agent via a medicinal product
 
Is Medically Important*
*Medical and scientific judgment should be exercised in deciding whether expedited reporting is
also appropriate in other situations, such as important medical events that may not be immediately
life threatening or result in death or hospitalization but may jeopardize the participant or may
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 adverse event occurs for which there is evidence suggesting a causal
relationship between the study intervention and the event (eg, death from anaphylaxis), the event
must be reported as a SUSAR (even after the study is over, if the sponsor, IDMC, independent
medical reviewer or investigator becomes aware of them).
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An adverse event is considered unlisted if the nature or severity is not consistent with the applicable
product reference safety information. For Ad26.ZEBOV and MVA-BN-Filo, the expectedness of
an adverse event will be determined by whether or not it is listed in the Investigator's Brochure.
For MenACWY, refer to the applicable vaccine prescribing information.
Adverse Event Associated With the Use of the Intervention
An adverse event is considered associated with the use of the intervention if the attribution is
related by the definitions listed in Section 12.1.2.

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An adverse event is considered not associated with the use of the intervention if the attribution is
unrelated by the definitions listed in Section 12.1.2.
12.1.2. 
Attribution Definitions
Every effort should be made by the investigator to explain any adverse event and to assess its
potential causal relationship, ie, to administration of the study intervention or to alternative causes
(eg, natural history of an underlying diseases, concomitant therapies). This applies to all adverse
events, whether serious or non-serious.
Causality of adverse events should be assessed by the investigator based on the following:
Related: there is suspicion that there is a relationship between study intervention and adverse event
(without determining the extent of that probability); there is a reasonable possibility that the study
intervention contributed to the adverse event. All adverse events assessed as possibly, probably or
definitely related to the study intervention will be considered related to the study intervention.
Unrelated: there is no suspicion that there is a relationship between the study intervention and the
adverse event; there are other more likely causes and administration of the study intervention is
not suspected to have contributed to the adverse event. All adverse event assessed as unrelated or
doubtfully related to the study intervention will be considered unrelated to the study intervention.
By definition, all solicited adverse events at the injection site (local) will be considered related to
the study intervention administration.
12.1.3. 
Severity Criteria
All adverse events, except for solicited adverse events, will be coded for severity using a modified
version of the Division of Microbiology and Infectious Diseases (DMID) pediatric grading table
(November 2007) (see Appendix 2)8.
For adverse events not identified in the table, the following guidelines will apply:
Mild  
Grade 1 
Symptoms causing no or minimal interference with usual
social and functional activities.
Moderate 
Grade 2 
Symptoms causing greater than minimal interference with
usual social and functional activities.
Severe 
Grade 3 
Symptoms causing inability to perform usual social and
functional activities.
Potentially Life- 
threatening 
Grade 4 
Any grade 3 symptom that requires hospitalization/in-
patient medical intervention.
Note: Only clinically significant abnormalities in laboratory data occurring from signing of the
ICF onwards will be reported as adverse events and graded using the table above.

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The investigator should use clinical judgment in assessing the severity of events not directly
experienced by the participant.
12.2. Special Reporting Situations
Safety events of interest on a sponsor study intervention that may require expedited reporting or
safety evaluation include, but are not limited to:
 
Overdose of a sponsor study intervention
 
Suspected abuse/misuse of a sponsor study intervention
 
Medication error involving a sponsor product (with or without participant exposure to
the sponsor study intervention, eg, name confusion)
Special reporting situations should be recorded in the CRF. Any special reporting situation that
meets the criteria of a serious adverse event should be recorded on the serious adverse event page
of the CRF.
12.3. Procedures
12.3.1. 
All Adverse Events
Symptoms of solicited local and systemic adverse events will be collected in the diary in the
evening after the first and second vaccination and then daily for the next 7 days. Unsolicited
adverse events will be reported from the first vaccination until 28 days post-dose-1, and from the
second vaccination until 28 days post-dose-2.
Serious adverse events and/or special reporting situations that are related to study procedures or
that are related to non-investigational (concomitant) sponsor products will be reported from the
time a signed and dated ICF is obtained onwards until the end of the study. All other serious
adverse events and/or special reporting situations will be reported from the day of the first
vaccination onwards until 6 months post-dose-2 in the main study and until 28 days post-dose-2
in the extension phase. The sponsor will evaluate any safety information that is spontaneously
reported by an investigator beyond the time frame specified in the protocol.
The investigator will monitor and analyze the study data including all adverse event and clinical
laboratory data as they become available and will make determinations regarding the severity of
the adverse experiences and their relation to study intervention. All adverse events will be deemed
related to study intervention or not related to study intervention, according to Section 12.1.2.
The investigator or clinical designee must review both post-injection reactogenicity and other
adverse event CRFs to insure the prompt and complete identification of all events that require
expedited reporting as serious adverse events, invoke pausing rules or are other serious and
unexpected events.
All adverse events, regardless of seriousness, severity, or presumed relationship to study
intervention, must be recorded using medical terminology in the source document and the CRF.
Whenever possible, diagnoses should be given when signs and symptoms are due to a common

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etiology (eg,cough, runny nose, sneezing, sore throat, and head congestion should be reported as
"upper respiratory infection"). Investigators must record in the CRF their opinion concerning the
relationship of the adverse event to study therapy. All measures required for adverse event
management must be recorded in the source document and reported according to sponsor
instructions.
The sponsor assumes responsibility for appropriate reporting of adverse events to the regulatory
authorities. The sponsor will also report to the investigator (and the head of the investigational
institute where required) all suspected unexpected serious adverse reactions (SUSARs). The
investigator (or sponsor where required) must report SUSARs to the appropriate IEC/IRB that
approved the protocol unless otherwise required and documented by the IEC/IRB. A SUSAR will
be reported to regulatory authorities unblinded. Participating investigators and IEC/IRB  will
receive a blinded SUSAR summary, unless otherwise specified.
The parent(s)/guardian will be provided with a "wallet (study) card" and instructed to carry this
card with their child 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 staff only)
 
