A Staged Phase 3 Study, Including a Double-Blinded Controlled Stage to Evaluate the Safety and Immunogenicity of Ad26.ZEBOV and MVA-BN-Filo as Candidate Prophylactic Vaccines for Ebola
Phase: PHASE3
Conditions: Ebola Virus Disease
Sponsor: Janssen Vaccines & Prevention B.V.

1
Status: Approved, Date: 2 October 2018
Janssen Vaccines & Prevention B.V.* #
Clinical Protocol
A Staged Phase 3 Study, Including a Double-Blinded Controlled Stage to Evaluate the 
Safety and Immunogenicity of Ad26.ZEBOV and MVA-BN-Filo as Candidate Prophylactic 
Vaccines for Ebola
Protocol VAC52150EBL3001; Phase 3
AMENDMENT 7
EBOVAC – Salone
London School of Hygiene & Tropical Medicine#
Ministry of Health and Sanitation of Sierra Leone (MoHS)
College of Medicine and Allied Health Sciences (COMAHS)
Ebola Vaccine Deployment, Acceptance & Compliance (EBODAC) Program
Innovative Medicines Initiative (IMI)-1
VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
*Janssen Vaccines & Prevention B.V. (formerly known as Crucell Holland 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.
# EBOVAC1 Consortium Partners. Other Consortium Partners are: Institut National de la Santé et de la 
Recherche Médicale and Oxford University
.
Status:
Approved  
Date:
2 October 2018
EDMS number:
EDMS-ERI-123324264, 10.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements. 
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and 
may not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed 
by them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as 
privileged or confidential.
NCT02509494

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Approved, Date: 2 October 2018
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF ATTACHMENTS............................................................................................................................ 5
LIST OF IN-TEXT TABLES.......................................................................................................................... 5
PROTOCOL AMENDMENTS....................................................................................................................... 6
SYNOPSIS.................................................................................................................................................. 27
TIME AND EVENTS SCHEDULES ............................................................................................................ 34
TIME AND EVENTS SCHEDULE – STAGE 1........................................................................................... 34
TIME AND EVENTS SCHEDULE – STAGE 1 CONTINUED (THIRD VACCINATION)............................ 37
TIME AND EVENTS SCHEDULE – STAGE 2........................................................................................... 39
ABBREVIATIONS ...................................................................................................................................... 42
DEFINITIONS OF TERMS.......................................................................................................................... 43
1.
INTRODUCTION................................................................................................................................ 44
1.1.
Background .................................................................................................................................... 44
1.2.
Risk Benefit Section....................................................................................................................... 50
1.2.1.
Known Benefits........................................................................................................................... 50
1.2.2.
Potential Benefits........................................................................................................................ 50
1.2.3.
Known Risks............................................................................................................................... 50
1.2.4.
Potential Risks............................................................................................................................ 51
1.2.5.
Unknown Risks........................................................................................................................... 53
1.2.6.
Overall Benefit/Risk Assessment ............................................................................................... 53
1.3.
Overall Rationale for the Study...................................................................................................... 54
2.
OBJECTIVES AND HYPOTHESIS ................................................................................................... 55
2.1.
Objectives ...................................................................................................................................... 55
2.2.
Hypothesis ..................................................................................................................................... 56
3.
STUDY DESIGN AND RATIONALE ................................................................................................. 56
3.1.
Overview of Study Design.............................................................................................................. 56
3.2.
Study Design Rationale.................................................................................................................. 58
4.
SUBJECT POPULATION.................................................................................................................. 59
4.1.
Inclusion Criteria ............................................................................................................................ 60
4.2.
Exclusion Criteria ........................................................................................................................... 62
4.3.
Prohibitions and Restrictions ......................................................................................................... 64
5.
TREATMENT ALLOCATION AND BLINDING................................................................................. 65
6.
DOSAGE AND ADMINISTRATION .................................................................................................. 68
7.
TREATMENT COMPLIANCE............................................................................................................ 70
8.
PRESTUDY AND CONCOMITANT THERAPY ................................................................................ 70
9.
STUDY EVALUATIONS .................................................................................................................... 71
9.1.
Study Procedures........................................................................................................................... 71
9.1.1.
Overview..................................................................................................................................... 71

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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9.1.2.
Screening Phase ........................................................................................................................ 72
9.1.3.
Vaccination Period...................................................................................................................... 73
9.1.4.
Post-Boost and Post-Third Vaccination Period .......................................................................... 75
9.1.5.
Long-Term Follow-Up................................................................................................................. 75
9.1.6.
Evaluation of Fever..................................................................................................................... 76
9.1.7.
Early Withdrawal......................................................................................................................... 77
9.2.
Immunogenicity.............................................................................................................................. 77
9.2.1.
Endpoints.................................................................................................................................... 77
9.2.2.
Evaluations ................................................................................................................................. 77
9.3.
Safety ............................................................................................................................................. 78
9.3.1.
Endpoints.................................................................................................................................... 78
9.3.2.
Evaluations ................................................................................................................................. 78
9.4.
Sample Collection and Handling.................................................................................................... 82
10.
SUBJECT COMPLETION/WITHDRAWAL....................................................................................... 83
10.1.
Completion ..................................................................................................................................... 83
10.2.
Discontinuation of Study Vaccine .................................................................................................. 83
10.3.
Contraindications to Vaccination.................................................................................................... 84
10.4.
Withdrawal From the Study............................................................................................................ 84
11.
STATISTICAL METHODS................................................................................................................. 85
11.1.
Analysis Sets.................................................................................................................................. 86
11.2.
Subject Information ........................................................................................................................ 86
11.3.
Sample Size Determination ........................................................................................................... 87
11.4.
Immunogenicity Analyses .............................................................................................................. 88
11.5.
Safety Analyses ............................................................................................................................. 88
11.6.
Interim Analysis.............................................................................................................................. 89
11.7.
Independent Data Monitoring Committee (IDMC) ......................................................................... 89
11.7.1.
Safety.......................................................................................................................................... 90
11.8.
Clinical Steering Committee and Management Committee........................................................... 90
11.9.
Pausing Rules ................................................................................................................................ 90
11.9.1.
Stage 1........................................................................................................................................ 91
11.9.2.
Stage 2........................................................................................................................................ 91
11.9.2.1.
Adults and Adolescents (Aged ≥12 Years).............................................................................. 91
11.9.2.2.
Children (Aged ≥1 to 11 Years, Inclusive)............................................................................... 92
12.
ADVERSE EVENT REPORTING ...................................................................................................... 92
12.1.
Definitions ...................................................................................................................................... 92
12.1.1.
Adverse Event Definitions and Classifications ........................................................................... 92
12.1.2.
Attribution Definitions.................................................................................................................. 94
12.1.3.
Severity Criteria .......................................................................................................................... 95
12.2.
Special Reporting Situations.......................................................................................................... 96
12.3.
Procedures..................................................................................................................................... 96
12.3.1.
All Adverse Events...................................................................................................................... 96
12.3.2.
Serious Adverse Events ............................................................................................................. 97
12.3.3.
Immediate Reportable Events .................................................................................................... 98
12.3.4.
Pregnancy................................................................................................................................... 99
12.4.
Contacting Sponsor Regarding Safety........................................................................................... 99
13.
PRODUCT QUALITY COMPLAINT HANDLING.............................................................................. 99
13.1.
Procedures..................................................................................................................................... 99
13.2.
Contacting Sponsor Regarding Product Quality .......................................................................... 100
14.
STUDY VACCINE INFORMATION ................................................................................................. 100
14.1.
Description of Study Vaccines ..................................................................................................... 100
14.1.1.
Ad26.ZEBOV ............................................................................................................................ 100
14.1.2.
MVA-BN-Filo............................................................................................................................. 100
14.1.3.
MenACWY................................................................................................................................ 100

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Approved, Date: 2 October 2018
14.1.4.
Placebo..................................................................................................................................... 101
14.2.
Packaging and Labeling............................................................................................................... 101
14.3.
Preparation, Handling and Storage.............................................................................................. 101
14.4.
Vaccine Accountability ................................................................................................................. 101
15.
STUDY-SPECIFIC MATERIALS..................................................................................................... 102
16.
ETHICAL ASPECTS ....................................................................................................................... 102
16.1.
Study-Specific Design Considerations......................................................................................... 102
16.2.
Regulatory Ethics Compliance..................................................................................................... 104
16.2.1.
Investigator Responsibilities ..................................................................................................... 104
16.2.2.
Independent Ethics Committee or Institutional Review Board ................................................. 104
16.2.3.
Informed Consent ..................................................................................................................... 105
16.2.4.
Privacy of Personal Data .......................................................................................................... 107
16.2.5.
Long-Term Retention of Samples for Additional Future Research .......................................... 107
17.
ADMINISTRATIVE REQUIREMENTS ............................................................................................ 108
17.1.
Protocol Amendments.................................................................................................................. 108
17.2.
Regulatory Documentation .......................................................................................................... 108
17.2.1.
Regulatory Approval/Notification .............................................................................................. 108
17.2.2.
Required Prestudy Documentation........................................................................................... 108
17.3.
Subject Identification, Enrollment, and Screening Logs .............................................................. 109
17.4.
Source Documentation................................................................................................................. 110
17.5.
Case Report Form Completion .................................................................................................... 110
17.6.
Data Quality Assurance/Quality Control ...................................................................................... 111
17.7.
Record Retention ......................................................................................................................... 111
17.8.
Monitoring .................................................................................................................................... 112
17.9.
Study Completion/Termination..................................................................................................... 112
17.9.1.
Study Completion ..................................................................................................................... 112
17.9.2.
Study Termination..................................................................................................................... 113
17.10.
On-Site Audits .............................................................................................................................. 113
17.11.
Use of Information and Publication.............................................................................................. 113
REFERENCES.......................................................................................................................................... 115
ATTACHMENTS....................................................................................................................................... 116
INVESTIGATOR AGREEMENT ............................................................................................................... 130
LAST PAGE.............................................................................................................................................. 130

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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LIST OF ATTACHMENTS
Attachment 1:
Schematic Presentation of the IDMC Schedule for the Prime and Boost 
Vaccination ................................................................................................................... 116
Attachment 2:
Test of Understanding (TOU) ....................................................................................... 117
Attachment 3:
Fever Management Algorithm ...................................................................................... 118
Attachment 4: 
Toxicity Tables for Use in Trials Enrolling Healthy Adults and Adolescents ................ 119
Attachment 5: 
Toxicity Tables for Use in Trials Enrolling Children Greater Than 3 Months of 
Age................................................................................................................................ 125
LIST OF IN-TEXT TABLES
Table 1:
Number of Subjects Planned per Stage and Population for Safety   and 
Immunogenicity Assessments ........................................................................................ 32
Table 2: 
Study Vaccination Schedules ......................................................................................... 69
Table 3:
Summary of Potential Immunologic Assays (Serology).................................................. 78
Table 4:
Number of Subjects Planned per Stage and Population for Safety   and 
Immunogenicity Assessments ........................................................................................ 87
Table 5:
Probability of Observing at Least One (Serious) Adverse Event.................................... 87
Table 6:
Sample Size Justification Safety Evaluation in Stage 1 and 2 ....................................... 88

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Approved, Date: 2 October 2018
PROTOCOL AMENDMENTS
Protocol Version 
Issue Date
Original Protocol
20-Mar-2015
Amendment 1
01-May-2015
Amendment 2
30-Nov-2015
Amendment 3
28-Jan-2016
Amendment 4
07-Sep-2016
Amendment 5
04-May-2017
Amendment 6
20-June-2018
Amendment 7
02-Oct-2018
Amendments below are listed beginning with the most recent amendment.
Amendment_7 (02-Oct-2018)
The overall reason for the amendment: This amendment is created to update the information on study unblinding 
and to update information on the roll-over of subjects from the VAC52150EBL3001 study to the 
VAC52150EBL3005 study.
The changes made to the clinical protocol VAC52150EBL3001 are listed below, including the rationale of each 
change and a list of all applicable sections.
Rationale: It is clarified that for each age group of Stage 2, subjects and study-site personnel (except for 
unblinded qualified study-site personnel with primary responsibility for study vaccine preparation and dispensing)
will be blinded to the study vaccine allocation until the last subject in that age group has completed at least the 6
month post-boost visit or discontinued earlier and the database has been locked for that part.
SYNOPSIS
3.1 Overview of Study Design
5 TREATMENT ALLOCATION AND BLINDING
11 STATISTICAL METHODS
Rationale: It is clarified that roll-over of subjects in Stage 2 of the VAC52150EBL3001 to the 
VAC52150EBL3005 study will occur after unblinding of the VAC52150EBL3001 data and that only those 
subjects who received Ad26.ZEBOV and/or MVA-BN-Filo may roll-over.
SYNOPSIS
3.1 Overview of Study Design
Rationale: The protocol is adjusted to indicate that, in case there would have been females in Stage 1 of the study 
who became pregnant and met the criteria as outlined in the protocol, they would have been allowed to enroll in 
the follow-up study VAC52150EBL3005.
SYNOPSIS
3.1 Overview of Study Design
Rationale: Minor corrections have been made.
1.2.3 Known Risks
1.2.4 Potential Risks
3.1 Overview of Study Design
14.4 Vaccine Accountability

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Approved, Date: 2 October 2018
Amendment_6 (20-June-2018)
The overall reason for the amendment: This amendment is created to replace information on Study 
VAC52150EBL4001 with information on the new planned long-term follow-up Study VAC52150EBL3005, to 
remove references to the Menveo® vaccine, to add information on the requirement to consent or to give positive 
assent for subjects who turn 18 or 7 years of age, respectively, during active participation in the study, and to add
that subjects in Stage 1 and Stage 2 may be contacted approximately 1 month after their last study visit to inquire 
after their general health status.
The changes made to the clinical protocol VAC52150EBL3001 are listed below, including the rationale of each 
change and a list of all applicable sections.
Rationale: The planned VAC52150 Vaccine Development Roll-over Study, VAC52150EBL4001, has been 
replaced by the long-term follow-up Study VAC52150EBL3005. Subjects enrolled in VAC52150EBL3001 who 
were eligible to be followed-up in the VAC52150EBL4001 study (ie, female subjects who became pregnant with 
estimated conception within 28 days after vaccination with MVA-BN-Filo [or placebo] or within 3 months after 
vaccination with Ad26.ZEBOV [or active control vaccine] and children born to vaccinated female subjects who 
became pregnant with estimated conception within 28 days after vaccination with MVA-BN-Filo [or placebo] or 
within 3 months after vaccination with Ad26.ZEBOV [or active control vaccine]) will now be eligible to roll-over 
to
the VAC52150EBL3005 study as will all other subjects enrolled in Stage 2 of the current 
Study VAC52150EBL3001. VAC52150EBL3005 will be a long-term follow-up study evaluating up to 5-year 
safety and binding antibody persistence of Ad26.ZEBOV at a dose of 5x1010 viral particles (vp) followed by 
MVA-BN®-Filo at a dose of 1x108 TCID50 56 days later. Since subjects in Stage 1 will be asked to consent to a 
third open-label vaccination at least 2 years post-prime vaccination, these subjects will not be eligible for long-
term follow-up in Study VAC52150EBL3005.
SYNOPSIS
1.2.4 Potential Risks
1.2.6 Overall Benefit/Risk Assessment
3.1 Overview of Study Design
9.1.5 Long-Term Follow-Up
9.x VAC52150 Vaccine Roll-over Study
12.3.4 Pregnancy
Rationale: To allow for WHO-prequalified MenACWY vaccines, other than Menveo®, to be used in the active 
control group of Stage 2 of the current study VAC52150EBL3001, references to the Tradename Menveo® have 
been deleted from the protocol.
SYNOPSIS
1.2.1 Known Benefits
1.2.3 Known Risks
1.2.5 Unknown Risks
6 DOSAGE AND ADMINISTRATION
14.1.3 MenACWY
REFERENCES
ATTACHMENTS
Rationale: The prohibitions and restrictions criterion 4.1 was clarified, ie, subjects should not receive inactivated 
vaccines from 15 days before or after administration of prime and boost vaccination and 15 days before or after 
administration of the third vaccination in Stage 1 (previously 15 days before or after administration of any study 
vaccine).
4.3 Prohibitions and Restrictions

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Approved, Date: 2 October 2018
Rationale: It has been clarified that subjects who turn 18 or 7 years old while they are still active participants in 
the study will need to consent or give positive assent, respectively, to continue participation in the study.
16.2.3 Informed Consent
Rationale: Subjects in Stage 1 and Stage 2 may be contacted approximately 1 month after their last study visit to 
inquire after their general health status.
SYNOPSIS
TIME AND EVENTS SCHEDULE – Stage 1
TIME AND EVENTS SCHEDULE – Stage 1 Continued (Third Vaccination)
TIME AND EVENTS SCHEDULE – Stage 2
3.1 Overview of Study Design
9.1.5 Long-Term Follow-Up
10.1 Completion
Rationale: Minor textual changes, clarifications and corrections have been made.
1 INTRODUCTION
5 TREATMENT ALLOCATION AND BLINDING
9.1.2 Screening Phase
9.1.3 Vaccination Period
9.3.2 Evaluations
16.1 Study-Specific Design Considerations
17.9.1 Study Completion
Attachment 1: Schematic Presentation of the IDMC Schedule for the Prime and Boost Vaccination
Attachment 4: Toxicity Tables for Use in Trials Enrolling Healthy Adults and Adolescents
Attachment 5: Toxicity Tables for Use in Trials Enrolling Children Greater Than 3 Months of Age