Site number
 
Participant number
 
Any other information that is required to do an emergency breaking of the blind
 
Ebola prevention counseling
12.3.2. 
Serious Adverse Events
All serious adverse events occurring during the study must be reported to the appropriate sponsor
contact person by study-site personnel within 24hours of their knowledge of the event.
Information regarding serious adverse events will be transmitted to the sponsor using the Serious
Adverse Event Form, which must be completed and signed by a physician from the study site, and
transmitted to the sponsor within 24 hours. The initial and follow-up reports of a serious adverse
event should be made by facsimile (fax).
All serious adverse events that have not resolved by the end of the study, or that have not resolved
upon discontinuation of participation in the study, must be followed until any of the following
occurs:
 
The event resolves
 
The event stabilizes

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 
The event returns to baseline, if a baseline value/status is available
 
The event can be attributed to agents other than the study intervention 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 a serious
adverse event. Any event requiring hospitalization (or prolongation of hospitalization) that occurs
during the course of a subject's participation in a study must be reported as a serious adverse event,
except hospitalizations for the following:
 
Hospitalizations not intended to treat an acute illness or adverse event (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 serious adverse events. Any adverse event that results
in a prolongation of the originally planned hospitalization is to be reported as a new
serious adverse event.
During the entire study, the cause of death of a participant in a study, whether or not the event is
expected or associated with the study intervention, is considered a serious adverse event.
12.3.2.1. 
Thrombosis with Thrombocytopenia Syndrome
As described in Section 1.3.4, TTS has been observed very rarely following vaccination with
Janssen COVID-19 vaccine. TTS is a syndrome characterized by a combination of both a
thrombotic event and thrombocytopenia.2,5
Because this syndrome is rare and not completely understood, all cases of thrombosis and/or
thrombocytopenia will be considered a potential case of TTS and should be reported to the sponsor
within 24 hours of awareness as a serious adverse event. Each potential event will be reviewed to
identify a TTS case. A potential TTS case is defined as:
 
Thrombotic events: suspected deep vessel venous or arterial thrombotic events as detailed in
Appendix 3,
and/or
 
Thrombocytopenia, defined as platelet count below the lower limit of normal for the testing
lab.
Symptoms, signs, or conditions suggestive of a thrombotic event or thrombocytopenia should be
recorded and reported to Janssen  even if the final or definitive diagnosis has not yet been
determined, and alternative diagnoses have not yet been eliminated or shown to be less likely.
Follow-up information and final diagnoses, if applicable, should be submitted to the sponsor as
soon as they become available.

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In the event of thrombocytopenia, study site personnel should report the absolute value for the
platelet count and the reference range for the laboratory test used. Any potential events may require
enhanced data collection and evaluation. For example, Janssen may request that a platelet count
and/ a serum sample for advanced testing be obtained. Every effort should be made to report as
much information as possible about the event to Janssen in a reasonable timeframe.
If an event meets the criteria for a serious adverse event (Section 12.1.1), it should be reported
using the same process as for other serious adverse events.
Treatment and Follow-up Recommendation
The medical management of thrombotic events with thrombocytopenia is different from the
management of isolated thromboembolic diseases. Study site personnel and/or treating physicians
should follow available guidelines for treatment of thrombotic thrombocytopenia (eg, American
Society of Hematology 20212; British Society of Haematology 20216; CDC 20217). The use of
heparin may be harmful and alternative treatments may be needed. Consultation with a
hematologist is strongly recommended.
12.4. Contacting Sponsor Regarding Safety
The names (and corresponding telephone numbers) of the individuals who should be contacted
regarding safety issues or questions regarding the study are listed in the Contact Information
page(s), which will be provided as a separate document.
13. 
PRODUCT QUALITY COMPLAINT HANDLING
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, or reliability of a product, including its labeling or package integrity. A PQC may have
an impact on the safety and efficacy of the product. Timely, accurate, and complete reporting and
analysis of PQC information from studies are crucial for the protection of participants,
investigators, and the sponsor, and are mandated by regulatory agencies worldwide. The sponsor
has established procedures in conformity with regulatory requirements worldwide to ensure
appropriate reporting of PQC information; all studies conducted by the sponsor or its affiliates will
be conducted in accordance with those procedures.
13.1. 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.
If the defect is combined with a serious adverse event, the study-site personnel must report the
PQC to the sponsor according to the serious adverse event reporting timelines (refer to
Section 12.3.2). A sample of the suspected product should be maintained for further investigation
if requested by the sponsor.

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13.2. Contacting Sponsor Regarding Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted
regarding product quality issues are listed in the Contact Information page(s), which will be
provided as a separate document.
14. 
STUDY INTERVENTION INFORMATION
14.1. Physical Description of Study Intervention
14.1.1. 
Ad26.ZEBOV
Ad26.ZEBOV is a monovalent, replication-incompetent Ad26-based vector that expresses the full-
length EBOV Mayinga GP and is produced in the human cell line PER.C6®.
The Ad26.ZEBOV vaccine will be supplied at a concentration of 1x1011 vp/mL in 2-mL single-use
glass vials as a frozen liquid to be thawed before use. Each vial contains an extractable volume of
0.5 mL. Refer to the Investigator’s Brochure for a list of excipients.14
The Ad26.ZEBOV vaccine is manufactured by IDT Biologika GmbH for Janssen Vaccines &
Prevention B.V., The Netherlands.
14.1.2. 
MVA-BN-Filo
MVA-BN-Filo is a recombinant multivalent vaccine intended for active immunization against
Ebola and Marburg virus infection. MVA-BN-Filo is strongly attenuated; the vaccine is
propagated in primary chicken embryo fibroblast cells and does not replicate in human cells.
The MVA-BN-Filo vaccine is supplied at a concentration of 2 x 108 Inf U/mL in 2-mL single-use
glass vials as a frozen liquid suspension to be thawed before use. Each vial contains an extractable
volume of 0.5 mL. Refer to the Investigator’s Brochure for a list of excipients.14
The MVA-BN-Filo vaccine is manufactured by IDT Biologika GmbH for Janssen Vaccines &
Prevention B.V., The Netherlands.
14.1.3. 
MenACWY
MenACWY is a WHO-prequalified Meningococcal Group A, C, W135 and Y conjugate vaccine.
The MenACWY vaccines will be supplied as commercially available vaccines. Refer to the
Summary of Product Characteristics for a list of excipients.
14.2. Packaging
All study interventionwill be manufactured and packaged in accordance with Good Manufacturing
Practice (GMP). All study intervention will be packaged and labeled under the responsibility of
the sponsor. No study intervention can be repacked or relabeled without prior approval from the
sponsor.

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Further details for study intervention  packaging and labeling can be found in the Site
Investigational Product Procedures Manual.
14.3. Labeling
Study intervention labels will contain information to meet the applicable regulatory requirements.
14.4. Preparation, Handling, and Storage
All study intervention must be stored at controlled temperatures. Guidance on storage temperature
is provided in the Site Investigational Product Procedures Manual.
Vials must be stored in a secured location with no access for unauthorized personnel. All study
product storage equipment (includingrefrigerators,freezers) must be equipped with a continuous
temperature monitor and alarm, and with back-up power systems. In the event that study
intervention is exposed to temperatures outside the specified temperature ranges, all relevant data
will be sent to the sponsor to determine if the affected study intervention can be used or will be
replaced. The affected study intervention must be quarantined and not used until further instruction
from the sponsor is received.
A pharmacist/qualified staff member will prepare all doses for vaccine administration and provide
it for dispensing. In the main study, blinding will be achieved by preparation of study intervention
by unblinded qualified study-site personnel not involved in any other study-related procedures,
and by the administration of study intervention in a masked syringe in a way that maintains double-
blinding. In the extension phase, the preparation of the study intervention will be unblinded.
Full details on the preparation, the holding time and storage conditions from the time of preparation
to delivery of Ad26.ZEBOV  and MVA-BN-Filo and active control are provided in  the Site
Investigational Product Procedures Manual and Site Blinding Plan.
14.5. Intervention Accountability
The investigator is responsible for ensuring that all study intervention  received at the site is
inventoried and accounted for throughout the study. The study intervention administered to the
participant must be documented on the intervention accountability form. All study intervention
will be stored and disposed of according to the sponsor's instructions. Study-site personnel must
not combine contents of the study intervention containers.
Study intervention 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 intervention  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 intervention will be documented on the Investigational Product Destruction Form. When the
study site is an authorized destruction unit and study intervention supplies are destroyed on-site,
this must also be documented on the Investigational Product Destruction Form.

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Potentially hazardous materials such as used ampules, needles, syringes and vials containing
hazardous liquids, should be disposed of immediately in a safe manner and therefore will not be
retained for intervention accountability purposes.
Study intervention 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 intervention will be
supplied only to study participants. Returned study intervention must not be dispensed again, even
to the same participant. Study intervention may not be relabeled or reassigned for use by other
participants. The investigator agrees neither to dispense the study intervention from, nor store it
at, any site other than the study sites agreed upon with the sponsor.
15. 
STUDY-SPECIFIC MATERIALS
The investigator will be provided with the following supplies:
 
Investigator's Brochure and Addendum (if applicable) for Ad26.ZEBOV and MVA-
BN-Filo
 
Site Investigational Product Procedures Manual and Site Blinding Plan
 
Laboratory manual
 
IWRS Manual
 
Electronic Data Capture (eDC) Manual/electronic CRF Completion Guidelines
 
Sample ICF
 
Participant diaries
 
TOU
 
Rulers, thermometers
 
Participant wallet card
16. 
ETHICAL ASPECTS
16.1. Study-specific Design Considerations
Parent(s)/guardian of potential participants will be fully informed of the risks and requirements of
the study and, during the study, theywill be given any new information that may affect their decision
to continue participationof their child. They will be told that their consent for their child 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 parent(s)/guardian of participants
who are fully able to understand the risks, benefits, and potential adverse events of the study, and
provide their consent voluntarily will be allowed to enroll their child.
The primary ethical concern is the safety of the enrolled infants.
When referring to the signing of the ICF, the terms guardian and legally acceptable representative
refer to the legally appointed guardian of the child with authority to authorize participation in

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research. For each participant, his or her parent(s) (preferably both parents, if available) or legally
acceptable representative(s), as required by local regulations, must give written consent (permission)
according to local requirements after the nature of the study has been fully explained and before the
performance of any study-related assessments. For the purposes of this study, all references to
participants who have provided consent refers to the participant and his or her parent(s) or the
participant’s guardian(s) or legally acceptable representative(s) who have provided consent
according to this process.
The results of the study may be made available to the parent(s)/guardian of the participant at the
conclusion of the study according to local standards/restrictions.
Test of Understanding
The TOU (see Appendix 1) is a short assessment of the parent(s)/guardian of the potential
participant’s understanding of key aspects of the study. The test will help the study staff to
determine how well the parent(s)/guardian understand the study and their requirements for
participation of their child.
The parent(s)/guardian must pass the TOU, indicating that he or she understands the purpose of,
and procedures required for the study, after reading the informed consent and after the investigator
or designee has provided detailed information on the study and has answered the questions of the
parent(s)/guardian. The parent(s)/guardian must subsequently sign the ICF, indicating that he or
she is willing to allow their child to participate in the study.
Parent(s)/guardians are allowed to retake the test twice to achieve the passing score (≥90%)
required for participation of their child in the study. If a parent/guardian fails to achieve the passing
score, further information and counseling will be provided by the study team member.
Any parent/guardian of a potential participant not capable of understanding the key aspects of the
study, and their requirements for participation, should not be allowed to enroll their child.
Blood volume
The total blood volume to be collected in the main study is expected to be 8.0-9.5 mL, and 2 mL in
the extension phase. Details are provided in the Time and Events Schedule. The study-related blood
volumes obtained (including any losses during phlebotomy) will not exceed 3% of the total blood
volume during a period of 4weeks and will not exceed 1% at any single time. The total volume of
blood is estimated at 80 to 90 mL/kg body weight; 3% is 2.4 mL blood per kg body weight.9 The
allowable blood volume calculations are based on the 10th percentile for growth charts for infants.21
16.2. Regulatory Ethics Compliance
16.2.1. 
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the
protocol, current ICH guidelines on Good Clinical Practice (GCP), and applicable regulatory and
country-specific requirements.