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Approved, Date: 2 October 2018
Amendment_5 (04-May-2017) 
The overall reason for the amendment: This amendment is developed in response to emerging clinical data and 
changes to the global clinical development plan.
Immunogenicity data from a Phase 1 study of the monovalent vaccine program (VAC52150EBL1002)
demonstrated stability of the binding antibody response out to one year following prime-boost regimens with 
Ad26.ZEBOV/MVA-BN-Filo (or the reverse). A third vaccination using Ad26.ZEBOV at 5x1010 vp was given at 
the one-year time point leading to a marked and rapid increase in the binding antibody responses within 7 days (at 
least 10-fold). The marked and rapid rise was generally independent of the antecedent prime-boost regimen. The 
profile of the antibody response strongly suggests that robust anamnestic responses can be induced after re-
exposure to an EBOV antigen, in this case mimicked by a third vaccination. This amendment proposes
administration of a third vaccination using Ad26.ZEBOV at least 2 years post prime for subjects in Stage 1 in 
order to extend the findings to an African population.
This amendment also proposes to double the number of children in each age group in Stage 2 to expand the safety 
and immunogenicity data in each age group. The follow-up period of adults in Stage 2 will be extended to 2 years 
post prime to monitor for safety and persistence of the immune response.
Furthermore, the enrollment of subjects from VAC52150EBL3001 to the VAC52150EBL4001 roll-over study is 
limited to female subjects who became pregnant with estimated conception within 28 days after vaccination with 
MVA-BN-Filo (or placebo) or within 3 months after vaccination with Ad26.ZEBOV (or active control vaccine) 
and children born to vaccinated female subjects who became pregnant with estimated conception within 28 days 
after vaccination with MVA-BN-Filo or within 3 months after vaccination with Ad26.ZEBOV, unless local 
regulations have additional requirements for follow up.
The changes made to the clinical protocol VAC52150EBL3001 are listed below, including the rationale of each 
change and a list of all applicable sections.
Rationale: A third vaccination using Ad26.ZEBOV will be administered to subjects in Stage 1 at least 2 years 
post-prime in order to confirm and extend the immunogenicity findings from a Phase 1 study.
SYNOPSIS
TIME AND EVENTS SCHEDULE – Stage 1
TIME AND EVENTS SCHEDULE – Stage 1 Continued (Third Vaccination)
1.2.4 Potential Risks
1.2.6 Overall Benefit/Risk Assessment
1.3 Overall Rationale for the Study
2.1 Objectives
3 STUDY DESIGN AND RATIONALE
4.3 Prohibitions and Restrictions
5 TREATMENT ALLOCATION AND BLINDING
6 DOSAGE AND ADMINISTRATION
8 PRESTUDY AND CONCOMITANT THERAPY
9.1.1 Overview
9.1.2 Screening Phase
9.1.3 Vaccination Period
9.1.4 Post-Boost and Post-Third Vaccination Period
9.1.5 Long-Term Follow-Up
9.1.8 VAC52150 Vaccine Roll-over Study
9.3.1 Endpoints
9.3.2 Evaluations
10.1 Completion
10.3 Contraindications to Vaccination

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Approved, Date: 2 October 2018
11.3 Sample Size Determination
12.3.1 All Adverse Events
12.3.4 Pregnancy
15 STUDY-SPECIFIC MATERIALS
16.1 Study-Specific Design Considerations
17.4 Source Documentation
Rationale: The number of children in each age group in Stage 2 will be increased to expand the safety and 
immunogenicity data in each age group. To compensate for an expected higher variability in immunogenicity 
parameters, sample size will be doubled for each age group. Doubling the sample size will compensate for a 41% 
higher standard deviation (sqrt(2)=1.41).
SYNOPSIS
1.2.6 Overall Benefit/Risk Assessment
3.1 Overview of Study Design
4 SUBJECT POPULATION
6 DOSAGE AND ADMINISTRATION
11.3 Sample Size Determination
Rationale: The follow-up period of adults in Stage 2 will be expanded to 2 years post prime to monitor for safety 
and persistence of the immune response.
SYNOPSIS
TIME AND EVENTS SCHEDULE – Stage 2
1.2.6 Overall Benefit/Risk Assessment
3.1 Overview of Study Design
5 TREATMENT ALLOCATION AND BLINDING
9.1.1 Overview
9.1.5 Long-Term Follow-Up
9.3.2 Evaluations
10.1 Completion
12.3.1 All Adverse Events

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Approved, Date: 2 October 2018
Rationale: The original development plan (at the time of the ongoing Ebola epidemic in Africa) was an 
accelerated plan with the anticipation of conducting Phase 3 efficacy studies (with limited safety data collection) 
shortly after Phase 1 and in parallel with Phase 2. The sponsor designed the VAC52150EBL4001 study for the 
extended follow-up of serious adverse events to enhance the ability for signal detection of rare events. Since there 
is no longer an ongoing Ebola epidemic, it is currently not possible to conduct a parallel Phase 3 efficacy study as 
part of an accelerated development plan. The ongoing Phase 2 and 3 studies will continue long-term follow-up in 
a placebo-controlled manner until agreement to unblind has been achieved. Placebo-controlled blinded data 
during long-term follow-up will provide high quality data on long-term safety and will supplement the open-label 
registry data. In this study, the requirement for entrance to the VAC52150EBL4001 roll-over study is limited to 
female subjects who became pregnant with estimated conception within 28 days after vaccination with MVA-BN-
Filo (or placebo) or within 3 months after vaccination with Ad26.ZEBOV (or active control vaccine) and children 
born to vaccinated female subjects who became pregnant with estimated conception within 28 days after 
vaccination with MVA-BN-Filo (or placebo) or within 3 months after vaccination with Ad26.ZEBOV (or active 
control vaccine), unless local regulations have additional requirements for follow up. Following these children for 
a total of five years was a commitment made to the relevant health authorities.
SYNOPSIS
3.1 Overview of Study Design
9.1.8 VAC52150 Vaccine Roll-over Study
12.3.4 Pregnancy
Rationale: The secondary objectives and endpoints were limited to immune responses measured by ELISA at 
21 days post boost. Immune responses measured by ELISA at all other relevant time points were shifted to the 
exploratory objectives and endpoints. As the exploratory endpoints can be presented in a separate biomarker 
report, there will be no delay in the preparation of the final Clinical Study Report. 
SYNOPSIS
2.1 Objectives
9.2.1 Endpoints
Rationale: As there is no analysis planned for the immunogenicity sample taken on Day 29 in children from 
Stage 2, this sample was removed.
TIME AND EVENTS SCHEDULE – Stage 2
9.1.1 Overview
9.1.3 Vaccination Period
16.1 Study-Specific Design Considerations
Rationale: The statistical methods for clinical laboratory tests, vital signs, and physical examination were 
revised. Since only small mean fluctuations are expected, limited interest will be on the summary statistics over 
time and the analyses will focus on worst abnormalities and toxicity gradings.
11.5 Safety Analyses
Rationale: As the lab values mentioned in inclusion criterion 4 (Stage 2) are not fully in line with the normal lab 
ranges, especially for children, this inclusion criteria was modified to keep it more general, without specifying 
any lab values.
4.1 Inclusion Criteria
Rationale: Exclusion criterion 13 of Stage 2, describing the weight restrictions for children, was modified to 
reflect the data according to the World Health Organization (WHO) and Centers for Disease Control and 
Prevention (CDC) growth charts.
4.2 Exclusion Criteria

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Approved, Date: 2 October 2018
Rationale: To ensure consistency regarding the completion of the TOU for children whose parent or guardian are 
not part of the study compared to those who are enrolled to the study, and to clarify the procedures to follow in 
case of recruitment of multiple children of the same family, the language regarding completion of the TOU has 
been changed. 
TIME AND EVENTS SCHEDULE – Stage 2
9.1.2 Screening Phase
16.1 Study-Specific Design Considerations
Rationale: Minor textual changes and corrections have been made.
SYNOPSIS
TIME AND EVENTS SCHEDULE – Stage 1
TIME AND EVENTS SCHEDULE – Stage 2
ABBREVIATIONS
1.1 Background
1.2.1 Known Benefits
1.2.4 Potential Risks
1.2.6 Overall Benefit/Risk Assessment
1.3 Overall Rationale for the Study
2.2 Hypothesis
3.1 Overview of Study Design
4.1 Inclusion Criteria
6 DOSAGE AND ADMINISTRATION
8 PRESTUDY AND CONCOMITANT THERAPY
9.1.3 Vaccination Period
9.1.5 Long-Term Follow-Up
9.1.8 VAC52150 Vaccine Roll-over Study
9.3.2 Evaluations
11 STATISTICAL METHODS
11.4 Immunogenicity Analyses
11.7 Independent Data Monitoring Committee (IDMC)
11.7.1 Safety
12.3.4 Pregnancy
15 STUDY-SPECIFIC MATERIALS
16.2.3 Informed Consent
Rationale: The protocol has been updated to be in line with the current protocol template (version 
1 November 2016).
TITLE PAGE 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Approved, Date: 2 October 2018
Amendment_4 (07-Sep-2016)
The overall reason for the amendment: The sponsor halted vaccinations in the clinical program following a 
case of Miller Fisher syndrome after receipt of MVA-BN-Filo or placebo in study VAC52150EBL2001, as well 
as following reports of mild transient paresthesia in the same clinical study that required further assessment to 
rule out a neurologic and autoimmune event. The current study was paused until the updated study-specific 
informed consent form had been approved to inform the study participants on the additional safety information. 
As a result of the pause, some subjects were outside the protocol-defined boost vaccination window. Based on the 
request of the Agence Nationale de Sécurité du Médicament et des produits de santé (ANSM) for study 
VAC52150EBL2001 in response to the Miller Fisher case, the sponsor has decided to implement the collection of 
neurologic and autoimmune events (“Immediate Reportable Events”) throughout the entire clinical development 
plan.
The changes made to the clinical protocol VAC52150EBL3001 are listed below, including the rationale of each 
change and a list of all applicable sections.
Rationale: As requested by the ANSM, wording on the collection of “Immediate Reportable Events” was added 
after one subject in the study VAC52150EBL2001 experienced a serious and very rare condition called “Miller 
Fisher syndrome” about a month after boost vaccination with either MVA-BN-Filo or placebo. Although the 
event was considered to be unrelated to the vaccine, measures were implemented for the entire clinical 
development program.
SYNOPSIS
Time and Events Schedules
ABBREVIATIONS
1.1 Background
1.2.6 Overall Benefit/Risk Assessment
3.1 Overview of Study Design
9.1.2 Screening Phase
9.1.3 Vaccination Period
9.1.5 Long-Term Follow-Up
9.3 Safety
12.1.1 Adverse Event Definitions and Classifications
12.2 Special Reporting Situations
12.3.1 All Adverse Events
12.3.3 Immediate Reportable Events
Rationale: As a result of the pause, some subjects will be outside the protocol-defined boost vaccination window. 
Information was added to clarify the procedures that need to be followed for these subjects.
SYNOPSIS
1.2.4 Potential Risks
3.1 Overview of Study Design
11.1 Analysis Sets
Rationale: As a consequence of the pause, delays in unblinding are expected. Further details regarding 
enrollment into the VAC52150 roll-over study have been added, such as the inclusion of subjects from the control 
arm before unblinding of the current study.
SYNOPSIS
3.1 Overview of Study Design
9.1.8 VAC52150 Vaccine Roll-over Study

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Approved, Date: 2 October 2018
Rationale: As a result of the pause, subjects whose screening period was longer than the protocol-defined 28 days
will be allowed to rescreen once.
Time and Events Schedules
9.1.2 Screening Phase
Rationale: Stage 1 of the study is extended for 24 months beyond Day 360, for long-term follow-up of safety and 
immunogenicity. Subjects in Stage 1 will not be approached to consent for enrollment into the VAC52150 
Vaccine Roll-over Study.
SYNOPSIS
Time and Events Schedules
1.2.6 Overall Benefit/Risk Assessment
3.1 Overview of Study Design
9.1.2 Screening Phase
9.1.5 Long-Term Follow-Up
9.3 Safety
10.1 Completion
11 STATISTICAL METHODS
12.3.1 All Adverse Events
Rationale: The visits after the boost vaccination in Stage 2 have been renamed to reflect the timing relative to the 
boost vaccination, to clarify that the intention of the visit is to follow compared to boost rather than to prime, 
especially for subjects who are out of window due to the pause. This is consistent with other studies in the 
VAC52150 clinical program.
Time and Events Schedules
9.1.3 Vaccination Period
9.1.4 Post-Boost Vaccination Period 
9.1.5 Long-Term Follow-Up
9.3.2 Evaluations
Rationale: As per the prescribing information of MenACWY (MENVEO®), 2 doses are recommended for 
children aged 12 to 24 months, with an interval of 3 months between the doses. Children aged less than 2 years at 
the time of the initial vaccination (randomization) will receive a third vaccination on the 3-month post-boost visit
with either MenACWY (control arm) or placebo (Ad26.ZEBOV/MVA-BN-Filo arm). 
SYNOPSIS
Time and Events Schedules
6 DOSAGE AND ADMINISTRATION
9.1.3 Vaccination Period
9.1.4 Post-Boost Vaccination Period 
9.3.1 Endpoints
9.3.2 Evaluations
Rationale: The 3-month post-boost visit (previously named Day 156) in Stage 2 is only applicable for children 
aged less than 2 years at the time of randomization. This time point was removed for the other populations based 
on the availability of new data from other studies showing persistent immune responses up to 1 year post 
vaccination.
SYNOPSIS
Time and Events Schedules
6 DOSAGE AND ADMINISTRATION
9.1.1 Overview
9.1.4 Post-Boost Vaccination Period 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Approved, Date: 2 October 2018
Rationale: Safety assessments have been added to the Day 29 and 6-month post-boost visit for subjects in 
Stage 2, consistent with other studies in the VAC52150 clinical program.
Time and Events Schedules
9.1.3 Vaccination Period
9.1.5 Long-Term Follow-Up
Rationale: As requested by the Pharmacy Board of Sierra Leone (PBSL), subjects in Stage 2 who received a 
meningitis vaccine in the past are excluded. 
4.2 Exclusion Criteria
Rationale: The use of analgesic/antipyretic medications and non-steroidal anti-inflammatory drugs (NSAIDs) is 
no longer limited to only 24 hours after vaccination. This measure was previously implemented to avoid missing 
infection with Ebolavirus while it was still circulating. 
4.3 Prohibitions and Restrictions
8 PRESTUDY AND CONCOMITANT THERAPY
Rationale: As requested by the Food and Drug Administration (FDA) in response to Amendment #26 to 
IND16280 the analysis sets have been re-defined. Furthermore, it was clarified that the primary analysis in 
Stage 2 will be performed separately for adults and children.
SYNOPSIS
5 TREATMENT ALLOCATION AND BLINDING
11 STATISTICAL METHODS
Rationale: As likely all subjects will have data collected for onsite-assessment or diary data for solicited AEs, 
there is no need to make this distinction.
11.5 Safety Analyses
Rationale: Wording added to clarify that birth control methods should be applied by sexually active female 
participants.
Time and Events Schedules
1.2.4 Potential Risks
4.1 Inclusion Criteria
4.3 Prohibitions and Restrictions
Rationale: Safety information following MVA-BN-Filo vaccine administration based on the pooled safety data 
from studies VAC52150EBL1001 and VAC52150EBL1002 has been included.
1.1 Background
1.2.3 Known Risks
1.2.4 Potential Risks
REFERENCES
Rationale: Name change from Crucell Holland B.V. to Janssen Vaccines & Prevention B.V.
Title Page
SYNOPSIS
1 INTRODUCTION
1.3 Overall Rationale for the Study
14.1.1 Ad26.ZEBOV
14.1.2 MVA-BN-Filo
REFERENCES

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Approved, Date: 2 October 2018
Rationale: The protocol has been updated to be in line with the current protocol template (version 6 June 2016).
4 SUBJECT POPULATION
17.4 Source Documentation
Rationale: Minor textual changes have been made, in addition to modifications for clarity and updates to be in 
line with other current protocols and the current Investigator Brochures.
Throughout the protocol.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Approved, Date: 2 October 2018
Amendment_3 (28-Jan-2016) 
The overall reason for the amendment: This amendment is written to delete Stage 3.
The main objective of the originally planned Stage 3 of the study was to assess vaccine effectiveness in 
preventing cases of Ebola Virus Disease (EVD). As active human-to-human transmission is no longer occurring 
in Sierra Leone, the window of opportunity to evaluate the effectiveness is closed for this epidemic unless there is 
a resurgence. As a result, the Stage 3 component has been removed. 
Rationale: Deletion of Stage 3 and minor changes
Title Page
SYNOPSIS
Time and Events Schedules
ABBREVIATIONS
1 INTRODUCTION
1.2.2 Potential Benefits
1.2.4 Potential Risks
1.2.6 Overall Benefit/Risk Assessment
1.3 Overall Rationale for the Study
2.1 Objectives
2.x Hypothesis
3 STUDY DESIGN AND RATIONALE
3.1 Overview of Study Design
3.2 Study Design Rationale
4 SUBJECT POPULATION
4.1 Inclusion Criteria
4.2 Exclusion Criteria
4.3 Prohibitions and Restrictions
5 TREATMENT ALLOCATION AND BLINDING
6 DOSAGE AND ADMINISTRATION
8 PRESTUDY AND CONCOMITANT THERAPY
9.1.1 Overview
9.1.2 Screening Phase
9.1.3 Vaccination Period
9.1.4 Post-Boost Vaccination Period 
9.1.5 Long-Term Follow-Up
9.1.6 Evaluation of Fever
9.1.x Active and Passive Surveillance of Cases
9.1.8 VAC52150 Vaccine Roll-over Study
9.x Effectiveness
9.x Endpoints
9.x Evaluations
9.x Contact Sub-Study
9.2.2 Evaluations
9.3.1 Endpoints
9.3.2 Evaluations
10.1 Completion
10.4 Withdrawal from the Study
11 STATISTICAL METHODS
11.1 Analysis Sets
11.2 Subject Information
11.3 Sample Size Determination
11.x Effectiveness Analyses
11.x Primary Analysis
11.x Secondary Analysis
11.5 Safety Analyses

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Approved, Date: 2 October 2018
11.7 Independent Data Monitoring Committee (IDMC)
11.7.1 Safety
11.x Effectiveness
11.x Stage 3
12.1.1 Adverse Event Definitions and Classifications
12.3.1 All Adverse Events
14.2 Packaging and Labeling
15 STUDY-SPECIFIC MATERIALS
16.2.3 Informed Consent
16.2.5 Long-Term Retention of Samples for Additional Future Research
17.2.1 Regulatory Approval/Notification
17.4 Source Documentation
17.5 Case Report Form Completion
17.8 Monitoring
17.9.1 Study Completion
REFERENCES
Attachment 3 Fever Management Algorithm