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Good Clinical Practice is an international ethical and scientific quality standard for designing,
conducting, recording, and reporting studies that involve the participation of human subjects.
Compliance with this standard provides public assurance that the rights, safety, and well-being of
study subjects are protected, consistent with the principles that originated in the Declaration of
Helsinki,and that the study data are credible.
16.2.2. 
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 subjects)
 
Investigator's Brochure (or equivalent information) and amendments/addenda
 
Sponsor-approved subject recruiting materials
 
Information on compensation  for study-related injuries or payment to subjects 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 subjects
 
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
subjects, data or study conduct, unless required locally), the ICF, applicable recruiting materials,
and subject 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 subjects, data or study conduct)
 
Revision(s) to ICF and any other written materials to be provided to subjects
 
If applicable, new or revised subject recruiting materials approved by the sponsor
 
Revisions to compensation for study-related injuries or payment to subjects for
participation in the study, if applicable
 
New edition(s) of the Investigator's Brochure and amendments/addenda
 
Summaries of the status of the studyat intervals stipulated in guidelines of the IEC/IRB
(at least annually)

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 
Reports of adverse events that are serious, unlisted/unexpected, and associated with
the study intervention
 
New information that may adversely affect the safety of the subjects or the conduct of
the study
 
Deviations from or changes to the protocol to eliminate immediate hazards to the
subjects
 
Report of deaths of subjects 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 subjects, 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.
16.2.3. 
Informed Consent
The parent(s)/guardian of a participant (in this section referred to as the legally acceptable
representative) must give written consent according to local requirements after the nature of the
study (main study and extension phase [if applicable]) 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 legally
acceptable representative can read and understand. The informed consent should be in accordance
with principles that originated in the Declaration of Helsinki, current ICH and GCP guidelines,
applicable regulatory requirements, and sponsor policy.
Before enrollment in the study, the investigator or an authorized member of the study-site
personnel must explain to the legally acceptable representative of potential participants the aims,
methods, reasonably anticipated benefits, and potential hazards of the study, and any discomfort
participation in the study may entail. The legally acceptable representative will be informed that
the participation of their child is voluntary and that they may withdraw consent to participate at
any time. 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
legally acceptable representative is authorizing such access, which includes permission to obtain
information about his or her survival status. It also denotes that the legally acceptable

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representative agrees to allow his or her study physician to recontact the participant for the purpose
of obtaining consent for additional safety evaluations.
The legally acceptable representative will be given sufficient time to read the ICF and the
opportunity to ask questions. After this explanation and before entry into the study, consent should
be appropriately recorded by means of the legally acceptable representative's personally dated
signature. After having obtained the consent, a copy of the ICF must be given to the subject.
If the legally acceptable representative is unable to read or write, an impartial witness should be
present for the entire informed consent process (which includes reading and explaining all written
information) and should personally date and sign the ICF  after the oral consent of the legally
acceptable representative is obtained.
16.2.4. 
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 subjects confidential.
The informed consent obtained from the legally acceptable representative includes explicit consent
for the processing of personal data of the participant and for the investigator/institution to allow
direct access to his or her original medical records (source data/documents) for study-related
monitoring, audit, IEC/IRB review, and regulatory inspection. This consent also addresses the
transfer of the data to other entities and to other countries.
The legally acceptable representative has the right to request through the investigator access to the
personal data of their child and the right to request rectification of any data that are not correct or
complete. 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.
Exploratory research is not conducted under standards appropriate for the return of data to subjects.
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 subjects 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.
16.2.5. 
Long-term Retention of Samples for Additional Future Research
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 Ad26.ZEBOV and MVA-BN-

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Filo, to understand EVD, to understand differential intervention  responders, and to develop
tests/assays related to Ad26.ZEBOV and MVA-BN-Filo and EVD. The research may begin at any
time during the study or the post-study storage period.
Parent(s)/guardian will be asked to consent voluntarily for their child’s blood samples to be stored
for other research studies that may be done after this study is completed. Participants for whom
such consent is not given, can participate in the immunogenicity assessments without having their
blood samples stored for future testing (see also Section 10.2). In such case, their blood samples
will be destroyed after all the immunogenicity tests have been concluded (as agreed by the
sponsor).
All samples, for which consent has been obtained and for which additional material is available
after study-specified testing is complete, will be stored for future testing. A PCR test may be
performed to test for presence of Ebola virus in the samples if samples need to be exported.
Applicable approvals will be sought before any such samples are used for analysis not specified in
the protocol or a protocol amendment approved by the IEC/IRB.
Stored samples will be coded throughout the sample storage and analysis process and will not be
labeled with personal identifiers. Parent(s)/guardian may withdraw consent for their child’s
samples to be stored for research.
17. 
ADMINISTRATIVE REQUIREMENTS
17.1. 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.
17.2. 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 subjects, in which case the amendment must be
promptly submitted to the IEC/IRB and relevant competent authority. Documentation of
amendment approval by the investigator and IEC/IRB must be provided to the sponsor. When the

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change(s) involves only logistic or administrative aspects of the study, the IEC/IRB (where
required) only needs to be notified.
During the course of the study, in situations where a departure from the protocol is unavoidable,
the investigator or other physician in attendance will contact the appropriate sponsor representative
listed in the Contact Information page(s), which will be provided as a separate document. Except
in emergency situations, this contact should be made before implementing any departure from the
protocol. In all cases, contact with the sponsor must be made as soon as possible to discuss the
situation and agree on an appropriate course of action. The data recorded in the CRF and source
documents will reflect any departure from the protocol, and the source documents will describe
this departure and the circumstances requiring it.
17.3. Regulatory Documentation
17.3.1. 
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities
in each respective country, if applicable. A study may not be initiated until all local regulatory
requirements are met.
17.3.2. 
Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study intervention
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, subject 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

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 
Any other documentation required by local regulations
The following documents must be provided to the sponsor before enrollment of the first
participant:
 
Completed investigator financial disclosure forms from all subinvestigators
 
Documentation of subinvestigator qualifications (eg,curriculum vitae)
 
Name and address of any local laboratory conducting tests for the study, and a dated
copy of current laboratory normal ranges for these tests, if applicable
 
Local laboratory documentation demonstrating competence and test reliability
(eg,accreditation/license), if applicable
17.4. Subject Identification, Enrollment, and Screening Logs
The investigator agrees to complete a subject identification and enrollment log to permit easy
identification of each subject during and after the study. This document will be reviewed by the
sponsor study-site contact for completeness.
The participant identification and enrollment log will be treated as confidential and will be filed
by the investigator in the study file. To ensure participant confidentiality, no copy will be made.
All reports and communications relating to the study will identify subjects by participant
identification and age at initial informed consent. In cases where the subject is not randomized into
the study, the date seen and age at initial informed consent will be used.
The investigator must also complete a participant screening log, which reports on all participants
who were seen to determine eligibility for inclusion in the main study  and separately for the
extension phase of the study.
17.5. Source Documentation
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:
subject 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 adverse events and follow-up of adverse events; concomitant medication;
intervention receipt/dispensing/return records; study intervention administration information; and
date of study completion and reason for early discontinuation of study intervention or withdrawal
from the study, if applicable.
The author of an entry in the source documents should be identifiable.
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).