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Approved, Date: 2 October 2018
Amendment_2 (30-Nov-2015)
The overall reason for the amendment: This amendment is written to adapt Stage 2.
With the declaration of Sierra Leone as Ebola free on 7 November 2015, and in line with the regulatory feedback
from FDA and EMA, a control arm has been added to Stage 2 of the study. Stage 2 will now be an individually 
randomized, double-blinded, active-controlled study. As a consequence, the sample size has been increased to 
approximately 688 subjects, including some 288 children aged 1 to 17 years. Other key changes include an 
adjustment in the age limits of the 2 younger age groups (from 1-5 years and 6-11 years to 1-3 years and 
4-11 years) as suggested by FDA/EMA feedback. A 3:1 randomization was chosen for the study to expose as 
many subjects to the vaccine as possible while still having a robust number of control subjects. Subjects in the 
active control group will receive the WHO-prequalified vaccine MenACWY (MENVEO®, Novartis, which is 
indicated for active immunization of persons at risk of exposure to Neisseria meningitidis groups A, C, W135 and 
Y) as prime on Day 1 and placebo as boost on Day 57. Children younger than 2 years of age will receive a second 
dose of MenACWY as boost on Day 57 instead of placebo (as per the prescribing information). Blood samples 
will be collected for immunogenicity and for safety laboratory assessments, and diaries will be used for collection 
of solicited local and systemic adverse events, including reactogenicity. No effectiveness data will be captured in 
Stage 2.
The main objective of the originally planned Stage 3 of the study was to assess vaccine effectiveness in 
preventing cases of Ebola virus disease (EVD). As active human-to-human transmission is no longer occurring in 
Sierra Leone, the window of opportunity to evaluate the effectiveness is closed for this epidemic unless there is a 
resurgence. The Stage 3 component, that was shaded in grey throughout the protocol to facilitate the review of 
the Sierra Leone Pharmacy Board and Ethics Committee to focus on the Stage 1 and Stage 2 component of the 
study, continues to be greyed out. 
Rationale: Changes of Stage 2
Title Page
SYNOPSIS
Time and Events Schedules
ABBREVIATIONS
DEFINITIONS OF TERMS
1.2 Risk Benefit Section
2.1 Objectives
3 STUDY DESIGN AND RATIONALE
4 SUBJECT POPULATION
5 TREATMENT ALLOCATION AND BLINDING
6 DOSAGE AND ADMINISTRATION
9.1.1 Overview
9.1.2 Screening Phase
9.1.3 Vaccination Period
9.1.4 Post-Boost Vaccination Period 
9.1.5 Long-Term Follow-Up
9.2 Effectiveness
9.2.1 Endpoints
9.2.2 Evaluations
9.3.1 Endpoints
9.3.2 Evaluations
10.1 Completion
11.3 Sample Size Determination

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Approved, Date: 2 October 2018
11.4 Immunogenicity Analyses
11.5 Safety Analyses
11.7.1 Safety
11.8.2 Effectiveness
11.9 Pausing Rules
12.1.1 Adverse Event Definitions and Classifications
12.3.1 All Adverse Events
14.1.3 MenACWY
14.1.4 Placebo
14.3 Preparation, Handling and Storage
15 STUDY-SPECIFIC MATERIALS
16.1 Study-Specific Design Considerations
17.8 Monitoring
17.9.1 Study Completion
REFERENCES
Attachment 1 Schematic Presentation of the IDMC Schedule for the Prime and Boost Vaccination
Rationale: The immunogenicity objective for Stage 1 has been made a secondary instead of a primary objective 
for alignment with Stage 2. 
SYNOPSIS
2.1 Objectives
3.2 Study Design Rationale
Rationale: The protocol is broadened to allow countries other than Sierra Leona to potentially participate in the 
study. Including additional countries will accelerate availability of sufficient data for submission purposes and 
will allow for additional countries to engage in Stage 2 of the study, and in Stage 3 in case of a resurgence of the 
Ebola epidemic in their country.
SYNOPSIS
3.1 Overview of Study Design
4 SUBJECT POPULATION
4.3 Prohibitions and Restrictions
16.2.3 Informed Consent
Rationale: A schematic presentation of the IDMC schedule has been added to clarify the process.
SYNOPSIS
3.1 Overview of Study Design
11.7 Independent Data Monitoring Committee (IDMC)
Attachment 1 Schematic Presentation of the IDMC Schedule for the Prime and Boost Vaccination
Rationale: Harmonization of the body temperature designated as fever (≥38.0°C) has been done for Stage 2 and 
3. The temperature in Stage 1 will not be adapted as all subjects will be vaccinated by the time this amendment 
will go into effect.
SYNOPSIS
4.2 Exclusion Criteria
10.3 Contraindications to Vaccination

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Approved, Date: 2 October 2018
Rationale: It has been clarified that immunological assays to be performed will depend on assay and/or sample 
availability. 
SYNOPSIS
9.2 Immunogenicity
16.2.5 Long-Term Retention of Samples for Additional Future Research
Rationale: The blood volumes to be collected have been adapted to reflect a change in the collection tubes for 
immunogenicity samples in children, and RT-PRC testing for export of samples.
Time and Events Schedules
9.1.1 Overview
16.1 Study-Specific Design Considerations
Rationale: For Stage 2, a Day 156 (for adults only) and Day 240 time point was chosen, in addition to the 
already specified time points, to draw blood for an immunogenicity assay.
Time and Events Schedules
9.1.4 Post-Boost Vaccination Period 
9.1.5 Long-Term Follow-Up
Rationale: The introduction was aligned with the Edition 3 of the Ad26.ZEBOV Investigator Brochure
1 INTRODUCTION
REFERENCES
Rationale: The VAC52150 Vaccine Development Registry has been replaced by a roll-over study
1.2.4 Potential Risks
9.1.8 VAC52150 Vaccine Roll-over Study
12.3.4 Pregnancy
Rationale: Malaria and other endemic parasitic diseases can lead to a decrease in white blood cell count 
compared to that found in subjects in non-malaria regions. Therefore, based on the laboratory normal ranges 
expected in West Africa, the cut-off for inclusion in Stage 2 has been adapted from 4,000 to 3,500 white blood 
cells per mm³.
4.1 Inclusion Criteria
Rationale: Text on hemoglobin, hematocrit and red blood cell count in inclusion criterion #4 has been removed
as this is already covered sufficiently by exclusion criterion #4. This is applicable to Stage 2.
4.1 Inclusion Criteria
Rationale: Screening failures in Stage 1 and 2 will be allowed to volunteer for participation at a later stage.
4.1 Inclusion Criteria
4.2 Exclusion Criteria
Rationale: To align with the Phase 2 protocols, subjects in Stage 2 can retake the Test of Understanding twice 
instead of once. 
4.1 Inclusion Criteria
9.1.2 Screening Phase
16.1 Study-Specific Design Considerations

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Approved, Date: 2 October 2018
Rationale: Based on the laboratory normal ranges expected in West Africa, the minimum number of platelets in 
inclusion criterion #4 has been adapted from 150,000 to 100,000. This is applicable to Stage 2. The adult toxicity 
grading scale for platelets has been adapted to reflect this change.
4.1 Inclusion Criteria
REFERENCES
Attachment 4 Toxicity Tables for Use in Trials Enrolling Healthy Adults
Rationale: Text has been added to further clarify the community engagement process. 
5 TREATMENT ALLOCATION AND BLINDING
Rationale: To keep all options open it is specified that interim analyses may be planned to support regulatory 
purposes and additional text on blinding for interim analyses in Stage 2 is added.
SYNOPSIS
5 TREATMENT ALLOCATION AND BLINDING
11 STATISTICAL METHODS
11.6 Interim Analysis
Rationale: Evaluations in case of fever have been clarified and a fever management algorithm has been added. In 
case a subject has fever, but does not meet the EVD definition, an unscheduled blood sample may be taken to 
perform a PCR test to exclude EVD. To prevent new malaria infections in the study subjects as much as possible, 
subjects in Stage 1 and 2 will receive insecticide-treated bed nets to reduce the incidence of malaria-induced 
fever.
9.1.1 Overview
9.1.6 Evaluation of Fever
Attachment 3 Fever Management Algorithm
Rationale: Clarification on criteria for contraindication of boost vaccination
10.3 Contraindications to Vaccination
Rationale: Toxicity grading tables will be used instead of laboratory normal ranges
11.5 Safety Analyses
Attachment 4: 
Toxicity Tables for Use in Trials Enrolling Healthy Adults
Attachment 5: 
Toxicity Tables for Use in Trials Enrolling Children Greater Than 3 Months of Age
Rationale: Small adjustments for clarification
Throughout the protocol

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Approved, Date: 2 October 2018
Amendment_1 (01-May-2015)
The overall reason for the amendment: This amendment is written in response to the Assisted Review of the 
Janssen Ebola Zaire Vaccine Clinical Trials Application meeting of 8-10 April 2015. It only concerns changes to 
the Stage 1 and Stage 2 components of the protocol. Any text related to the Stage 3 component of the protocol is 
shaded in grey and will be reviewed at a later stage. 
Applicable Section(s)
Description of Change(s)
Rationale: The following changes were made on request of the Health Authorities:
Title Page
SYNOPSIS
3 STUDY DESIGN AND RATIONALE
17.2.1 Regulatory Approval/Notification
Explanation is provided that the amendment only concerns changes 
to the Stage 1 and Stage 2 components of the protocol, and that any 
text related to the Stage 3 component will be reviewed at a later 
stage. The title of the study has also been updated to reflect the 
staged approach.
Title Page
1 INTRODUCTION
1.3 Overall Rationale for the Study
The role of the Ministry of Health and Sanitation (MoHS), College 
of Medicine and Allied Health Sciences (COMAHS), and GOAL 
has been acknowledged. 
SYNOPSIS
Time and Events Schedules
1.2.6 Overall Benefit/Risk Assessment
3.1 Overview of Study Design
4 SUBJECT POPULATION
4.1 Inclusion Criteria
5 TREATMENT ALLOCATION AND 
BLINDING
9.1.4 Post-Boost Vaccination Period
9.1.5 Long-Term Follow-Up
9.3.2 Evaluations
16.2.3 Informed Consent
Active surveillance will be performed in a sentinel subsample of 
5,000 subjects from the delayed-vaccination clusters who have 
provided individual consent for this. Subjects in both sentinel 
subsamples will be followed-up for 6 months.
SYNOPSIS
Time and Events Schedules
3.1 Overview of Study Design
9.1.1 Overview
9.1.4 Post-Boost Vaccination Period
9.1.5 Long-Term Follow-Up
Subjects from Stage 3 will be followed-up for 1 year for 
immunogenicity. 
SYNOPSIS
1.2.6 Overall Benefit/Risk Assessment
3.1 Overview of Study Design
11.3 Sample Size Determination
Subjects in Stage 2 will be enrolled in 4 age groups.
SYNOPSIS
2.1 Objectives
Primary study objectives are defined for Stage 1 and Stage 2.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Approved, Date: 2 October 2018
Applicable Section(s)
Description of Change(s)
SYNOPSIS
3.1 Overview of Study Design
11.7 Independent Data Monitoring 
Committee (IDMC)
The review of the Independent Data Monitoring Committee 
(IDMC) has been aligned with having 4 age groups in Stage 2. In 
addition, the IDMC review will include data from Phase 1 and 
Phase 2 studies, and will also take into consideration cardiac or 
hematological abnormalities.
SYNOPSIS
5 TREATMENT ALLOCATION AND 
BLINDING
9.2.1 Endpoints
9.2.2 Evaluations
11 STATISTICAL METHODS
REFERENCES
Clarifications have been added to the statistical sections/analyses.
It has been described that the adjudication panel will be blinded.
SYNOPSIS
9.2.1 Endpoints
11.4.1 Primary Analysis
Clarification is added that the primary analysis will be done on the 
primary analysis set, which is a subset of the intent-to-treat (ITT)
analysis set. 
SYNOPSIS
9.2.2 Evaluations
The Sierra Leone case definitions for Ebola (adapted from World 
Health Organization [WHO]) are used.
Time and Events Schedules
1.2.4 Potential Risks
4.1 Inclusion Criteria
4.3 Prohibitions and Restrictions
9.1.2 Screening Phase
Contraception has been added to the inclusion criteria.
Time and Events Schedules
4.1 Inclusion Criteria
16.2.3 Informed Consent
The assent procedure in children/adolescents must be witnessed 
and documented. There will be no separate assent form.
Time and Events Schedules
4.1 Inclusion Criteria
9.1.2 Screening Phase
16.1 Study-Specific Design Considerations
16.2.3 Informed Consent
Attachment 2:
Test of Understanding 
(TOU)
The test of understanding (TOU) will be administered after 
reading, but before signing the informed consent form (ICF).
Time and Events Schedules
4.3 Prohibitions and Restrictions
8 PRESTUDY AND CONCOMITANT 
THERAPY
Prestudy and concomitant therapies will be collected in the sentinel 
cohort from the immediate-vaccination clusters in Stage 3. 
Time and Events Schedules
9.1.3 Vaccination Period
The observation period after each vaccine administration during 
which subjects will stay in the clinic may be extended if deemed 
necessary by the study staff.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Approved, Date: 2 October 2018
Applicable Section(s)
Description of Change(s)
1.2.4 Potential Risks
9.1.8 VAC52150 Vaccine Roll-over Study
12.3.4 Pregnancy
Pregnancy outcomes of all women who become pregnant during 
the study until up to 28 days after the boost vaccination or 
3 months after the prime vaccination (whichever is longer) will be 
collected in the VAC52150 Vaccine Development Registry.
4.1 Inclusion Criteria
9.3.2 Evaluations
Laboratory parameters have been added to the inclusion criteria.
4.2 Exclusion Criteria
4.3 Prohibitions and Restrictions
8 PRESTUDY AND CONCOMITANT 
THERAPY
Subjects should not receive live-attenuated vaccines from 30 days 
before the prime vaccination until 30 days after the boost 
vaccination, and inactivated vaccines from 15 days before or after 
administration of any study vaccine.
4.2 Exclusion Criteria
8 PRESTUDY AND CONCOMITANT 
THERAPY
Anemia has been added to the exclusion criteria. Subjects who 
develop anemia during the study will be treated with supplements.
4.2 Exclusion Criteria
10.3 Contraindications to Vaccination
Illness has been defined.
4.3 Prohibitions and Restrictions
5 TREATMENT ALLOCATION AND 
BLINDING
Text to identify subjects for correct application of the prime-boost 
regimen has been simplified.
9.1.1 Overview
Minor correction (deletion of blood volume for subjects <18 years 
in Stage 1).
9.1.6 Evaluation of Fever
15 STUDY-SPECIFIC MATERIALS
The algorithm for evaluation of fever was adapted.
9.3.2 Evaluations
Text concerning handling of deaths and autopsies was added.
12.1.3 Severity Criteria
Attachment 4: 
Toxicity Tables for Use in 
Trials Enrolling Healthy Adults
Attachment 5: 
Toxicity Tables for Use in 
Trials Enrolling Children Greater Than 3 
Months of Age
Toxicity severity grading tables for adverse event, laboratory data 
and vital signs have been added.
12.3.1 All Adverse Events
Ebola prevention counseling will be provided on the wallet card.
16.2.4 Privacy of Personal Data
Language was added around the transfer of the data to other 
entities and to other countries.
Rationale: The following additional changes were made:
Title Page
The protocol name was added.
Title Page
1 INTRODUCTION
The partners contributing to the study are now listed on the title 
page.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Approved, Date: 2 October 2018
Applicable Section(s)
Description of Change(s)
SYNOPSIS
Time and Events Schedules
3.1 Overview of Study Design
9.1.3 Vaccination Period
9.1.4 Post-Boost Vaccination Period
9.1.5 Long-Term Follow-Up
9.2.2 Evaluations
Subjects from Stage 1 will participate in the immunogenicity 
assessments. An additional sample will be collected on Day 240 
from subjects in Stage 1 and Stage 2. A pre-prime sample will be 
collected from subjects in Stage 3 who participate in the 
immunogenicity sub-study.
ABBREVIATIONS
12.1.1 Adverse Event Definitions and 
Classifications
12.3.1 All Adverse Events
The definition of “SUSAR” was aligned with the new protocol 
template text and the relevant sections of the protocol were updated 
accordingly.
1.1 Background
REFERENCES
The introduction section of the protocol was updated with interim 
results from the ongoing Phase 1 study that is being conducted in 
the United Kingdom (VAC52150EBL1001).
3.2 Study Design Rationale
Study design rationale for Stage 1 and Stage 2 was added.
5 TREATMENT ALLOCATION AND 
BLINDING
The approach for community engagement was clarified.
12.3.2 Serious Adverse Events
Serious adverse event reporting will be done according to local 
regulations.
16.2.5 Long-Term Retention of Samples for 
Additional Future Research
A polymerase chain reaction (PCR) test may be done on all 
immunology samples to ensure Ebola negativity.
17.11 Use of Information and Publication
Text on use of information and publication was updated to reflect 
the agreements between the sponsor and the Consortium.
Attachment 2 Test of Understanding (TOU)
The TOU language has been changed.
Throughout the protocol
Modifications were made throughout the protocol to correct minor 
inconsistencies and/or for clarity.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Approved, Date: 2 October 2018
SYNOPSIS
A Staged Phase 3 Study, Including a Double-Blinded Controlled Stage to Evaluate the Safety and 
Immunogenicity of Ad26.ZEBOV and MVA-BN-Filo as Candidate Prophylactic Vaccines for Ebola
Janssen Vaccines & Prevention B.V. (formerly known as Crucell Holland B.V., hereafter referred to as 
the sponsor), in collaboration with Bavarian Nordic GmbH, Denmark, and in conjunction with the 
London School of Hygiene & Tropical Medicine and Sierra Leonean Ministry of Health and Sanitation
(MoHS) and College of Medicine and Allied Health Sciences (COMAHS), and the Ebola vaccine 
Deployment, Acceptance & Compliance (EBODAC) program, is investigating the potential of a 
prophylactic heterologous prime-boost Ebola vaccine regimen comprising the following 2 candidate 
Ebola vaccines:

Ad26.ZEBOV (JNJ-61210474-AAA) 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 (JNJ-63839880-AAA) (further referred to as 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 AND HYPOTHESIS
OBJECTIVES
The primary objective of Stage 1 is:

To evaluate the safety of a heterologous prime-boost regimen utilizing Ad26.ZEBOV and MVA-
BN-Filo given at a 56-day interval.
The secondary objective of Stage 1 is:

To assess humoral immune responses to a heterologous prime-boost regimen utilizing Ad26.ZEBOV 
and MVA-BN-Filo as measured by an enzyme-linked immunosorbent assay (ELISA) at 21 days 
post-boost vaccination.