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The participant’s diary used to collect information regarding solicited symptoms after vaccination
will be considered source data.
The following data will be recorded directly into the CRF and will be considered source data:
 
Race
 
Pulse/heart rate and respiratory rate
 
Body length and weight
 
Details of physical examination
17.6. Case Report Form Completion
Case report forms are prepared and provided by the sponsor for each subject in electronic format.
All CRF 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 CRF are accurate and correct.
The study data will be transcribed by study-site personnel from the source documents onto an
electronic CRF, if applicable. Study-specific data will be transmitted in a secure manner to the
sponsor.
Worksheets may be used for the capture of some data to facilitate completion of the CRF. Any
such worksheets will become part of the subject's source documents. Data must be entered into
CRF in English. The CRF must be completed as soon as possible after a subject visit and the forms
should be available for review at the next scheduled monitoring visit.
If necessary, queries will be generated in the eDC tool. If corrections to a CRF are needed after
the initial entry into the CRF, 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.
17.7. 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 will review 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

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designee, as appropriate. After upload of the data into the study database they will be verified for
accuracy and consistency with the data sources.
17.8. 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 subject, 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.
17.9. Monitoring
The sponsor will perform study site visits to monitor this study.
The sponsor will perform on-site monitoring visits as frequently as necessary. The monitor will
record dates of the visits in a study site visit log that will be kept at the study site. The first post-
initiation visit will be made as soon as possible after enrollment has begun. At these visits, the
monitor will compare the data entered into the CRF with the vaccination unit and/or clinic records
(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 CRF 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

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relevant study-site personnel will be available, the source documents will be accessible, and a
suitable environment will be provided for review of study-related documents. The monitor will
meet with the investigator on a regular basis during the study to provide feedback on the study
conduct.
In the main study, there will be independent monitoring of the pharmacy and preparation of study
intervention by an unblinded monitor (independent study intervention monitor); regular monitors
will be blinded. In the extension phase, the preparation of the study intervention will be unblinded.
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.
17.10. Study Completion/Termination
17.10.1. 
Study Completion/End of Study
The study is considered completed at final database lock,which will occur after the last participant
in the study has completed their last study-related visit, or left 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.
17.10.2. 
Study Termination
The sponsor reserves the right to close the study site or terminate the study at any time for any
reason at the sole discretion of the sponsor. Study sites will be closed upon study completion. A
studysite 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 termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are not
limited to:
 
Failure of the investigator to comply with the protocol, the requirements of the
IEC/IRB or local health authorities, the sponsor's procedures, or GCP guidelines
 
Inadequate recruitment of subjects by the investigator
 
Discontinuation of further study intervention development
17.11. 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. Subject privacy must, however, be respected.
The investigator and study-site personnel are responsible for being present and available for

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consultation during routinely scheduled study-site audit visits conducted by the sponsor or its
designees.
Similar auditing procedures may also be conducted by agents of any regulatory body, either as part
of a national GCP compliance program or to review the results of this study in support of a
regulatory submission. The investigator should immediately notify the sponsor if he or she has
been contacted by a regulatory agency concerning an upcoming inspection.
17.12. Use of Information and Publication
All information, including but not limited to information regarding Ad26.ZEBOV and MVA-BN-
Filo 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 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 Ad26.ZEBOV and MVA-BN-Filo, and
thus may be disclosed as required to other clinical investigators or regulatory agencies. To permit
the information derived from the clinical studies to be used, the investigator is obligated to provide
the sponsor with all data obtained in the study.
The results of the study will be reported in a Clinical Study Report generated by the sponsor and
will contain data from all study sites that participated in the study as per protocol. Recruitment
performance or specific expertise related to the nature and the key assessment parameters of the
study will be used to determine a coordinating investigator for the study. Results of exploratory
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 subject identifiers will
not be used in publication of results. Any work created in connection with performance of the
study and contained in the data that can benefit from copyright protection (except any publication
by the investigator as provided for below) shall be the property of the sponsor as author and owner
of copyright in such work.
Consistent with Good Publication Practices and International Committee of Medical Journal
Editors 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

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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 substudy 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 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
ofthe work; or the acquisition, analysis, or interpretation of the data for the work; and drafted the
work or revised it critically for important intellectual content; and given final approval of the
version to be published; and agreed to be accountable for all aspects of the work in ensuring that
questions related to the accuracy or integrity of any part of the work are appropriately investigated
and resolved.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and disclose the existence of and the results of clinical studies as required
by law.

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18. 
COVID-19 APPENDIX: GUIDANCE ON STUDY CONDUCT DURING THE
COVID-19 PANDEMIC
It is recognized that the Coronavirus Disease 2019 (COVID-19) pandemic may have an impact on
the conduct of this clinical study due to, for example, self-isolation/quarantine by participants and
study-site personnel; travel restrictions/limited access to public places, including hospitals; study
site personnel being reassigned to critical tasks.
In alignment with recent health authority guidance, the sponsor is providing options for study
related participant management in the event of disruption to the conduct of the study. This guidance
does not supersede any local or government requirements or the clinical judgement of the
investigator to protect the health and well-being of participants and site staff. If, at any time, a
participant’s safety is considered to be at risk, study intervention will be discontinued, and study
follow-up will be conducted.
Scheduled visits that cannot be conducted in person at the study site will be performed to the extent
possible remotely/virtually or delayed until such time that on-site visits can be resumed. At each
contact, participants will be interviewed to collect safety data. Key efficacy endpoint assessments
should be performed if required and as feasible. Participants will also be questioned regarding
general health status to fulfill any physical examination requirement.
Every effort should be made to adhere to protocol-specified assessments for participants on study
intervention, including follow up. Modifications to protocol-required assessments may be
permitted via COVID-19 Appendix after consultation with the participant, investigator, and the
sponsor. Missed assessments/visits will be captured in the clinical trial management system for
protocol deviations. Discontinuations of study interventions and withdrawal from the study should
be documented with the prefix “COVID-19-related” in the case report form (CRF).
The sponsor will continue to monitor the conduct and progress of the clinical study, and any
changes will be communicated to the sites and to the health authorities according to local guidance. 
If a participant has tested positive for COVID 19, the investigator should contact the sponsor’s
responsible medical officer to discuss plans for study intervention and follow-up. Modifications
made to the study conduct as a result of the COVID-19 pandemic should be summarized in the
clinical study report.