To assess the safety and tolerability of a third vaccination using Ad26.ZEBOV administered at least 
2 years post prime.
The exploratory objectives of Stage 1 are:

To assess humoral immune responses to a heterologous prime-boost regimen utilizing Ad26.ZEBOV 
and MVA-BN-Filo as measured by ELISA at other relevant time points.

To assess neutralizing antibody responses directed against EBOV GP induced by the heterologous 
prime-boost regimen as measured by a virus neutralization assay (VNA) depending on sample and 
assay availability.

To assess antibody responses directed against the Ad26 and/or MVA vector as measured by ELISA, 
VNA, and/or plaque reduction neutralization test (PRNT) depending on sample and assay 
availability.

To assess humoral immune responses to a heterologous prime-boost regimen utilizing Ad26.ZEBOV 
and MVA-BN-Filo as measured by ELISA following a third vaccination using Ad26.ZEBOV at 
2 years post prime. 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Approved, Date: 2 October 2018
The primary objective of Stage 2 is:

To evaluate the safety of a heterologous prime-boost regimen utilizing Ad26.ZEBOV and MVA-BN-
Filo given at a 56-day interval compared to an active control vaccine.
The secondary objective of Stage 2 is:

To assess humoral immune responses to a heterologous prime-boost regimen utilizing Ad26.ZEBOV 
and MVA-BN-Filo as measured by an ELISA at 21 days post boost.
The exploratory objectives of Stage 2 are:

To assess humoral immune responses to a heterologous prime-boost regimen utilizing Ad26.ZEBOV 
and MVA-BN-Filo as measured by ELISA at other relevant time points.

To assess neutralizing antibody responses directed against EBOV GP induced by the heterologous 
prime-boost regimen as measured by VNA depending on sample and assay availability. 

To assess antibody responses directed against the Ad26 and/or MVA vector as measured by ELISA, 
VNA, and/or PRNT depending on sample and assay availability.
Note: For the definition of a stage, see section Overview of Study Design below.
HYPOTHESIS
As this study is designed to provide descriptive information regarding safety and immunogenicity without 
formal treatment comparisons, no formal statistical hypothesis testing is planned.
OVERVIEW OF STUDY DESIGN
This is a staged Phase 3 study with an open-label uncontrolled stage (Stage 1) and a double-blinded 
controlled stage (Stage 2) to evaluate the immunogenicity and safety of a heterologous prime-boost 
regimen where Ad26.ZEBOV will be used to prime a filovirus-specific immune response and MVA-BN-
Filo will be used to boost the immune response 56 days later. In Stage 1, a third vaccination using
Ad26.ZEBOV will be administered at least 2 years post prime to subjects who consent to this.
The study will be conducted as follows:

Stage 1: The study will commence with vaccination of a group of approximately 40 adult subjects 
aged 18 years or older. The objective of this initial stage of the study is to evaluate the safety and 
immunogenicity of the prime-boost regimen in the adult Sierra Leonean population.

Stage 2: Approximately 976 subjects aged 1 year or older will be individually randomized in a 
3:1 ratio to receive the Ad26.ZEBOV/MVA-BN-Filo prime-boost regimen or an active control 
vaccine and placebo. The aim is to enroll approximately 400 adults (aged 18 years or older) and 
approximately 576 children aged ≥1 year (with about 192 children in each of the 3 age groups [ie, 
12 to 17 years, 4 to 11 years, and 1 to 3 years, inclusive]). Enrollment will be staggered, starting with 
the eldest age group. The decision to proceed to the next age group will be based on an evaluation by 
an independent data monitoring committee (IDMC) (for details see Section 11.7). Randomization 
will be stratified by age group.
Within each age group of Stage 2, study-site personnel (except for those with primary responsibility for 
study vaccine preparation and dispensing), sponsor personnel (except for specifically designated sponsor 
personnel who are independent of the study) and subjects will be blinded to the study vaccine until all 
subjects in that age group have completed at least the 6 month post-boost visit or discontinued earlier and 
the database has been locked for that age group. Should an interim analysis be performed prior to the 
6 months post-boost visit of the last subject in a given age group, only those involved in the analysis and 
decision making will be unblinded.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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An IDMC will be commissioned for this study. The IDMC will review all available 7-day post-prime 
safety data (including clinical laboratory results) before the first subject of the current cohort receives the 
boost: 
In Stage 1 to determine whether:

the boost vaccination in Stage 1 can be initiated, and

the prime vaccination in Stage 2 (subjects aged 12 to 17 years inclusive) can be initiated.

In Stage 2 (subjects aged 12 to 17 years inclusive) to determine whether:

the boost vaccination of subjects aged 12 to 17 years inclusive can be initiated, and 

the prime vaccination of subjects aged 4 to 11 years inclusive can be initiated.

In Stage 2 (subjects aged 4 to 11 years inclusive) to determine whether:

the boost vaccination of subjects aged 4 to 11 years inclusive can be initiated, and

the prime vaccination of subjects aged 1 to 3 years inclusive can be initiated.

In Stage 2 (subjects aged 1 to 3 years inclusive) to determine whether:

the boost vaccination of subjects aged 1 to 3 years inclusive can be initiated.
The IDMC will also review all cumulative safety data including the 7-day post-boost safety data 
(including clinical laboratory results) to determine if the boost vaccination in the next stage and/or next 
age group can be given. An IDMC meeting will therefore take place with all available data (also including 
the 7-day post-prime safety data within that age group) before boost vaccination will be administered.
A schematic presentation of the IDMC schedule is provided in Attachment 1.
The IDMC will also assess on an ongoing basis the Stage 1 and Stage 2 data as well as data emerging 
from Phase 1 and 2 studies and the status of the epidemic.
While Stage 2 of this study was enrolling, the sponsor halted all vaccinations in the clinical program due 
to the occurrence of a serious and very rare condition, Miller Fisher syndrome, reported in study 
VAC52150EBL2001, as well as following reports of mild transient paresthesia in the same study, until a 
revised informed consent form (ICF) was prepared and approval to restart the current study was granted 
by all relevant authorities. This interruption in dosing affected 98 consented subjects in the current study, 
who had received the prime vaccination. When approval was granted to restart the study under 
Amendment 3, a late boost vaccination was offered to those subjects who had only received the prime 
vaccination, unless participants had withdrawn from the study or were not eligible to receive the boost. 
Vaccinated subjects will follow the same post-boost vaccination schedule as those subjects unaffected by 
the pause. Subjects who refuse or are not eligible to receive the late boost will be encouraged to remain in 
the study to be followed for safety and immunogenicity.
As part of Amendment 4 for this study, Stage 1 was extended for 2 years beyond Day 360 post prime for 
follow-up of safety and immunogenicity. As part of Amendment 5, subjects in Stage 1 who consent to 
this will receive a third vaccination (Ad26.ZEBOV) at least 2 years post-prime vaccination. The follow-
up period for adult subjects in Stage 2 will be extended for up to 2 years post prime, for those subjects 
who consent to this. 
Female subjects in Stage 1 of the study who became pregnant with estimated conception within 28 days 
after vaccination with MVA-BN-Filo or within 3 months after vaccination with Ad26.ZEBOV, children 
born to vaccinated female subjects in Stage 1 who became pregnant with estimated conception within 
28 days after vaccination with MVA-BN-Filo or within 3 months after vaccination with Ad26.ZEBOV 
(unless local regulations have additional requirements for follow up) and subjects enrolled in Stage 2 of 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Approved, Date: 2 October 2018
the study (including female subjects who became pregnant and children born to vaccinated female 
subjects who became pregnant as specified above for Stage 1) may be invited for enrollment into the 
VAC52150EBL3005 study for long-term follow-up of safety and immunogenicity for a total of up to 
60 months after the prime vaccination. Roll-over of subjects in Stage 2 of the study will occur after 
unblinding of VAC52150EBL3001 and will only include subjects who received Ad26.ZEBOV and/or 
MVA-BN-Filo. 
Immunogenicity Assessments
Immunogenicity assessments for humoral immune responses will be performed in all subjects (adults, 
adolescents, and children aged 1 year or older) from Stage 1 and Stage 2. Blood samples will be collected 
as specified in the Time and Events Schedules. Subjects from Stage 1 and Stage 2 will be followed-up for 
immunogenicity until 36 months post prime or 1-year post-third vaccination (if applicable) in Stage 1, 
until 1 year post prime for children and adolescents in Stage 2 and until 1 year post prime or 2 years post 
prime (if applicable) for adults in Stage 2.
SUBJECT POPULATION
The study population will consist of:

Stage 1: approximately 40 healthy subjects aged 18 years or older.

Stage 2: approximately 976 healthy subjects aged 1 year or older. The aim is to enroll approximately 
400 adults and approximately 576 children aged ≥1 year (192 adolescents aged 12 to 17 years 
inclusive, 192 children aged 4 to 11 years inclusive, and 192 young children aged 1 to 3 years 
inclusive). Enrollment will be staggered, starting with the eldest age group. The decision to proceed
to the next age group will be based on an evaluation by the IDMC.
HIV-positive subjects can be enrolled as long as their general condition is good, ie, they are on 
antiretroviral treatment or have no signs or symptoms of immune incompetence, diagnosed on the basis 
of physical examination, medical history, and the investigator’s clinical judgment.
DOSAGE AND ADMINISTRATION
All subjects in Stage 1 and all subjects randomized to the Ad26.ZEBOV/MVA-BN-Filo arms in Stage 2 
will receive the following as a 0.5 mL intramuscular (IM) injection into either deltoid in the upper arm
(or, if needed, in the thigh):

Ad26.ZEBOV: 5x1010 viral particles (vp) on Day 1

MVA-BN-Filo: 1x108 infectious units (Inf U) on Day 57
Subjects in Stage 1 who consent to this will receive a third vaccination using Ad26.ZEBOV at 5x1010 vp 
at least 2 years post prime vaccination.
Subjects in the control arm of Stage 2 will receive the World Health Organization (WHO)-prequalified
Meningococcal Group A, C, W135 and Y conjugate vaccine (MenACWY) as prime on Day 1 and 
placebo as boost on Day 57. The MenACWY vaccine will be administered as a 0.5 mL IM injection into 
either deltoid in the upper arm. Children aged less than 2 years at randomization will receive a third 
vaccination at 3 months post boost with either placebo (Ad26.ZEBOV/MVA-BN-Filo arm) or 
MenACWY (control arm).
Study vaccines in Stage 2 will be prepared by an unblinded pharmacist or qualified staff member with 
primary responsibility for study vaccine preparation and dispensing and who is not involved in any other 
study-related procedures. Subjects will be administered the study vaccines in a masked syringe in a way 
that maintains double-blinding.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Upon completion of the study, sites may offer MenACWY to the Ad26.ZEBOV/MVA-BN-Filo arm and 
the Ad26.ZEBOV/MVA-BN-Filo vaccine (if licensed and/or WHO-prequalified) to the control arm upon 
consultation with the health authorities.
IMMUNOGENICITY EVALUATIONS
The immunogenicity endpoint of the study includes the evaluation of antibody responses. 
Venous blood samples will be collected from all subjects from Stage 1 and Stage 2 to assess humoral 
immune responses to the vaccines.
Depending on assay and/or sample availability any of the following assays might be performed:

EBOV GP ELISA: to determine the binding antibody levels elicited by vaccination. 

VNA: neutralizing antibody reactivity against the EBOV GP defined as the serum titer that is able to 
inhibit viral infection by a certain percentage (IC50; IC80 or IC90). 

ELISA, VNA, and/or PRNT: to explore the binding and/or neutralizing antibody response against the 
adenovirus and/or MVA vector.
SAFETY EVALUATIONS
All safety evaluations (including physical examinations, vital signs, body temperature, and laboratory 
evaluations in Stage 1 and Stage 2) will be performed as specified in the Time and Events Schedules.
The safety and tolerability endpoints are:

Solicited local and systemic adverse events (reactogenicity), collected until 7 days after the prime 
and boost vaccination (Stage 1 and Stage 2) and the third vaccination (Stage 1) as recorded by the 
subjects (or, when appropriate, by a project field worker, a caregiver, surrogate, or the subject's 
legally acceptable representative) in a diary during daily home contacts with a project field worker.

Solicited local and systemic adverse events (reactogenicity), collected until 60 minutes after the 
prime and boost vaccination and until 30 minutes after the third vaccination in all subjects from 
Stage 1, and until 30 minutes after the prime and boost vaccination in all subjects from Stage 2. 

Unsolicited adverse events, collected by the investigator or the clinical designee from signing of the 
ICF onwards until 56 days after the boost vaccination in Stage 1 and then again from the day of the 
third vaccination until 28 days after the third vaccination, and from signing of the ICF onwards until 
28 days after the prime vaccination in Stage 2, and then again until 28 days after the boost 
vaccination. (Note: events that started before the third vaccination but are still present at the time of 
third vaccination should also be recorded).

Serious adverse events, including deaths, and immediate reportable events (IREs) collected in all 
subjects from Stage 1 and 2 from signing of the ICF onwards until the subject’s last study visit.
STATISTICAL METHODS
The primary analysis of immunogenicity and safety in Stage 1 will be performed when all subjects have 
completed the study or have discontinued earlier. In Stage 2, primary analyses will be performed for 
adults (≥18 years) and children (≥1 to 17 years) when these respective groups complete the study or 
subjects have discontinued earlier. One primary analysis for all children is planned, presenting the data by 
age group (12 to 17 years, 4 to 11 years, 1 to 3 years, inclusive). Interim analyses may be performed 
during the study per age group (ie, ≥18 years, 12 to 17 years, 4 to 11 years, 1 to 3 years, inclusive) for the 
purpose of informing future program-related decisions and for regulatory purposes in a timely manner.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Sample Size
Table 1 shows the numbers of subjects planned for safety and immunogenicity by age group for Stage 1 
and Stage 2. 
Table 1:
Number of Subjects Planned per Stage and Population for Safety 
and Immunogenicity Assessments
Safety and Immunogenicity Data
Stage 1
Stage 2
Population Age
(years inclusive)
Ebola vaccinea
Ebola vaccineb
Active controlc
Adults (≥18 years)
40
300
100
12 to 17 years
-
144
48
4 to 11 years
-
144
48
1 to 3 years
-
144
48
Total
40
732
244
a
Prime-boost regimen of Ad26.ZEBOV followed by MVA-BN-Filo (boost vaccination)
and Ad26.ZEBOV (third vaccination).
b
Prime-boost regimen of Ad26.ZEBOV followed by MVA-BN-Filo.
c
The active control will consist of the WHO-prequalified MenACWY vaccine.
For safety, the sample sizes selected indicate that the probability of observing at least 1 (serious) adverse 
event occurring at a rate of 1/10 or more in each group (Stage 1; adults, Stage 2; adults, 12-17 years, 
4-11 years, and 1-3 years) is ≥99%. The probability of observing at least 1 (serious) adverse event 
occurring at a rate of 1/100 is 95% with 300 subjects. The probability of observing at least 1 (serious)
adverse event occurring at a rate of 1/1,000 is 26% with 300 subjects and 52% with 732 subjects. If no 
events are observed during Stage 2 for a specific adverse event, then the Bayesian posterior probability 
that the event rate is below 1/1,000 equals 41% for 144 subjects (ie, the number of children in each age 
group), 56% for 300 subjects (ie, the number of adults), and 77% with 732 subjects when using Jeffreys’ 
prior.
As part of Amendment 5, the number of children in each age group was doubled to compensate for an 
expected higher variability in immunogenicity parameters.
Immunogenicity Analyses
Descriptive statistics (actual values, changes from baseline, if applicable) will be calculated for 
continuous immunologic parameters at all time points analyzed. Geometric mean concentrations and/or
titers and changes together with a corresponding 95% confidence interval will be calculated. Graphical 
representations of changes in immunologic parameters will be prepared, as applicable. Frequency 
tabulations will be calculated for discrete (qualitative) immunologic parameters at all time points and 
response analyses will be performed. Different definitions of immunologic response will be further 
detailed in the statistical analysis plan (SAP).
In addition, a longitudinal data analysis of the immunogenicity response over time will be explored. Least 
square means with their 95% confidence intervals will be calculated from this model. 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Safety Analyses
No formal statistical testing of safety data is planned. Safety analysis will be performed on the safety 
analysis set. Data from Stage 1 will be summarized separately. Safety data from Stage 2 will be shown by 
treatment group (as treated), and by age group.
Safety data will be analyzed descriptively (including 95% confidence intervals, if applicable) for subjects 
receiving control or active vaccine. 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Status: Approved, Date: 2 October 2018
k) Prior to study vaccine administration. 
l)
Prior to study vaccine administration and at the end of the observation period.
m) Polymerase chain reaction (PCR) testing for Ebola will be performed before immunogenicity samples are exported. This can be done on leftovers from the hematology blood 
sample. On visits where no hematology sample is taken, an additional 1.2 mL blood will be drawn for PCR testing (additional volumes counted as part of the immunogenicity 
sample).
n) Subjects who consent to receive the third vaccination will follow this schedule until the Day 540 visit; thereafter, they will follow the next TIME AND EVENTS 
SCHEDULE – Stage 1 Continued (Third Vaccination).
o) Subjects may be contacted approximately 1 month after their last visit to inquire after their general health status.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Status: Approved, Date: 2 October 2018
NOTE: If a subject did not receive study vaccine on the planned day of vaccination, the timings of the next visits post-vaccination will be determined relative to the actual day of 
vaccination.
NOTE: In case of early withdrawal due to an adverse event, the investigator or designee will collect all information relevant to the adverse event and safety of the subject, and 
will follow the subject until resolution of the adverse event or until reaching a clinically stable endpoint. Subjects who wish to withdraw consent will be offered an optional visit 
for safety follow-up (before the formal withdrawal of consent). The subject has the right to refuse.
a)
Informed consent must be provided before the first study-related activity of the third vaccination schedule. Adult subjects (aged 18 years or older at screening) must 
sign an ICF indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study. In case the subject 
cannot read or write, the procedures must be explained and informed consent must be witnessed by a literate third party not involved in the conduct of the study.
b)
For contraindications to receive the third vaccination, refer to Section 10.3.
c)
Visit to a clinic where subject is seen by a study nurse or physician. Subjects will be asked to stay in the clinic for 30 minutes after the third vaccination. The 
observation time may be extended if deemed necessary by the study staff.
d)
Daily home contacts by project field worker to record local and systemic side effects.
e)
A home visit will be arranged in case it is not possible for the subject to visit the clinic. The diary should be completed by the end of the Day 8 post-third visit.
f)
For female subjects of childbearing potential, it should be confirmed that adequate birth control measures consistent with what is available and local standards regarding 
the use of birth control for subjects participating in clinical studies were used from at least 14 days before the third vaccination with a negative urine β-hCG pregnancy 
test immediately prior to vaccine administration.
g)
Prior to study vaccine administration.
h)
Concomitant therapies should be recorded up to 28 days after the third vaccination. Thereafter, they should only be recorded if given in conjunction with serious 
adverse events and IREs.
i)
Does not include body length/height and weight.
j)
During the long-term follow-up, a brief physical examination should only be performed when related to serious adverse events and IREs.
k)
Prior to study vaccine administration and at the end of the observation period.
l)
PCR testing for Ebola will be performed before immunogenicity samples are exported. This can be done on leftovers from the hematology blood sample. On visits 
where no hematology sample is taken, an additional 1.2 mL blood will be drawn for PCR testing (additional volumes counted as part of the immunogenicity sample).
m) Subjects may be contacted approximately 1 month after their last visit to inquire after their general health status.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Status: Approved, Date: 2 October 2018
explained and informed consent must be witnessed by a literate third party not involved in the conduct of the study. If the subject’s age is below the legal cut-off age for 
consent (according to local regulations), the parent/legal guardian will be asked to give consent, and the subject will be informed about the study. Subjects aged 7 years and 
older will be asked to give positive assent. The assent procedure must be witnessed by an adult literate parent/legal guardian/third party not involved in the conduct of the 
study, and documented.
e) The investigator or designee should ensure that all study enrollment criteria have been met at the end of the screening period. If a subject’s clinical status changes (including 
available laboratory results or the receipt of additional medical records) after screening but before Day 1 such that the subject no longer meets all eligibility criteria, then the 
subject will be excluded from participation in the study. For contraindications to receive the boost vaccination, refer to Section 10.3.
f)
Prestudy therapies administered up to 30 days prior to the start of screening must be recorded at screening.
g) The full physical examination includes body length/height and weight for all subjects. The brief physical examination includes body length/height and weight for children 
aged 12 to 24 months prior to the prime and boost vaccination. For details, refer to Section 9.3.2.
h) For children younger than 18 years, the TOU will be administered to the parent or guardian from whom consent is sought. The TOU will be administered after reading but 
before signing the ICF. If both the parent or guardian and the child will be enrolled in the study, the parent/guardian will need to complete the TOU twice (ie, one for the 
parent/guardian and one for the child). In case the parent/guardian consents for multiple children of the same family, the TOU needs to be completed only once, ie, for the 
first child of the family enrolled in the study. In case the TOU information would change while recruiting multiple children of the same family, the TOU should be completed 
again for the first child of the family that was enrolled after the TOU change had occurred.
i)
A third vaccination (MenACWY or placebo) will be administered to children aged less than 2 years. Subject diaries will not be distributed. Children that experience any 
symptoms will be invited to come for an unscheduled visit as needed.
j)
Visit to a clinic or satellite vaccination post where subject is seen by a study nurse or physician. Subjects will be asked to stay in the clinic/vaccination post for 30 minutes 
after the prima and boost vaccination and symptoms of unsolicited and solicited local and systemic adverse events will be documented at the end of the observation period. 
The observation time may be extended if deemed necessary by the study staff. 
k) Daily home contacts by project field worker to record local and systemic side effects.
l)
A home visit could be arranged in case it is not possible for the subject to visit the clinic to ensure the collection of local and systemic reactions. The diary should be 
completed and collected at the Day 8 and Day 8 post-boost visit, respectively.
m) For sexually active female subjects of childbearing potential, it should be confirmed that adequate birth control measures consistent with what is available and the local 
standards regarding the use of birth control for subjects participating in clinical studies were used from at least 14 days before the prime vaccination with a negative urine 
β-hCG pregnancy test at screening and immediately prior to each study vaccine administration.
n) Prior to study vaccine administration.
o) Concomitant therapies should be recorded from screening onwards until 28 days post prime and then again until 28 days post-boost vaccination. At the other time points, it 
should only be recorded if given in conjunction with serious adverse events and IREs.
p) During the long-term follow-up, a brief physical examination should only be performed when related to serious adverse events and IREs.
q) Prior to study vaccine administration and at the end of the observation period.
r)
Only applicable for adults.
s)
PCR testing for Ebola will be performed before immunogenicity samples are exported. This can be done on leftovers from the hematology blood sample. On visits where no 
hematology sample is taken, an additional 1.2 mL blood will be drawn for PCR testing (additional volumes counted as part of the immunogenicity sample).
t)
Subjects may be contacted approximately 1 month after their last visit to inquire after their general health status.

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Status: Approved, Date: 2 October 2018
ABBREVIATIONS
Ad
adenoviral vector (serotype indicated by a number, eg, Ad26)
Ad26.ENVA.01 
Ad26 vector expressing the human immunodeficiency virus type 1, Clade A envelope protein
Ad26.ZEBOV
Ad26 vector expressing the glycoprotein of the Ebola virus Mayinga variant
ALT
alanine aminotransferase
AST
aspartate aminotransferase
β-hCG
β-human chorionic gonadotropin
BMI
body mass index
BN
Bavarian Nordic
CDC
Centers for Disease Control and Prevention
COMAHS
College of Medicine and Allied Health Sciences
CRF
case report form 
EBODAC
Ebola vaccine Deployment, Acceptance & Compliance
EBOV
Ebola virus
eDC
electronic data capture
ELISA
enzyme-linked immunosorbent assay
Env
Envelope
EU
European Union
EVD
Ebola Virus Disease
GCP
Good Clinical Practice
GLP
Good Laboratory Practice
GP
glycoprotein
HIV
human immunodeficiency virus
ICF
informed consent form
ICH
International Council for Harmonisation
IDMC
Independent Data Monitoring Committee
IEC
Independent Ethics Committee
IM
intramuscular
IMI
Innovative Medicines Initiative
Inf U
infectious units
IRB
Institutional Review Board
IRE
immediate reportable event
ITN
insecticide treated bed net
IVRS
Interactive Voice Response System
IWRS
Interactive Web Response System
kb
kilobase
MARV
Marburg virus
MedDRA
Medical Dictionary for Regulatory Activities
MoHS
Ministry of Health and Sanitation
MVA
Modified Vaccinia Ankara
MVA-BN
Modified Vaccinia Ankara - Bavarian Nordic
MVA-BN-Filo
Modified Vaccinia Ankara - Bavarian Nordic-multivalent filovirus vector
NGO
non-governmental organization
NHP
nonhuman primate
NP
nucleoprotein
NSAID
nonsteroidal anti-inflammatory drug
PQC
Product Quality Complaint
PRNT
plaque reduction neutralization test
RBC
red blood cell
RNA
ribonucleic acid
PCR
polymerase chain reaction
SAP
Statistical Analysis Plan
SPC
Summary of Product Characteristics
SUDV
Sudan virus
SUSAR
suspected unexpected serious adverse reaction
TAFV
Tai Forest virus
TCID50
50% tissue culture infective dose

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Status: Approved, Date: 2 October 2018
TOU
test of understanding
UK
United Kingdom
US
United States
VISP
vaccine induced seropositivity
VNA
virus neutralization assay
vp
viral particles
WBC
white blood cell
WHO
World Health Organization
DEFINITIONS OF TERMS
Study vaccine
MVA-BN-Filo or Ad26.ZEBOV or control MenACWY/placebo
Independent study 
vaccine monitor
An unblinded study vaccine 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 9.3.2. 
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.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Status: Approved, Date: 2 October 2018
1.
INTRODUCTION
Janssen Vaccines & Prevention B.V. (formerly known as Crucell Holland B.V., hereafter 
referred to as the sponsor), in collaboration with Bavarian Nordic GmbH, Denmark, and in 
conjunction with the London School of Hygiene & Tropical Medicine and Sierra Leonean MoHS
and COMAHS, and the EBODAC program, is investigating the potential of a prophylactic 
heterologous prime-boost Ebola vaccine regimen that is targeting the EBOV species, which is 
responsible for the Ebola Virus Disease (EVD) outbreak that started in December 2013 in 
Guinea and further spread to a number of other countries in West Africa. The vaccine regimen 
comprises the following 2 candidate Ebola vaccines:
Ad26.ZEBOV (JNJ-61210474-AAA) is a monovalent vaccine expressing the full length Ebola
virus (EBOV, formerly known as Zaire ebolavirus) Mayinga GP. The vaccine is produced in the 
human cell line PER.C6®.
MVA-mBN226B (JNJ-63839880-AAA) (further referred to as MVA-BN-Filo®) is a multivalent 
vaccine expressing the EBOV GP, the SUDV GP, the MARV Musoke GP, and the TAFV NP
(formerly known as Côte d’Ivoire ebolavirus). 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). A brief summary of the nonclinical and clinical information available at the time of 
the protocol writing is provided below.8,9
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.
1.1.
Background
Ebola viruses belong to the Filoviridae family and cause EVD, which can induce severe 
hemorrhagic fever in humans and nonhuman primates (NHPs). Case fatality rates in EVD range 
from 25% to 90% (average: 50%), according to the World Health Organization (WHO).14 These 
viruses are highly prioritized by the United States (US) Government, who has defined them as 
‘Category A’ agents, due to the high mortality rate of infected individuals. Currently, no licensed 
vaccine, treatment or cure exists 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 
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 a RNA-dependent RNA 
polymerase, which is carried into the cell together with the virus.6

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Status: Approved, Date: 2 October 2018
In this Phase 3 study, the sponsor’s adenovirus serotype 26 (Ad26) vector expressing the EBOV 
Mayinga GP (Ad26.ZEBOV) and the Modified Vaccinia Ankara (MVA) - Bavarian Nordic (BN) 
vector with EBOV, SUDV and MARV GP inserts and TAFV NP insert (MVA-BN-Filo) will be 
evaluated as a heterologous prime-boost regimen, in which one study vaccine (Ad26.ZEBOV) is 
used to prime a filovirus-specific immune response and the other study vaccine (MVA-BN-Filo) 
is used to boost the immune response 56 days later. The EBOV GP that is currently circulating in 
West Africa has 97% homology to the EBOV GP used in this vaccine regimen.1
Nonclinical Studies
Immunogenicity and Efficacy
Immunogenicity and efficacy of the vaccine combination Ad26.ZEBOV and MVA-BN-Filo was 
evaluated in an NHP model (ie, Cynomolgus macaques, Macaca fascicularis). The combination 
was assessed in a multivalent filovirus setting in a small number (2 per regimen) of animals and 
the study included heterologous prime-boost regimens of Ad26, serotype 35 (Ad35) and MVA-
BN-Filo vectors expressing different Ebola and Marburg proteins. Full protection from EVD and 
death after wild-type EBOV Kikwit 1995 challenge was obtained with all heterologous 
regimens, including the Ad26 and MVA vaccine regimen. All heterologous prime-boost 
regimens induced comparable immune responses against the EBOV Mayinga GP. Independently 
of the vaccine regimen, a strong boost effect was seen after heterologous prime-boost 
immunization. 
Two additional studies involving more animals have been performed, to strengthen the 
robustness of the nonclinical efficacy data, and also to optimize the prime-boost schedule so as to 
obtain induction of protective immunity as quickly as possible, to specifically respond to the 
EVD outbreak. Complete survival in animals was observed with 8-week heterologous regimens 
employing Ad26.ZEBOV as prime and MVA-BN-Filo as boost, whereas a high dose of MVA-
BN-Filo in these regimens was associated with complete protection against Ebola virus disease. 
Partial protection was observed with both MVA-BN-Filo as a prime immunization and a shorter 
prime/boost interval.
Toxicology
A Good Laboratory Practice (GLP)-compliant, repeated-dose toxicity study was conducted in 
rabbits with prime-boost combinations of Ad26.ZEBOV and MVA-BN-Filo. The different dose 
regimens were well tolerated when administered twice by IM injection with a 14-day interval 
period. All vaccine dosing regimens resulted in detectable ZEBOV GP-specific antibody titers. 
No significant toxicological effects (no adverse effects) were observed. The immune response 
was associated with transient increases in C-reactive protein, fibrinogen, and globulin, decreases 
in hematocrit and hemoglobin, and microscopic findings in draining iliac lymph nodes, spleen 
and at the injection sites. The findings were noted to be recovering over a 2-week treatment-free 
period and were considered to reflect a physiological response associated with vaccination.
There were no effects noted that were considered to be adverse.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Status: Approved, Date: 2 October 2018
In an embryofetal and pre- and postnatal development study in female rabbits, there was no 
maternal or developmental toxicity following maternal exposure to the vaccine regimens during 
the premating and gestation period. All vaccine regimens elicited detectable EBOV GP-specific 
maternal antibody titers that were transferred to the fetuses.
Biodistribution
Single-dose biodistribution studies in rabbits were performed using the MVA-BN vector or the 
Ad26 vector in combination with another insert (Ad26.ENVA.01: an experimental, prophylactic 
Ad26 vector expressing the human immunodeficiency virus [HIV] type 1, Clade A envelope 
[Env] protein). MVA-BN distributed to the skin, muscle, blood, spleen, lung, liver, and pooled 
lymph nodes and was rapidly cleared (within 48 hours following vaccination). Ad26.ENVA.01 
was primarily localized in the injection site muscle, the regional lymph nodes and the spleen. 
Three months after the single IM injection of Ad26.ENVA.01, the vaccine was cleared from 
most of the examined tissues. As biodistribution is dependent on the vector platform (MVA or 
Ad26) and not on the insert, it can be assumed that recombinant MVA-BN-Filo or Ad26.ZEBOV 
is distributed in the same way as the MVA-BN vector or Ad26.ENVA.01 vector, respectively.
Clinical Studies
The safety, tolerability, and immunogenicity of the Ad26.ZEBOV vaccine are being assessed in 
the ongoing Phase 1 (VAC52150EBL1001, VAC52150EBL1002, VAC52150EBL1003, 
VAC52150EBL1004 and VAC52150EBL1005), Phase 2 (VAC52150EBL2001) and Phase 3 
clinical studies (VAC52150EBL3001, VAC52150EBL3002 and VAC52150EBL3003), where 
monovalent Ad26.ZEBOV vaccine and multivalent MVA-BN-Filo vaccine are combined in 
homologous or heterologous prime-boost regimens in which each vector is used to prime a 
filovirus-specific immune response followed by a boost immunization with the same or the other 
vector 2 to 12 weeks later. To date, 1,176 healthy adult subjects have been enrolled in these 
9 ongoing studies. Two additional Phase 1 studies investigating MVA-BN-Filo are also ongoing 
(EBL01 and CVD-Mali Ebola Vaccine #1000). Refer to the latest versions of the Ad26.ZEBOV 
and MVA BN Filo Investigator’s Brochures and Addenda (if applicable) for more details.8,9
Limited data from the ongoing Phase 1 studies with Ad26.ZEBOV and MVA-BN-Filo are 
available. To date, no deaths and no other serious adverse events at least possibly related to study 
vaccine were reported.
VAC52150EBL1001, a first-in-human study, is a randomized, placebo-controlled, observer-
blind study in healthy adults evaluating the safety, tolerability and immunogenicity of 4 regimens 
using MVA BN-Filo at a dose of 1x108 50% tissue culture infective dose (TCID50) and 
Ad26.ZEBOV at a dose of 5x1010 viral particles (vp): 2 regimens with MVA BN-Filo as prime 
and Ad26.ZEBOV as boost at a 28- or 56-day interval, and 2 regimens with Ad26.ZEBOV as 
prime and MVA-BN-Filo as boost at a 28- or 56-day interval. A fifth regimen, with 
Ad26.ZEBOV at a dose of 5x1010 vp as prime, and MVA-BN-Filo at a dose of 1x108 TCID50 at a 
14-day interval has been evaluated in an open-label, uncontrolled, substudy in healthy adults. 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Status: Approved, Date: 2 October 2018
VAC52150EBL1001 has enrolled 87 subjects and primary analysis data for safety and 
immunogenicity are available for 85 subjects (performed when all subjects had completed their 
21-day post-boost visit or discontinued earlier). In both the main study and substudy, no deaths 
or adverse events of special interest have been reported. Two subjects in the substudy who 
experienced grade 3 neutropenia did not receive the boost vaccination as they met criteria for 
contraindications to administration of the boost (specified in the protocol), but continued 
scheduled assessments as planned. There were no serious adverse events related to the study 
vaccines.
In the main study, the most frequent solicited local adverse event was injection site pain. The 
most common solicited systemic adverse events were fatigue, headache and myalgia. 
In the main study, grade 3 solicited local adverse events occurred in 3 subjects (injection site 
pain and injection site swelling in 1 subject each, injection site erythema in 2 subjects). These 
events occurred after Ad26.ZEBOV vaccination. Grade 3 solicited systemic events were also 
reported in 3 subjects (nausea and headache in 2 subjects each, myalgia and fatigue in 1 subject 
each). All these events occurred after Ad26.ZEBOV, except fatigue which occurred after 
placebo. The systemic events after Ad26.ZEBOV were considered to be at least possibly related 
to vaccination by the investigator. 
In the substudy, no subjects experienced grade 3 solicited local events. Grade 3 solicited 
systemic events occurred in 3 subjects after Ad26.ZEBOV (chills and fatigue in 3 subjects each, 
headache in 2 subjects, pyrexia and nausea in 1 subject each). All were considered to be at least 
possibly related to vaccination by the investigator. No grade 3 solicited systemic events were 
reported after MVA BN-Filo. 
Overall, the reported adverse events following vaccination were mild in the majority of subjects, 
transient in nature, and resolved without sequelae. These findings are consistent with the safety 
profiles observed for similar vaccines. The safety profile of the individual vaccines when used as 
prime was comparable to that when used as boost. 
Both vaccination sequences tested in the main study (ie, Ad26.ZEBOV prime followed by 
MVA-BN-Filo boost and MVA-BN-Filo prime followed by Ad26.ZEBOV boost) were highly 
immunogenic and induced considerable humoral and cellular immune responses. Extending the 
interval between the prime and boost led to increased antibody responses (magnitude at a 56-day 
prime-boost interval was about 1.8 times higher than at a 28 day prime-boost interval), while the 
effect was less pronounced or the reverse for T cell responses. The induced immune responses 
were functional, as demonstrated by the neutralizing activity of the antibody responses in all 
subjects. The composition of the induced T cell response was favorable, with a high percentage 
of polyfunctional T cells, which generally are thought to play a role in immunological memory 
and effector functions.
Study VAC52150EBL1002 completed enrollment of 92 subjects; the blinded phase of the study 
is ongoing. No serious adverse events related to study vaccine have been reported and no safety 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Status: Approved, Date: 2 October 2018
issues have been identified to date. Safety data generated with the 2 vaccines with different 
inserts are provided below.
Safety Profile of Ad26.ZEBOV
Ad26.ZEBOV is a monovalent, replication-incompetent Ad26-based vaccine. Only limited 
clinical data are available for Ad26.ZEBOV. However, adenovirus vaccine programs with other 
gene inserts have revealed no significant safety issues.
Safety Profile of MVA-BN 
MVA-BN is a further attenuated version of the MVA virus, which in itself is a highly attenuated 
strain of the poxvirus Chorioallantois Vaccinia Virus Ankara. MVA-BN induces strong cellular 
activity as well as a humoral (antibody) immune response and has demonstrated an ability to 
stimulate a response even in individuals with pre-existing immunity against Vaccinia. One of the 
advantages of MVA-BN is the virus’ inability to replicate in a vaccinated individual. The 
replication cycle is blocked at a very late stage, which ensures that new viruses are not generated 
and released. This means that the virus cannot spread in the vaccinated person and none of the 
serious side effects normally associated with replicating Vaccinia viruses have been seen with 
MVA-BN. 
MVA-BN (MVA-BN®, trade name IMVAMUNE® outside the European Union [EU], invented 
name IMVANEX® in the EU) has received marketing authorization in the EU for active 
immunization against smallpox in adults and in Canada for persons 18 years of age and older 
who have a contraindication to the first or second generation smallpox vaccines including 
individuals with immune deficiencies and skin disorders.7 A Phase 3 clinical study has been 
performed in the US (POX-MVA-013). Results of completed and ongoing clinical studies of 
MVA-BN-based vaccines in more than 8,100 individuals, including elderly subjects (up to age of 
80 years), children, and subjects in whom traditional replicating vaccines are contraindicated (eg, 
individuals with HIV infection or diagnosed with atopic dermatitis), have shown that the 
platform displays high immunogenicity and a favorable safety profile. Across all clinical studies, 
no trends for unexpected or serious adverse reactions due to the product were detected. 
MVA-BN-Filo is currently also being used in 2 Phase 1 studies in the UK and in Mali (EBL01 
and CVD-Mali Ebola Vaccine #1000). In these studies, subjects receive prime vaccination with 
the monovalent chimpanzee adenovirus vectored cAd3-EBO Z vaccine, followed by MVA-BN-
Filo as a booster. No safety concerns have arisen from these studies.
Safety information was pooled from the first 2 studies of MVA-BN-Filo (VAC52150EBL1001 
and VAC52150EBL1002). In general, MVA-BN-Filo has been shown to be well tolerated.9
Three fifths of the subjects reported at least one local site reaction (injection site pain, 
tenderness, warmth, redness, swelling and/or itching) following administration of MVA-BN-
Filo; mostly of mild severity. The most common reported local site reaction was pain at the 
injection site. All the local reactions resolved to normal without any lasting effects.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Status: Approved, Date: 2 October 2018
At least one general symptom was reported in two fifths of the subjects following MVA-BN-Filo 
administration. The most common general symptoms were fatigue, headache, myalgia (muscle 
pain) and nausea. All general symptoms were transient and resolved without lasting effects.  
Changes in laboratory tests were reported following MVA-BN-Filo administration which 
included hypokalemia and decreased numbers of neutrophils (neutropenia). Both changes in 
laboratory tests were seen in similar numbers of participants following MVA-BN-Filo and the 
dummy (placebo) vaccine. Less frequently, events of decreased hemoglobin levels were 
reported. The changes in laboratory tests were not associated with any complaints or symptoms.
Extensive nonclinical studies support the safety profile of the MVA-BN strain.11,12
Relevant Safety Information from Ongoing VAC52150 Studies
One subject in the study VAC52150EBL2001 experienced a serious and very rare condition 
called “Miller Fisher syndrome”. This condition consists of double vision, pain on moving the 
eye, and difficulty with balance while walking. Miller Fisher syndrome most commonly occurs 
following a recent infection. The subject experienced these symptoms about a week after 
suffering from a common cold and fever. The event happened about a month after boost 
vaccination with either MVA-BN-Filo or placebo. This subject had to go to the hospital for 
treatment and has recovered. After an extensive investigation, the event has been considered to 
be doubtfully related to vaccine and most likely related to the previous common cold.
In the ongoing clinical studies with more than 2,000 participants, there have been a few reports 
of mild to moderate tingling especially in the hands and feet or a sensation of mild to moderate 
muscle weakness in subjects vaccinated with Ad26.ZEBOV or placebo. These symptoms have 
been observed to last no more than 24 to 48 hours in the majority of cases but can last for several 
weeks before going away on their own. These types of symptoms have also been reported 
following administration of other licensed vaccines and following acute viral infections of 
various types. One serious case of probable peripheral sensory neuropathy of moderate severity 
has occurred and has been ongoing for several months, interfering with some of the subject’s
daily activities.
Viral Shedding 
Viral shedding information is available from 6 clinical studies with adenovirus vectored vaccines 
against HIV type 1 (using Ad26 and Ad35: Ad26.ENVA.01 and Ad35.ENV) and Mycobacterium
tuberculosis (using Ad35: AERAS-402). Viral shedding was not observed in any of these clinical 
studies. In a clinical study evaluating viral shedding of Ad26.ENVA.01 and Ad35.ENV 
(Study IPCAVD-004), all cultures from oropharyngeal swabs and urine were negative for 
adenovirus; in 5 clinical studies evaluating viral shedding of AERAS-402 (Studies C-001-402, 
C-003-402, C-008-402, C-009-402, C-017-402), no shedding of AERAS-402 was seen in any of 
the urine or throat cultures.8