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REFERENCES
1. 
Agua-Agum J, Ariyarajah A, Blake IM, et al. (for the WHO Ebola Response Team) Ebola virus disease among
children in West Africa. N Engl J Med. 2015;372(13):1274-1277.
2. 
American Society of Hematology. COVID-19 resources. Thrombosis with Thrombocytopenia Syndrome (also
termed Vaccine-induced Thrombotic Thrombocytopenia). https://www.hematology.org/covid-19/vaccine-
induced-immune-thrombotic-thrombocytopenia. Accessed: 12 May 2021.
3. 
Baize S, Pannetier D, Oestereich L, et al. Emergence of Zaire Ebola virus disease in Guinea. N Engl J Med.
2014;371(15):1418-1425.
4. 
Bonhoeffer J (2004), Menkes J, Gold MS, et al. Generalized convulsive seizure as an adverse event following
immunization: case definition and guidelines for data collection, analysis, and presentation Vaccine
2004;22:557-562.
5. 
Brighton Collaboration. Interim Case Definition of Thrombosis with Thrombocytopenia Syndrome (TTS). 21
April 2021. https://brightoncollaboration.us/thrombosis-with-thrombocytopenia-syndrome-interim-case-
definition/. Accessed: 12 May 2021.
6. 
British Society for Haematology. Guidance produced from the Expert Haematology Panel (EHP) focussed on
Covid-19 Vaccine induced Thrombosis and Thrombocytopenia (VITT). https://b-s-
h.org.uk/media/19530/guidance-version-13-on-mngmt-of-thrombosis-with-thrombocytopenia-occurring-after-
c-19-vaccine 20210407.pdf. Version 1.3; 7 April 2021.  Accessed: 12 May 2021.
7. 
Centers for Disease Control and Prevention (CDC). Cases of cerebral venous sinus thrombosis with
thrombocytopenia after receipt of the Johnson & Johnson COVID-19 Vaccine. 13 April 2021.
https://emergency.cdc.gov/han/2021/han00442.asp. Accessed: 12 May 2021.
8. 
Division of Microbiology and Infectious Diseases (DMID) Pediatric Toxicity Tables November 2007 Draft.
Available from: https://www.niaid.nih.gov/sites/default/files/dmidpedtox.pdf. Accessed October 2018.
9. 
Ethical Considerations for Clinical Trials on Medicinal Products Conducted With the Pediatric Population:
Recommendations of the Ad Hoc Group for the Development of Implementing Guidelines for Directive
2001/20/EC Relating to Good Clinical Practice in the Conduct of Clinical Trials on Medicinal Products for
Human Use. 2008.
10. Friedrich B, Trefry J, Biggins J, et al. Potential vaccines and post-exposure treatments for filovirus infections.
Viruses. 2012;4(9):1619-1650.
11. Gidudu JK, Walco GA, Taddio A, et al./The Brighton Immunization Site Pain Working Group. Immunization
site pain: Case definition and guidelines for collection, analysis, and presentation of immunization safety data.
Vaccine. 2012:30;4558-4577.
12. Investigator’s Brochure: JNJ-61210474 (Ad26.ZEBOV) Edition 5. Janssen Vaccines & Prevention
(October 2017).
13. Investigator’s Brochure: MVA-BN-Filo (MVA-mBN226B) Edition 11. Bavarian Nordic A/S (June 2017).
14. Investigator’s Brochure: VAC52150 (Ad26.ZEBOV, MVA-BN-Filo [MVAmBN226B]) Edition 1. Janssen
Vaccines & Prevention (December 2020).
15. Investigator’s Brochure: VAC52150 (Ad26.ZEBOV, MVA-BN-Filo [MVAmBN226B]) Edition 1,
Addendum 1. Janssen Vaccines & Prevention (April 2021).
16. Investigator’s Brochure: VAC52150 (Ad26.ZEBOV, MVA-BN-Filo [MVAmBN226B]) Edition 1,
Addendum 2. Janssen Vaccines & Prevention (May 2021).
17. Khair AM (2015), Elmagrabi D. Febrile Seizures and Febrile Seizure Syndromes: An Updated Overview of
Old and Current Knowledge. Neur. Res. Int. 2015; Article ID 849341. https://doi.org/10.1155/2015/849341.
18. Kohl KS, Walop W, Gidudu J, et al./The Brighton Collaboration Local Reaction Working Group for Swelling
at or near Injection Site. Swelling at or near injection site: Case definition and guidelines for collection,
analysis and presentation of immunization safety data. Vaccine 2007:31;5858-5874.

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19. Marcy SM, Kohl KS, Dagan R, et al./The Brighton Collaboration Fever Working Group. Fever as an adverse
event following immunization: case definition and guidelines of data collection, analysis, and presentation.
Vaccine 2004:22;551-556.
20. Smit MA, Michelow IC, Glavis-Bloom J, Wolfman V, Levine AC. Characteristics and outcomes of pediatric
patients with Ebola virus disease admitted to treatment units in Liberia and Sierra Leone: a retrospective cohort
study. Clin Infect Dis. 2017;64(3):243-249.
21. WHO Child Growth Standards. Available at: http://www.who.int/childgrowth/standards/weight for age/en/.
Accessed October 2018.
22. WHO Fact Sheet No103 Ebola Virus Disease 2014. Available at:
http://www.who.int/mediacentre/factsheets/fs103/en/. Accessed October 2018.
23. WHO Global Health Observatory data –meningitis 2010. Available at:
http://www.who.int/gho/epidemic diseases/meningitis/suspected cases deaths text/en/. Accessed October
2018.
24. WHO Health Statistics and Information Systems: Disease and Injury Country Estimates. Available at:
http://www.who.int/healthinfo/global burden disease/estimates country/en/. Accessed October 2018.