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Status: Approved, Date: 2 October 2018
MVA-BN-Filo is an attenuated recombinant MVA incapable of replication in human cells with a 
block in the late stage of virus replication. In human cells, upon infection, viral genes are 
expressed, but no infectious progeny virus is produced. Given the inability of virus assembly and 
very limited host range of the vector, no viral shedding studies have been performed.
1.2.
Risk Benefit Section
1.2.1.
Known Benefits
Ad26.ZEBOV and MVA-BN-Filo 
The clinical benefit of prime-boost combinations of Ad26.ZEBOV and MVA-BN-Filo is to be 
established.
MenACWY 
To offer clinical benefit to subjects in the control group in Stage 2, 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 24 to 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.15,16
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.
1.2.2.
Potential Benefits
Ad26.ZEBOV and MVA-BN-Filo 
Subjects may benefit from clinical testing and physical examination; others may benefit from 
knowledge gained in this study that may aid in the development of an Ebola vaccine.
If the study vaccines indicate protection, then the participants may benefit from potential 
protection against EVD.
1.2.3.
Known Risks
Ad26.ZEBOV and MVA-BN-Filo 
To date, there are only limited data from the Phase 1 studies with Ad26.ZEBOV and MVA-BN-
Filo available. However, Ad26- and Ad35-based vaccines with other gene inserts have been
administered to a limited number of human volunteers in clinical studies. These other vaccines 
mainly elicited some local and systemic solicited reactions, as expected with injectable vaccines, 
and no serious safety concerns were recorded in study participants. Across clinical studies, 
MVA-BN-based vaccines have been administered to more than 8,100 individuals and no trends 
for unexpected or serious adverse reactions due to the product were detected. For details, see the 
safety data presented in Section 1.1.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Status: Approved, Date: 2 October 2018
MenACWY 
Very common side effects (affecting ≥1 in 10 people) of MenACWY vaccination include pain, 
redness 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. 
1.2.4.
Potential Risks
The following potential risks for Ad26.ZEBOV and MVA-BN-Filo will be monitored during the 
study and are specified in the protocol.
Vaccine Induced Seropositivity
The potential of a study participant becoming PCR-positive after vaccination is being assessed in 
the ongoing Phase 1 US study VAC52150EBL1002. The risk for false positives is low and 
expected to decrease rapidly over time after administration of Ad26.ZEBOV/MVA-BN-Filo. An 
account of procedures followed when a PCR test is performed for the evaluation of fever, is 
given in Section 9.1.6.
In general, uninfected subjects who participate 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.
Risk of Myo/Pericarditis
While replicating smallpox vaccines have been associated with an increased risk of developing
myo/pericarditis,10 this has not been observed with MVA-BN and is not expected with this 
highly attenuated, non-replicating vaccine. Based on observations with first- and second-
generation replication-competent smallpox vaccines, particular attention has been placed on the 
monitoring for cardiac signs and symptoms in all clinical studies using MVA-BN. Despite the 
close cardiac monitoring, no event indicating a symptomatic case of myo/pericarditis has been 
observed in any completed MVA-BN study. There has been 1 case of chest pain that might be 
indicative of pericarditis (consisting of chest pain only with no other cardiac findings suggestive 
of pericarditis) with previous MVA use, although this diagnosis was not finally confirmed and 
the patient fully recovered. In a review of prospective surveillances for cardiac adverse events in 
6 different clinical studies in 382 subjects receiving MVA vaccines, only 1 subject (0.3%) met 
the criteria for vaccine-induced myocarditis and eventually the subject was found to suffer from 
exercise-induced palpitations. Self-limited mild elevations in troponin I were recorded in 
3 (0.8%) subjects without evidence of myo/pericarditis.4 Based on the current exposure data in 
more than 8,100 subjects vaccinated with MVA-BN and other MVA-BN recombinant products, 
the safety profile of MVA-BN has shown to be comparable with other licensed, live attenuated 
vaccines.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Status: Approved, Date: 2 October 2018
Risks Related to Vaccines
Subjects may exhibit general signs and symptoms associated with administration of a vaccine, 
including fatigue, nausea, headache, vomiting, myalgia, rash, arthralgia, general itching, fever, 
and chills. In addition, subjects may experience local (injection site) reactions such as redness of 
skin, swelling/induration, pain/tenderness, and/or itching at the injection site. These events will 
be monitored, but are generally short-term and do not require treatment. 
Fear of injection might result in a vasovagal response, hyperventilation, and in children 
sometimes in vomiting, breath-holding and rarely convulsions. 
Subjects may have an allergic reaction to the vaccination. An allergic reaction may cause a rash, 
hives or even difficulty breathing (anaphylaxis). Severe reactions are rare. Medications will be 
available in the clinic or vaccination post to treat severe allergic reactions for subjects in Stage 1 
and Stage 2. 
Risks from Blood Draws
Blood draws may cause pain, bruising, bleeding, and, rarely, infection at the site where the blood 
is taken.
Pregnancy and Birth Control
The effect of the vaccines on a fetus or nursing baby is unknown, as well as the effect on semen.
For sexually active female subjects of childbearing potential, it should be confirmed that 
adequate birth control measures consistent with what is available and the local standards
regarding the use of birth control for subjects participating in clinical studies were used from at 
least 14 days before the prime vaccination with a negative urine β-human chorionic gonadotropin 
(β-hCG) pregnancy test at screening and immediately prior to each study vaccination (including 
a late boost vaccination where applicable for subjects affected by a study pause). All male and 
female subjects, except for female subjects of non-childbearing potential, will be asked to use 
adequate birth control for sexual intercourse until at least 3 months after the prime vaccination or 
up to 28 days after the boost vaccination (whichever takes longer). Subjects receiving the third 
vaccination in Stage 1 will be asked to use adequate birth control for sexual intercourse from at 
least 14 days prior and until 3 months after the third vaccination. 
Pregnancy outcomes from all female subjects who became pregnant during the study until up to 
28 days after the boost vaccination or 3 months after the prime vaccination (whichever is longer) 
as well as from those who became pregnant between at least 14 days before until up to 3 months 
after the third vaccination may be collected in the current study or in the VAC52150EBL3005
long-term follow-up study for subjects who consent to this.
Children born to these female subjects may be enrolled in the VAC52150EBL3005 study and 
followed for 5 years if the parent consents to this.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Status: Approved, Date: 2 October 2018
1.2.5.
Unknown Risks
There are no clinical data on the use of Ad26.ZEBOV and MVA-BN-Filo in:

Pediatric subjects (<18 years)

Pregnant or nursing women

Elderly subjects (>50 years)

Immunocompromised patients (including those with HIV infection)
For more information on the unknown risks of MenACWY vaccines, refer to the most recent 
versions of the applicable vaccine prescribing information.
There may be other serious risks that are not known.
1.2.6.
Overall Benefit/Risk Assessment
Based on the available data and proposed safety measures, the overall risk/benefit assessment for 
this clinical study is considered acceptable for the following reasons:

Preliminary safety data from the ongoing Phase 1 studies have shown no significant safety 
concerns to date. Also, safety data generated with the 2 vaccines with different inserts have 
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.

An IDMC will be established to monitor safety data on an ongoing basis to ensure the 
continuing safety of the subjects enrolled in this study. Details are provided in Section 3.1
and Section 11.7. 

Safety will be closely monitored throughout Stage 1 and Stage 2 of the study. Several safety 
measures are included in this protocol to minimize the potential risk to subjects, including 
the following:

The safety evaluations in Stage 1 and Stage 2 described in Section 9.3.2. The 
neuroinflammatory disorders listed in Section 12.1.1 should be categorized as IREs and 
should be reported to the sponsor as described in Section 12.3.3.

The study will commence with vaccination of a group of approximately 40 adult 
subjects (≥18 years of age) in Stage 1. Approximately 976 subjects, including 
approximately 400 adults and approximately 576 children ≥1 year of age and 
adolescents, will be randomized in a 3:1 ratio to receive the Ad26.ZEBOV/MVA-BN-
Filo prime-boost regimen or an active control vaccine and placebo in Stage 2. Subjects 
in Stage 2 will be enrolled in 4 age strata, starting with the eldest age group. A safety 
review by the IDMC in each of the older age groups will be required before a younger
age group can be enrolled. Subjects in Stage 2 will be followed-up for safety until 
12 months (children and adolescents) or 24 months (adults) after the prime vaccination.
Subjects in Stage 2 will be eligible for roll-over into the Study VAC52150EBL3005 for 
long-term safety and immunogenicity follow-up up to 60 months post-prime. Subjects 
in Stage 1 will be followed-up for safety and immunogenicity until 36 months after the 
prime vaccination, or until 1 year after the third vaccination (if applicable).

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Status: Approved, Date: 2 October 2018
1.3.
Overall Rationale for the Study
In nonclinical studies in the Cynomolgus macaque model, heterologous prime-boost regimens of 
a multivalent mixture of Ad26 vectors (each expressing EBOV Mayinga, SUDV or MARV GP) 
and MVA-BN-Filo provided complete protection against the highly pathogenic wild-type EBOV 
Kikwit 1995 variant (report pending).
In humans, both Ad26- and MVA-based vaccines containing various antigenic inserts have been 
shown to be safe and immunogenic (see also Section 1.1). To date, more than 230 subjects have
received the sponsor’s Ad26-based vaccines in completed clinical studies with Ad26.ZEBOV
(based on the adenoviral vaccine safety database report [dated 20 March 2015]). Up to 
28 October 2015, 227 subjects received Ad26.ZEBOV in ongoing studies. The MVA-BN 
platform is the basis of the non-replicating smallpox vaccine registered in Canada and Europe, 
and has been safely used in more than 7,600 humans.9 Furthermore, limited safety data from the 
ongoing Phase 1 studies have shown no safety concerns to date. 
The unprecedented size and scale of the EVD outbreak that started in December 2013 in Guinea 
and subsequently spread to Sierra Leone and Liberia, led to the outbreak being declared a public
health emergency of international concern in August 2014 by the WHO. This study is one of a 
series of studies to evaluate the heterologous combination of Ad26.ZEBOV and MVA-BN-Filo 
as a possible vaccine regimen to prevent EVD.
In this Phase 3 study, Ad26.ZEBOV and MVA-BN-Filo will be evaluated as a heterologous 
prime-boost regimen, in which one study vaccine (Ad26.ZEBOV) is used to prime a filovirus-
specific immune response and the other study vaccine (MVA-BN-Filo) is used to boost the 
immune response 56 days later, to provide long-lasting protection against infection with EVD. In 
Stage 1, a third vaccination (Ad26.ZEBOV) will be administered at least 2 years post prime. The 
EBOV GP that is currently circulating in West Africa has 97% homology to the EBOV GP used 
in this vaccine regimen.
The MVA-BN-Filo dose that will be used in the present study is expressed as 1x108 Inf U. This 
dose corresponds to the dose of 1x108 TCID50 being used in the current Phase 1 studies.
The study protocol will be implemented in conjunction with the London School of Hygiene & 
Tropical Medicine, the MoHS, the COMAHS, and the EBODAC program. The MoHS and 
COMAHS will partner the London School of Hygiene & Tropical Medicine in all aspects of the 
implementation of the study, and particularly with regard to recruitment of clinical and para-
medical staff, training, clinical management, and surveillance. The MoHS will also provide 
referral facilities for all stages of the study. The study surveillance staff will work closely with 
district and national surveillance system to monitor EVD cases and background morbidity and 
mortality. GOAL is supporting the study in logistics, construction, supply and recruitment of 
non-clinical staff.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
55
Status: Approved, Date: 2 October 2018
2.
OBJECTIVES AND HYPOTHESIS
2.1.
Objectives
The primary objective of Stage 1 is:

To evaluate the safety of a heterologous prime-boost regimen utilizing Ad26.ZEBOV and 
MVA-BN-Filo given at a 56-day interval.
The secondary objective of Stage 1 is:

To assess humoral immune responses to a heterologous prime-boost regimen utilizing 
Ad26.ZEBOV and MVA-BN-Filo as measured by an enzyme-linked immunosorbent assay 
(ELISA) at 21 days post-boost vaccination.