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Appendix 2: Toxicity Grading Scale for Healthy Pediatric Participants up to 3 Years of Age Enrolled in
Preventive Vaccine Clinical Trials
Adapted from: Division of Microbiology and Infectious Diseases (DMID° Pediatric Toxicity Tables (November
2007, draft). For adverse events not included in the tables below, refer to the severity criteria guidelines in
Section 12.1.3. Local lab references take preference over the DMD table and the different grades.
The abbreviations used in the following tables are: LLN: lower limit of normal; IV: intravenous; ULN: upper limit
of normal.
LOCAL REACTIONS
Grade 1 
Grade 2 
Grade 3 
Grade 4
Tenderness 
Mild discomfort to 
touch; minimal to no 
limitation of use of 
limb 
Notable discomfort 
to touch; Greater 
than minimal 
limitation of use of 
limb
Significant 
discomfort at rest; 
Severe limitation of
use of limb
Hospitalization or ER
visit for treatment
Erythema 
<10mm 
1025mm 
26 50 mm  
>50 mm or any
grade 3 with
hospitalization or ER
visit for treatment
Swelling 
<10mm 
1025 mm  
26 50 mm  
>50 mm or any
grade 3 with
hospitalization or ER
visit for treatment
HEMATOLOGY
Grade 1 
Grade 2 
Grade 3 
Grade 4
Hemoglobin for children 
greater than 3 months and 
less than 2 years of age 
9.0-9.9 gm/dL 
7.0-8.9 gm/dL 
<7.0 gm/dL 
Cardiac Failure
secondary to
Anemia
Hemoglobin for children 
greater than 2 years of age 
10.010.9 gm/dL 
7.09.9 gm/dL 
<7.0 gm/dL 
Cardiac Failure
secondary to
Anemia
Absolute Neutrophil Count 
750-1200/mm3 
400-749/mm3 
250-399/mm3 
<250/mm3
Platelets 
75,00099,999/mm3 
50,00074,999/mm3 
25,00049,999/mm3 
<25,000/mm3
Prothrombin Time (PT) 
1.1 1.2 x ULN  
1.3 1.5 x ULN  
1.6 3.0 x ULN  
>3.0 x ULN
Partial Thromboplastin Time 
(PTT)
1.1 1.6 x ULN  
1.7 2.3 x ULN  
2.4 3.0 x ULN  
>3.0x ULN

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GASTROINTESTINAL
Grade 1 
Grade 2 
Grade 3 
Grade 4
Bilirubin (Fractionated bilirubin test must be performed when total bilirubin is elevated)
Bilirubin for children greater
than 3 months of age (when
accompanied by any
increase in other liver
function test)
1.1 <1.25 x ULN  
1.25 <1.5 x ULN  
1.51.75 x ULN  
>1.75 x ULN  
Bilirubin for children greater 
than 3 months of age (when
other liver functions are in
the normal range)
1.1 <1.5 x ULN  
1.5 <2.0 x ULN  
2.03.0 x ULN  
>3.0x ULN
AST (SGOT) 
1.1 <2.0 x ULN  
2.0 <3.0 x ULN  
3.08.0 x ULN  
>8.0 x ULN
ALT (SGPT) 
1.1 <2.0 x ULN  
2.0 <3.0 x ULN  
3.08.0 x ULN  
>8.0 x ULN
GGT 
1.1 <2.0 x ULN  
2.0 <3.0 x ULN  
3.08.0 x ULN  
>8.0 x ULN
Pancreatic Amylase 
1.1 1.4 x ULN  
1.5 1.9 x ULN  
2.03.0 x ULN  
>3.0 x ULN
Uric Acid 
7.59.9 mg/dL 
10.012.4 mg/dL 
12.515.0 mg/dL 
>15.0 mg/dL
Loss of Appetite 
Feeding minimally 
reduced 
Feeding reduced by 
more than 50% of 
normal for the child 
Refusing all feeds 
No solid or liquid
taken orally for in
the last 24 hours;
requires intravenous
fluids
Diarrhea 
Change in 
consistency of stools 
OR increase of 1 3 
stools over baseline 
per 24 hour period 
liquid/watery stools 
OR increase of 4 to 6 
stools over baseline 
per 24 hour period 
Increase of ≥7 stools 
over baseline per 
24 hour period 
Requires IV fluid
resuscitation and
electrolytes
repletion OR
hypotensive shock
Constipation
Slight change in
consistency and/or
frequency of stools
Hard, dry stools with
a change in
frequency
Intestinal
obstruction
accompanied with
abdominal pain
Hospitalization;
Severe abdominal
distention and
vomiting accompani
ed with severe
abdominal pain
Vomiting 
1 episode/ day (24h) 
2 3 episodes per day
(24h)
4 6 episodes per day
(24h)
Greater than
6 episodes per day
(24h) OR intractable
vomiting

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ELECTROLYTES
Grade 1 
Grade 2 
Grade 3 
Grade 4
Creatinine
3 Months –2 Years of age 
0.6 0.8 x ULN  
0.9 1.1 x ULN  
1.2 1.5 x ULN  
> 1.5 x ULN
2 Years –3 Years of age 
0.7 1.0 x ULN  
1.1 1.6 x ULN  
1.7 2.0 x ULN  
>2.0 x ULN
Hypernatremia 
 
145149 mEq/L 
150155 mEq/L 
>155 mEq/L or
abnormal sodium
AND mental status
changes
Hyponatremia 
 
130135 mEq/L 
129 124 mEq/L 
<124 mEq/L or
abnormal sodium
AND mental status
changes
Hyperkalemia 
5.05.9 mEq/L 
6.06.4 mEq/L 
6.57.0 mEq/L 
>7.0 mEq/L or
abnormal potassium
AND cardiac
arrhythmia
Hypokalemia 
3.03.5 mEq/L 
2.52.9 mEq/L 
2.02.4 mEq/L 
<2.0 mEq/L or
abnormal potassium
AND cardiac
arrhythmia
Hypercalcemia 
10.511.2 mg/dL 
11.3 11.9 mg/dL 
12.012.9 mg/dL 
>13.0 mg/dL
Hypocalcemia 
7.8 8.4 mg/dL 
7.07.7 mg/dL 
6.06.9 mg/dL 
>6.0 mg/dL
Hypomagnesemia 
1.2 1.4 mEq/L 
0.9 1.1 mEq/L 
0.6 0.8 mEq/L 
<0.6 mEq/L or
abnormal
magnesium AND
cardiac arrhythmia
hypoglycemia 
5565 mg/dL 
4054 mg/dL 
3039 mg/dL 
<30 mg/dL or
adnormal glucose
AND mental status
changes
Hyperglycemia 
116 159 mg/dL 
160249 mg/dL 
250400 mg/dL 
>400 mg/dL or
ketoacidosis
Proteinuria 
Tr 1+ or <150 
mg/day 
2+ or 150499 
mg/day 
3+ or 5001000 
mg/day 
4+ or Nephrotic
syndrome >1000
mg/day
Hematuria 
Microscopic <25 
cells/hpf 
Microscopic >25 
cells/hpf 
Gross hematuria 
Hospitalization; Life
threatening
consequences