To assess the safety and tolerability of a third vaccination using Ad26.ZEBOV administered 
at least 2 years post prime.
The exploratory objectives of Stage 1 are:

To assess humoral immune responses to a heterologous prime-boost regimen utilizing 
Ad26.ZEBOV and MVA-BN-Filo as measured by ELISA at other relevant time points.

To assess neutralizing antibody responses directed against EBOV GP induced by the 
heterologous prime-boost regimen as measured by a virus neutralization assay (VNA) 
depending on sample and assay availability.

To assess antibody responses directed against the Ad26 and/or MVA vector as measured by 
ELISA, VNA, and/or plaque reduction neutralization test (PRNT) depending on sample and 
assay availability.

To assess humoral immune responses to a heterologous prime-boost regimen utilizing
Ad26.ZEBOV and MVA-BN-Filo as measured by ELISA following a third vaccination 
using Ad26.ZEBOV at 2 years post prime. 
The primary objective of Stage 2 is:

To evaluate the safety of a heterologous prime-boost regimen utilizing Ad26.ZEBOV and 
MVA-BN-Filo given at a 56-day interval compared to an active control vaccine.
The secondary objective of Stage 2 is:

To assess humoral immune responses to a heterologous prime-boost regimen utilizing 
Ad26.ZEBOV and MVA-BN-Filo as measured by an ELISA at 21 days post-boost
vaccination.
The exploratory objectives of Stage 2 are:

To assess humoral immune responses to a heterologous prime-boost regimen utilizing 
Ad26.ZEBOV and MVA-BN-Filo as measured by ELISA at other relevant time points. 

To assess neutralizing antibody responses directed against EBOV GP induced by the 
heterologous prime-boost regimen as measured by VNA depending on sample and assay 
availability. 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
56
Status: Approved, Date: 2 October 2018

To assess antibody responses directed against the Ad26 and/or MVA vector as measured by 
ELISA, VNA, and/or PRNT depending on sample and assay availability.
2.2.
Hypothesis
As this study is designed to provide descriptive information regarding safety and 
immunogenicity without formal treatment comparisons, no formal statistical hypothesis testing is 
planned.
3.
STUDY DESIGN AND RATIONALE
3.1.
Overview of Study Design
This is a staged Phase 3 study with an open-label uncontrolled stage (Stage 1) and a double-
blinded controlled stage (Stage 2) to evaluate the immunogenicity and safety of a heterologous 
prime-boost regimen where Ad26.ZEBOV at a dose of 5x1010 vp will be used to prime a 
filovirus-specific immune response and MVA-BN-Filo at a dose of 1x108 Inf U will be used to 
boost the immune response 56 days later. In Stage 1, a third vaccination using Ad26.ZEBOV
will be administered at least 2 years post prime to subjects who consent to this.
The study will be conducted as follows:

Stage 1: The study will commence with vaccination of a group of approximately 40 adult 
subjects aged 18 years or older. The objective of this initial stage of the study is to evaluate 
the safety and immunogenicity of the prime-boost regimen in the adult Sierra Leonean 
population.

Stage 2: Approximately 976 subjects aged 1 year or older will be individually randomized in 
a 3:1 ratio to receive the Ad26.ZEBOV/MVA-BN-Filo prime-boost regimen or an active
control vaccine and placebo. The aim is to enroll approximately 400 adults (aged 18 years or 
older) and approximately 576 children aged ≥1 year (with about 192 children in each of the 
3 age groups [ie, 12 to 17 years, 4 to 11 years, and 1 to 3 years, inclusive]). Enrollment will 
be staggered, starting with the eldest age group. The decision to proceed to the next age 
group will be based on an evaluation by the IDMC (for details see Section 11.7). 
Randomization will be stratified by age group.
Within each age group of Stage 2, study-site personnel (except for those with primary 
responsibility for study vaccine preparation and dispensing), sponsor personnel and subjects will 
be blinded to the study vaccine until all subjects in that age group have completed at least the 
6 month post-boost visit or discontinued earlier and the database has been locked for that age 
group. Should an interim analysis be performed prior to the 6 months post-boost visit of the last 
subject in a given age group, only those involved in the analysis and decision making will be
unblinded.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Status: Approved, Date: 2 October 2018
An IDMC will be commissioned for this study. The IDMC will review all available 7-day post-
prime safety data (including clinical laboratory results) before the first subject of the current 
cohort receives the boost:
In Stage 1 to determine whether:

the boost vaccination in Stage 1 can be initiated, and

the prime vaccination in Stage 2 (subjects aged 12 to 17 years inclusive) can be 
initiated.

In Stage 2 (subjects aged 12 to 17 years inclusive) to determine whether:

the boost vaccination of subjects aged 12 to 17 years inclusive can be initiated, and

the prime vaccination of subjects aged 4 to 11 years inclusive can be initiated.

In Stage 2 (subjects aged 4 to 11 years inclusive) to determine whether:

the boost vaccination of subjects aged 4 to 11 years inclusive can be initiated, and

the prime vaccination of subjects aged 1 to 3 years inclusive can be initiated.

In Stage 2 (subjects aged 1 to 3 years inclusive) to determine whether:

the boost vaccination of subjects aged 1 to 3 years inclusive can be initiated.
The IDMC will also review all cumulative safety data including the 7-day post-boost safety data 
(including clinical laboratory results) to determine if the boost vaccination in the next stage 
and/or next age group can be given. An IDMC meeting will therefore take place with all 
available data (also including the 7-day post-prime safety data within that age group) before 
boost vaccination will be administered.
A schematic presentation of the IDMC schedule is provided in Attachment 1.
The IDMC will also assess on an ongoing basis the Stage 1 and Stage 2 data as well as data 
emerging from Phase 1 and 2 studies and the status of the epidemic.
While Stage 2 of this study was enrolling, the sponsor halted all vaccinations in the clinical 
program due to the occurrence of a serious and very rare condition, Miller Fisher syndrome, 
reported in study VAC52150EBL2001, as well as following reports of mild transient paresthesia 
in the same study, until a revised ICF was prepared and approval to restart the current study was 
granted by all relevant authorities. This interruption in dosing affected 98 consented subjects in 
the current study, who had only received the prime vaccination. When approval was granted to 
restart the study under Amendment 3, a late boost vaccination was offered to those subjects who 
had only received the prime vaccination, unless participants had withdrawn from the study or 
were not eligible to receive the boost. Vaccinated subjects will follow the same post-boost 
vaccination schedule as those subjects unaffected by the pause. Subjects who refuse or are not 
eligible to receive the late boost will be encouraged to remain in the study to be followed for 
safety and immunogenicity.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
58
Status: Approved, Date: 2 October 2018
As part of Amendment 4 for this study, Stage 1 was extended for 2 years beyond Day 360 post 
prime for follow-up of safety and immunogenicity. As part of Amendment 5, subjects in Stage 1 
who consent to this will receive a third vaccination (Ad26.ZEBOV) at least 2 years post prime
vaccination. The follow-up period for adult subjects in Stage 2 will be extended for up to 2 years 
post prime, for those subjects who consent to this. 
Female subjects in Stage 1 of the study who became pregnant with estimated conception within 
28 days after vaccination with MVA-BN-Filo or within 3 months after vaccination with 
Ad26.ZEBOV, children born to vaccinated female subjects in Stage 1 who became pregnant with 
estimated conception within 28 days after vaccination with MVA-BN-Filo or within 3 months 
after vaccination with Ad26.ZEBOV (unless local regulations have additional requirements for 
follow up) and subjects enrolled in Stage 2 of the study (including female subjects who became 
pregnant and children born to vaccinated female subjects who became pregnant as specified 
above for Stage 1) may be invited for enrollment into the VAC52150EBL3005 study for long-
term follow-up of safety and immunogenicity for a total of up to 60 months after the prime 
vaccination. Roll-over of subjects in Stage 2 of the study will occur after unblinding of 
VAC52150EBL3001 and will only include subjects who received Ad26.ZEBOV and/or MVA-
BN-Filo. 
Immunogenicity Assessments
Immunogenicity assessments for humoral immune responses will be performed in all subjects 
(adults, adolescents, and children aged 1 year or older) from Stage 1 and Stage 2. Blood samples 
will be collected as specified in the Time and Events Schedules. The amount of blood taken from 
children will be limited (see Section 9.1.1). Subjects from Stage 1 and Stage 2 will be followed-
up for immunogenicity until 36 months post prime or 1-year post-third vaccination (if 
applicable) in Stage 1, until 1 year post prime for children and adolescents in Stage 2 and until 
1 year post prime or 2 years post prime (if applicable) for adults in Stage 2.
3.2.
Study Design Rationale
The primary endpoint of Stage 1 and Stage 2 is safety and the secondary endpoint of Stage 1 and 
Stage 2 is immunogenicity. 
Stage 1 
Stage 1 of the study is designed to evaluate the prime-boost regimen (Ad26.ZEBOV/MVA-BN-
Filo/Ad26.ZEBOV) in the adult Sierra Leonean population. 
Immunogenicity data from a Phase 1 study
of the monovalent vaccine program 
(VAC52150EBL1002) demonstrated stability of the binding antibody response out to one year 
following prime-boost regimens with Ad26.ZEBOV/MVA-BN-Filo (or the reverse). A third 
vaccination using Ad26.ZEBOV at 5x1010 vp was given at the one-year time point leading to a 
marked and rapid increase in the binding antibody responses within 7 days (at least 10-fold). The 
marked and rapid rise was generally independent of the antecedent prime-boost regimen. The 
profile of the antibody response strongly suggests that robust anamnestic responses can be 
induced after re-exposure to an EBOV antigen, in this case mimicked by a third vaccination.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Status: Approved, Date: 2 October 2018
Administration of a third vaccination using Ad26.ZEBOV at least 2 year post prime for subjects 
in Stage 1 will extend the findings to an African population.
Stage 2 
Stage 2 will evaluate the prime-boost regimen across different age groups including children, 
using age de-escalation. Stage 2 will be an individually randomized, double-blinded, active-
controlled study. Randomization will be used in Stage 2 to minimize bias in the assignment of 
subjects to study arms (Ad26.ZEBOV/MVA-BN-Filo prime-boost regimen or control), to 
increase the likelihood that known and unknown subject attributes (eg, demographic and baseline 
characteristics) are evenly balanced across arms, and to enhance the validity of possible 
statistical comparisons across arms. 
Control recipients are included for blinding purposes and safety analyses, and will provide 
control specimens for immunogenicity assays. The nature of the study vaccine 
(Ad26.ZEBOV/MVA-BN-Filo prime-boost regimen versus control) will be blinded to reduce 
potential bias during data collection and evaluation of clinical safety endpoints. Blinding will be 
guaranteed by preparation of study vaccine by unblinded qualified study-site personnel not 
involved in any other study-related procedures, and by the administration of vaccine in a masked 
syringe in a way that maintains double-blinding.
4.
SUBJECT POPULATION
The study population will consist of:

Stage 1: approximately 40 healthy subjects aged 18 years or older.

Stage 2: approximately 976 healthy subjects aged 1 year or older. The aim is to enroll 
approximately 400 adults (aged 18 years or older) and approximately 576 children aged ≥1 year
(192 adolescents aged 12 to 17 years inclusive, 192 children aged 4 to 11 years inclusive, and
192 young children aged 1 to 3 years inclusive). Enrollment will be staggered, starting with 
the eldest age group. The decision to proceed to the next age group will be based on an
evaluation by the IDMC.
HIV-positive subjects can be enrolled as long as their general condition is good, ie, they are on 
antiretroviral treatment or have no signs or symptoms of immune incompetence, diagnosed on 
the basis of physical examination, medical history, and the investigator’s clinical judgment.
Community engagement will be sought in all stages.
Subsequently, subjects will be asked to provide individual consent to receive the vaccine 
regimen and for collecting safety data under the provisions of this protocol. The in- and 
exclusion criteria are described in the following 2 subsections. 
If there is a question about the inclusion or exclusion criteria below, the investigator or designee 
must consult with the appropriate sponsor representative and resolve any issues before enrolling 
a subject in the study. Waivers are not allowed. 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Status: Approved, Date: 2 October 2018
For a discussion of the statistical considerations of subject selection, refer to Section 11.3.
4.1.
Inclusion Criteria
Each potential subject must satisfy all of the following criteria to be enrolled in the study. 
Stage 1
1.
Documented community engagement by a community leader must be available. At the 
individual level, each subject must sign an ICF indicating that he or she understands the 
purpose of and procedures required for the study and is willing to participate in the study. In 
case the subject cannot read or write, the procedures must be explained and informed 
consent must be witnessed by a literate third party not involved in the conduct of the study.
2.
Must be a male or female subject aged 18 years or older at screening.
3.
Must be resident in the selected study community, with no intention to move from the study 
area within the next 5 months.
4.
Must be healthy on the basis of physical examination and clinical laboratory tests performed 
at screening. 
Subjects must meet the following laboratory criteria within 28 days before Day 1: 

Hemoglobin: women: ≥12.5 g/dL; men ≥13.0 g/dL

Hematocrit: ≥36%

Red blood cell (RBC) count: ≥4,500,000/mm3

White blood cell (WBC) count: ≥4,000/mm3

Platelets: ≥150,000/mm3

Alanine aminotransferase (ALT): ≤69 U/L

Aspartate aminotransferase (AST): ≤46 U/L

Creatinine: <109 µmol/L
Note: If laboratory screening tests are out of range, repeat of screening tests is 
permitted once using an unscheduled visit during the screening period to assess 
eligibility. 
5.
Female subjects of childbearing potential must use adequate birth control measures 
consistent with local regulations regarding the use of birth control for subjects participating 
in clinical studies from at least 14 days before the prime vaccination, with a negative urine 
β-hCG pregnancy test at screening and immediately prior to the prime vaccination, which 
shall occur no earlier than 14 days after the screening visit.
6.
Male subjects who are sexually active with a woman of childbearing potential must be 
willing to use condoms for sexual intercourse beginning prior to enrollment.
7.
Must pass the test of understanding (TOU). 
Note: The TOU will be administered after reading but before signing the ICF. If a subject 
fails the TOU on the first attempt, the subject must be retrained on the purpose of the 
clinical study and must take the test again. A subject who fails the TOU cannot participate 
in the study.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Status: Approved, Date: 2 October 2018
Subjects who fail screening in Stage 1 are allowed to be assessed again for eligibility to receive 
study vaccine in Stage 2.
Stage 2 
8.
Criterion modified per Amendment 5
1.1 Documented community engagement by a community leader must be available. At the 
individual level, adult subjects (aged 18 years and older at screening) must sign an ICF
indicating that he or she understands the purpose of the study and the procedures 
required for the study and is willing to participate in the study. In case the subject 
cannot read or write, the procedures must be explained and informed consent must be 
witnessed by a literate third party not involved in the conduct of the study. In case the 
subject’s age is below the legal cut-off age for consent (according to local regulations), 
the parent/legal guardian will be asked to give consent, and the subject will be informed 
about the study. Subjects aged 7 years and older will be asked to give positive assent. 
The assent procedure must be witnessed by an adult literate parent/legal guardian/third 
party not involved in the conduct of the study, and documented.
9.
Must be a male or female subject aged 1 year or older at screening. 
Note: Children of parents enrolled in this stage are eligible. 
10. Must be resident in the selected study community, with no intention to move from the study 
area during the subject's participation in the study.
11. Criterion modified per Amendment 5
4.1 Must be healthy on the basis of physical examination and clinical laboratory tests 
performed at screening. If the results of the laboratory screening tests are outside the 
institutional normal reference ranges, the subject may be included only if the 
investigator judges the abnormalities or deviations from normal to be not clinically 
significant or to be appropriate and reasonable for the population under study. This 
determination must be recorded in the subject's source documents and initialed by the 
investigator.
Note: The safety laboratory assessments at screening are to be performed within 
28 days prior to the prime 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, 
repeat of screening tests is permitted once using an unscheduled visit during the 
screening period to assess eligibility. 
12. Criterion modified per Amendment 4.
5.1 Sexually active female subjects of childbearing potential must use adequate birth control 
measures consistent with the local standards regarding the use of birth control for 
subjects participating in clinical studies and what is available from at least 14 days 
before the prime vaccination, with a negative urine β-hCG pregnancy test at screening 
and immediately prior to the prime vaccination, which shall occur no earlier than 
14 days after the screening visit.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Status: Approved, Date: 2 October 2018
13. Male subjects who are sexually active with a woman of childbearing potential must be 
willing to use condoms for sexual intercourse beginning prior to enrollment.
14. Subjects or the parent/legal guardian (for children) must pass the TOU. 
Note: The TOU will be administered after reading but before signing the ICF. If a subject or 
the parent/legal guardian (for children) fails the TOU on the first attempt, the subject or 
parent/legal guardian must be retrained on the purpose of the clinical study and must take 
the test again (2 re-takes are allowed). A subject who fails the TOU cannot participate in the 
study.
4.2.
Exclusion Criteria
Any potential subject who meets any of the following criteria will be excluded from participating 
in the study. 
Stage 1
1.
Women who are breast-feeding or known to be pregnant. A pregnancy test will be 
performed at screening in women of childbearing potential.
2.
Subjects who have an illness prior to vaccination. This does not include acute illnesses such 
as diarrhea or mild upper respiratory tract infection unless accompanied by body 
temperature >37.5°C.
3.
Subjects with any clinically significant acute or chronic medical condition that in the 
opinion of the investigator would preclude participation (eg, history of seizure disorders, 
bleeding/clotting disorder, cardiac disease, autoimmune disease, active malignancy, poorly 
controlled asthma, active tuberculosis, or other systemic infections). Subjects who identify 
themselves as being HIV-positive can be included as long as their general condition is good, 
ie, they are on antiretroviral treatment or have no signs or symptoms of immune 
incompetence.
4.
Subjects with anemia (defined as hemoglobin <10 g/dL).
5.
Subjects who have had a previous adverse reaction to vaccination excluding mild 
non-systemic adverse reactions.
6.
Subjects who are being treated with an immunosuppressive drug at the time of screening.
7.
Subjects who have received a blood transfusion or other blood products within 8 weeks of 
vaccination.
8.
Subjects who have been vaccinated with a candidate Ebola vaccine or have participated in 
another Ebola preventative or therapeutic biomedical intervention study (participation in 
observational or behavioral studies is allowed).
9.
Subjects who have been vaccinated with live-attenuated vaccines within 30 days before the 
prime vaccination, and with inactivated vaccines within 15 days before the prime 
vaccination.
10. Subjects who are known to have received any Ad26- or MVA-based candidate vaccine in 
the past.
11. Subjects who have been diagnosed with EVD or are under quarantine/have been exposed to 
Ebola.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Status: Approved, Date: 2 October 2018
12. Subjects who, in the opinion of the investigator, are unlikely to adhere to the requirements of 
the study or are unlikely to complete the full course of vaccination and observation.
13. Fever (body temperature ≥38.0°C). Temperature will be taken according to standardized 
temperature monitoring as per Ebola response regulations. Subjects with a fever of ≥38.0°C 
will be referred to the EVD assessment services.
Subjects who fail screening in Stage 1 are allowed to be assessed again for eligibility to receive 
study vaccine in Stage 2.
Stage 2
1.
Women who are breast-feeding or known to be pregnant. A pregnancy test will be 
performed at screening in women of childbearing potential.
2.
Subjects who have an illness prior to vaccination. This does not include acute illnesses such 
as diarrhea or mild upper respiratory tract infection unless accompanied by body 
temperature ≥38.0°C. 
3.
Subjects with any clinically significant acute or chronic medical condition that in the 
opinion of the investigator would preclude participation (eg, history of seizure disorders, 
bleeding/clotting disorder, cardiac disease, autoimmune disease, active malignancy, poorly 
controlled asthma, active tuberculosis, or other systemic infections). Subjects who identify 
themselves (or are identified by a parent/legal guardian in case of children) as being HIV-
positive can be included as long as their general condition is good, ie, they are on 
antiretroviral treatment or have no signs or symptoms of immune incompetence, diagnosed 
on the basis of physical examination, medical history, and the investigator’s clinical 
judgment.
4.
Subjects with anemia (defined as hemoglobin <8 g/dL for children aged ≥1 to <5 years, 
<9 g/dL for children aged ≥5 to <15 years, and <10 g/dL for subjects aged ≥15 years).
5.
Subjects who have had a previous adverse reaction to vaccination excluding mild non-
systemic adverse reactions.a
6.
Subjects who are being treated with an immunosuppressive drug at the time of screening.
7.
Subjects who have received a blood transfusion or other blood products within 8 weeks of 
vaccination.
8.
Subjects who have been vaccinated with a candidate Ebola vaccine or have participated in 
another Ebola preventative or therapeutic biomedical intervention study (participation in 
observational or behavioral studies is allowed).
9.
Subjects who have been vaccinated with live-attenuated vaccines within 30 days before the 
prime vaccination, and with inactivated vaccines within 15 days before the prime 
vaccination.
                                                