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Neurologic
Grade 1 
Grade 2 
Grade 3 
Grade 4
Irritability 
Easily consolable;
minimal or no
interference with
activity. Episodes of
continuous crying
<60 min.
Difficult to console.
Episodes of
continuous crying
>60 min <120 min
Inconsolable,
prevents daily
activity.
Episodes of
continuous crying
>120 min
Hospitalization or ER
visit for treatment
Decreased Activity 
Minimal decrease in
alertness, minimal
or no interference
with activity
Some interference
with activity, slightly
subdued
unable to achieve
normal level of
alertness, lethargic
ER visit or
hospitalization for
treatment or life
threatening
consequences
Neuropathy/ Lower Motor
Neuropathy
 
Mild transient
Paresthesia only
Persistent or
progressive
paresthesia, burning
sensation in feet, or
mild dysesthesia; no
weakness; mild to
moderate deep
tendon reflex
changes; no sensory
loss
Onset of significant
weakness, decrease
or loss of DTRs,
sensory loss in
"stocking glove"
distribution,
radicular sensory
loss, multiple cranial
nerve involvement;
bladder or bowel
dysfunction,
fasciculations,
respiratory
embarrassment
from chest wall
weakness.
Myopathy or
Neuromuscular Junction
Impairment
Normal or mild (<2 x
ULN) CPK elevation
Mild proximal
weakness and/or
atrophy not
affecting gross
motor function. Mild
myalgias, +/ mild
CPK elevation (<2 x
ULN)
Proximal muscle
weakness and/or
atrophy affecting
motor function +/
CPK elevation; or
severe myalgias with
CPK >2 x ULN;
Onset of
myasthenia like
symptoms (fatigable
weakness with
external, variable
ophthalmoplegia
and/or ptosis), or
neuromuscular
junction blockade
(acute paralysis)
symptoms
OTHER
Grade 1 
Grade 2 
Grade 3 
Grade 4
Fever/pyrexia 
38.0 38.4 °C or 
100.4 101.1 °F 
38.5 38.9 °C or 
101.2 102.0 °F 
39.0 40.0 °C or 
102.1 104.0 °F 
Greater than 40 °C
or 104.0 °F
Acute allergic reaction 
Pruritus without 
Rash 
Pruritic Rash 
Mild Urticaria 
Severe Urticaria
Anaphylaxis,
Angioedema
Stomatitis 
Mild discomfort 
Painful, difficulty 
swallowing, but able 
to eat and drink 
Painful: unable to 
swallow solids 
Painful: unable to
swallow liquids;
requires IV fluids
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

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Appendix 3: Thrombotic Events to be Reported
At the time of protocol amendment 4writing, the list of thrombotic events to be reported to the
sponsor as potential TTS is provided below. Further guidance may become available on thrombotic
events of interest.
 
MedDRA PTs for large vessel thrombosis and embolism
 
Aortic embolus, aortic thrombosis, aseptic cavernous sinus thrombosis, brain stem
embolism, brain stem thrombosis, carotid arterial embolus, carotid artery thrombosis,
cavernous sinus thrombosis, cerebral artery thrombosis, cerebral venous sinus
thrombosis, cerebral venous thrombosis, superior sagittal sinus thrombosis, transverse
sinus thrombosis, mesenteric artery embolism, mesenteric artery thrombosis, mesenteric
vein thrombosis, splenic artery thrombosis, splenic embolism, splenic thrombosis,
thrombosis mesenteric vessel, visceral venous thrombosis, hepatic artery embolism,
hepatic artery thrombosis, hepatic vein embolism, hepatic vein thrombosis, portal vein
embolism, portal vein thrombosis, portosplenomesenteric venous thrombosis, splenic
vein thrombosis, spontaneous heparin-induced thrombocytopenia syndrome, femoral
artery embolism, iliac artery embolism, jugular vein embolism, jugular vein thrombosis,
subclavian artery embolism, subclavian vein thrombosis, obstetrical pulmonary
embolism, pulmonary artery thrombosis, pulmonary thrombosis, pulmonary venous
thrombosis, renal artery thrombosis, renal embolism, renal vein embolism, renal vein
thrombosis, brachiocephalic vein thrombosis, vena cava embolism, vena cava
thrombosis, truncus coeliacus thrombosis
 
MedDRA PTs for more common thrombotic events
 
Axillary vein thrombosis, deep vein thrombosis, pulmonary embolism, MedDRA PTs for
acute myocardial infarction*, MedDRA PTs for stroke*
Source: Shimabukuro T. CDC COVID-19 Vaccine Task Force. Thrombosis with thrombocytopenia syndrome (TTS)
following Janssen COVID-19 vaccine. Advisory Committee on Immunization Practices (ACIP). April 23, 2021.
https://www.cdc.gov/vaccines/acip/meetings/slides-2021-04-23.html.
*Vaccine Adverse Event Reporting System (VAERS) Standard Operating Procedures for COVID-19 (as of 29 January
2021) https://www.cdc.gov/vaccinesafety/pdf/VAERS-v2-SOP.pdf

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INVESTIGATOR AGREEMENT
I have read this protocol and agree that it contains all necessary details for carrying out this study. I will
conduct the study as outlined herein and will complete the study within the time designated.
I will provide copies of the protocol and all pertinent information to all individuals responsible to me who
assist in the conduct of this study. I will discuss this material with them to ensure that they are fully informed
regarding the study drug, 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

Signature
User 
Date 
Reason
 
30-Sep-2021 
12:04:18
(GMT)
Document Approval
PPD