a 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 egg, egg products and aminoglycosides.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Status: Approved, Date: 2 October 2018
10. Subjects who are known to have received any Ad26- or MVA-based candidate vaccine in 
the past.
11. Subjects who have been diagnosed with EVD or are under quarantine/have been exposed to 
Ebola.
12. Subjects who, in the opinion of the investigator, are unlikely to adhere to the requirements of 
the study or are unlikely to complete the full course of vaccination and observation. 
13. Criterion modified per Amendment 5
13.1 Children with weight-per-height below 10th percentile according to the WHO (1- and 2-
year-olds) and Centers for Disease Control and Prevention (CDC) growth charts (3- to 
11-year-olds).2,13
14. Fever (body temperature ≥38.0°C). Temperature will be taken according to standardized 
temperature monitoring as per Ebola local response regulations. Subjects with a fever of 
≥38.0°C will be referred to routine medical follow-up (including the EVD assessment 
services, if applicable).
15. Subjects who have received a meningitis vaccine in the past.
NOTE: Investigators should ensure that all study enrollment criteria have been met prior to the 
prime vaccination on Day 1. If a subject’s clinical status changes (including receipt of additional 
medical records or available laboratory results in Stages 1 and 2) after screening but before the 
prime vaccination is given such that he or she no longer meets all eligibility criteria, then the 
subject will be excluded from participation in the study. Section 17.4 describes the required 
documentation to support meeting the enrollment criteria.
4.3.
Prohibitions and Restrictions
Potential subjects must be willing and able to adhere to the following prohibitions and 
restrictions during the course of the study to be eligible for participation:
1.
Criterion modified per Amendment 5
1.1 Subjects enrolled in Stage 1 should be willing to reside in the study area for 5 months 
after the prime vaccination. Subjects in Stage 1 who consent to the third vaccination must 
be willing to reside in the study area for at least 6 months post-third vaccination. Subjects 
enrolled in Stage 2 should be willing to reside in the study area throughout the subject's 
participation to the study. Appropriate measures will be installed to uniquely identify 
subjects in order to ensure correct application of the prime-boost regimen.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL3001 Amendment 7
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Status: Approved, Date: 2 October 2018
2
Criterion modified per Amendment 5
2.1 For sexually active female subjects of childbearing potential, it should be confirmed that 
adequate birth control measures consistent with what is available and the local standards
regarding the use of birth control for subjects participating in clinical studies were used 
from at least 14 days before the prime vaccination with a negative urine β-hCG pregnancy 
test at screening and a negative urine β-hCG pregnancy test immediately prior to each study 
vaccination. All male and female subjects, except for female subjects of non-childbearing 
potential, will be asked to use adequate birth control for sexual intercourse until at least 
3 months after the prime vaccination or up to 28 days after the boost vaccination (whichever 
takes longer). Subjects receiving the third vaccination in Stage 1 will be asked to use 
adequate birth control for sexual intercourse from at least 14 days prior and until 3 months 
after the third vaccination.
3.
Analgesic/antipyretic medications and nonsteroidal anti-inflammatory drugs (NSAIDs) may 
be used post-vaccination only in case of medical need (eg, body temperature ≥38.0°C or 
pain) and for subjects in Stage 1 and Stage 2, their use must be documented. If the 
temperature does not abate or is not controlled after 24 hours, the person will be instructed 
to contact the study personnel and/or consult the nearest health care unit to her/his 
household/section. Use of these medications as routine prophylaxis prior to study vaccine 
administration is discouraged. For details, refer to Section 9.1.6.
4.
Criterion modified per Amendment 5
4.1 Criterion modified per Amendment 6
4.2 Subjects should not receive live-attenuated vaccines from 30 days before the prime 
vaccination until 30 days after the boost vaccination and from 30 days before until 30 
days after the third vaccination in Stage 1, and inactivated vaccines from 15 days before 
or after administration of prime and boost vaccination and 15 days before or after third 
vaccination in Stage 1. The possibility exists that a vaccine preventable disease such as 
measles can start circulating and causing outbreaks or an epidemic during the course of 
the study. If this happens, receipt of live-attenuated vaccines such as measles vaccine 
will be allowed but will be documented.
5.
Vaccination posts and clinics will implement standard Ebola prevention methods such as 
provision of handwashing stations and temperature checks and all vaccinees and staff will 
follow these recommendations during scheduled and unscheduled visits.
5.
TREATMENT ALLOCATION AND BLINDING
Community Engagement
This study will build on the community engagement and community capacity established in 
collaboration/coordination with non-governmental organizations (NGOs) and institutions 
performing social mobilization and contact tracing for Ebola control.
Direct community engagement for this study will begin as early as possible and MoHS, 
UNICEF, UNMEER, WHO and other government authorities will be consulted for their input. 
Guidance will also be sought from groups currently conducting social mobilization for the Ebola 
response.

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A key aspect of the initial, community fact-finding, research work during the period prior to the 
study active phase of implementation (vaccination) will be a stakeholder analysis, results of 
which will be used to identify relevant stakeholders to be considered in community engagement 
such as paramount chiefs, sub-chiefs, mesquites (imams), churches, schools, law enforcement, 
government structures at community level, health-related committees, and development-related 
committees. One of the main tasks of the study staff will be to keep dialogue open and ongoing 
between the study researchers, the MoHS and the community at large.
Community engagement will be an ongoing process through regular contacts with community 
groups and designated study team members. A combination of mechanisms will be utilized, such 
as community meetings, workshops with key stakeholders, participant meetings, and others. 
Community advisory boards, comprising key influential figures with the community, together 
with members of the local population, will be established and continually engaged to provide a 
dialogue between the community and study team and allow the community to provide feedback 
on any concerns that they may have. Community engagement will also allow researchers to 
receive feedback from the community on social harms, individual and community level risks, 
perceptions about the study, and vaccination implementation challenges. All study staff and 
stakeholders will receive training in Good Clinical Practice (GCP)/research ethics before 
commencement of the intervention (Ebola vaccination). The paramount chief for the relevant 
study area will be asked to sign an agreement form to agree the study to take place within his 
community.
Community engagement will also be a component of other study processes such as the 
communication plan, especially the dissemination of study results to the community. Overall,
strong community engagement will allow the establishment of a partnership between 
communities, participants and researchers to ensure the latter discharge their responsibilities 
ethically in the study communities. 
The selected study area has a population of several thousand people. To be able to handle 
demand and expectations, the following process will take place as a part of community 
engagement:

Numbering of all the households in the community (this has already been done by the 
national authorities).

Conducting an open lottery, presided over by community leaders, at which these numbered 
households are drawn by lot and listed in sequential order on a formal document which will 
be signed off by the community leaders.

Households will then be visited in order and asked if they would like to join the study; if the 
household declines, the next one on the list will be approached and asked to join, the process 
being continued until a sufficient number have been invited for the study.
Community members who became aware of the study through other community engagement 
activities but were not part of the invitation process, and decide to volunteer for participation at 
the clinic, will not be rejected. However, priority will be given to those responding to the 
invitation process.

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Sampling/Recruitment of Population 
Appropriate measures will be installed to uniquely identify subjects in order to ensure correct 
application of the prime-boost regimen.
Randomization 
There will be no randomization in Stage 1. Assignment of the third vaccination in Stage 1 will be 
done using Interactive Voice/Web Response System (IVRS/IWRS)
The randomization through IVRS/IWRS in Stage 2 will be 3:1 (Ad26.ZEBOV/MVA-BN-
Filo:active control) and will be stratified by age group. 
Blinding
Blinding procedures are not applicable for Stage 1.
Within each age group of Stage 2, study-site personnel (except for those with primary 
responsibility for study vaccine preparation and dispensing), sponsor personnel (except for 
specifically designated sponsor personnel who are independent of the study) and subjects will be 
blinded to the study vaccine allocation until all subjects have completed at least the 6 month 
post-boost visit or discontinued earlier and the database has been locked for that age group. 
The investigator will not be provided with randomization codes. The codes will be maintained 
within the IVRS/IWRS, which has the functionality to allow the investigator to break the blind 
for an individual subject.
Data that may potentially unblind the study vaccine allocation
(ie, study vaccine 
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 will include making special provisions, such as segregating the data in question from view 
by the investigators, clinical team, or others as appropriate, until the time of database lock and 
unblinding. The pharmacy and preparation of study vaccines will be monitored by an 
independent study vaccine monitor (see Section 17.8).
Under normal circumstances, the blind of each age group in Stage 2 should not be broken until 
the last subject in the age group has completed at least the 6 month post-boost visit or 
discontinued earlier and the database for the respective age group has been locked. Otherwise, 
the blind should be broken only if a specific emergency treatment/course of action would be 
dictated by knowing the treatment status of the subject. In such cases, the investigator may, in an 
emergency, determine the identity of the treatment by contacting the IVRS/IWRS. It is 
recommended that the investigator contact the sponsor or its designee if possible to discuss the 
particular situation, before breaking the blind. Telephone contact with the sponsor or its designee 
will be available 24 hours per day, 7 days per week. In the event the blind is broken, the sponsor 
must be informed as soon as possible. The date and reason for the unblinding must be 
documented by the IVRS/IWRS, in the appropriate section of the Case Report Form (CRF), and 

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in the source document. The documentation received from the IVRS/IWRS indicating the code 
break must be retained with the subject's source documents in a secure manner. 
When the last subject in a given age group has completed at least the 6-month post-boost visit or 
discontinued earlier and the database for that age group has been locked, randomization codes 
may be disclosed for that age group. Should an interim analysis be performed prior to the 6 
months post-boost visit of the last subject in a given age group, only those involved in the 
analysis and decision making will be unblinded.
If the randomization code is broken by the investigator or the study-site personnel, the subject 
must discontinue further study vaccine 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 subject should not discontinue further study vaccine administration and may 
remain in the study (if the randomization code is still blinded to the study-site personnel and the 
subject).
6.
DOSAGE AND ADMINISTRATION
All subjects in Stage 1 and all subjects randomized to the Ad26.ZEBOV/MVA-BN-Filo arms in 
Stage 2 will receive the following as a 0.5 mL IM injection into either deltoid in the upper arm
(or, if needed, in the thigh):

Ad26.ZEBOV: 5x1010 vp on Day 1

MVA-BN-Filo: 1x108 Inf U on Day 57
Subjects in Stage 1 who consent to this will receive a third vaccination using Ad26.ZEBOV at 
5x1010 vp at least 2 years post-prime vaccination.
Subjects in the control arm of Stage 2 will receive the WHO-prequalified MenACWY vaccine as 
prime on Day 1 and placebo as boost on Day 57. The MenACWY vaccine will be administered 
as an IM injection into either deltoid in the upper arm. For details, refer to Section 14.1.3.
Children aged less than 2 years at randomization will receive a third vaccination at 3 months post 
boost with either placebo (Ad26.ZEBOV/MVA-BN-Filo arm) or MenACWY (control arm).
The vaccination schedule is presented in Table 2.

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Table 2: 
Study Vaccination Schedules 
N 
(per group)
Prime 
(D1)
Boost
(D57)
Third vaccination 
(2 years post prime [Stage 1]
3 months post boost [Stage 2]) a)
Stage 1
Adults (≥18 years)
40
Ad26.ZEBOV 5x1010 vp
MVA-BN-Filo 1x108 Inf U
Ad26.ZEBOV 5x1010 vp
Stage 2
Adults (≥18 years)
300
Ad26.ZEBOV 5x1010 vp
MVA-BN-Filo 1x108 Inf U
NA
100
MenACWY
placebo
NA
Adolescents (12-17 years inclusive)
144
Ad26.ZEBOV 5x1010 vp
MVA-BN-Filo 1x108 Inf U
NA
48
MenACWY
placebo
NA
Children (4-11 years inclusive)
144
Ad26.ZEBOV 5x1010 vp
MVA-BN-Filo 1x108 Inf U
NA
48
MenACWY
placebo
NA
Young children (1-3 years inclusive)
144
Ad26.ZEBOV 5x1010 vp
MVA-BN-Filo 1x108 Inf U
Placebo (<2 years)
48
MenACWY
placebo
MenACWY (<2 years)
D: day; Inf U: infectious units; N: number of subjects per group to receive study vaccine; NA: not applicable; vp: viral particles.
a) The third vaccination in Stage 2 is only applicable for children aged less than 2 years at randomization.
Study vaccines in Stage 2 will be prepared by an unblinded pharmacist or qualified staff member 
with primary responsibility for study vaccine preparation and dispensing and who is not involved 
in any other study-related procedures. Subjects will be administered the study vaccines in a 
masked syringe in a way that maintains double-blinding.
Upon completion of the study, sites may offer MenACWY to the Ad26.ZEBOV/MVA-BN-Filo 
arm and the Ad26.ZEBOV/MVA-BN-Filo vaccine (if licensed and/or WHO-prequalified) to the 
control arm upon consultation with the health authorities.
When choosing an arm for the injection, it should be considered whether there is an arm injury, 
local skin problem, and/or significant tattoo that preclude administering the injection or will 
interfere with evaluating the arm after injection. 
For subjects in Stage 1 and Stage 2, it is recommended that the boost vaccination will be 
administered in the opposite deltoid to that used for the prime vaccination. For subjects in 
Stage 1, the third vaccination can be administered in either deltoid. Study vaccines in Stage 2
will be administered in a way that maintains double-blinding. It should be recorded in the CRF in 
which arm the vaccination has been administered.
If needed, the vaccination might also be administered in the thigh (especially for infants).
No local or topical anesthetic will be used prior to the injection.
The Site Investigational Product Procedures Manual specifies the maximum time that will be 
allowed between preparation and administration of the study vaccine. 
The date and time of each study vaccine administration will be recorded.

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7.
TREATMENT COMPLIANCE
All study vaccine will be administered at study clinics or satellite vaccination posts. The date and 
time of each study vaccine administration will be recorded.
In order to support vaccination compliance, a separate Innovative Medicines Initiative (IMI)
Ebola+ initiative, EBODAC, with focus on “Deployment and Compliance” was established. The 
overall objective of EBODAC is to develop a communication and engagement strategy including 
the development of appropriate technology and tools in order to maximize Ebola vaccination 
impact. 
EBODAC will provide:
1.
A communication strategy and tools, including a mobile technology platform, to increase 
acceptance and compliance with Ebola vaccination and building confidence with the broader 
population.
2.
Tools, services, and mobile technologies to allow an effective recall of the vaccinee for the 
boost vaccination.
3.
An identification tool of vaccinees to ensure correct application of the prime-boost regimen.
8.
PRESTUDY AND CONCOMITANT THERAPY
A subject should not receive a live-attenuated vaccine from 30 days before the prime vaccination 
until 30 days after the boost vaccination unless a vaccine preventable disease such as measles 
emerges. Immunizations with inactivated vaccines should be administered at least 15 days before 
or after administration of any study vaccine in order to avoid any potential interference in 
efficacy of the routine immunizations or the interpretation of immune responses to study 
vaccines, as well as to avoid potential confusion with regard to attribution of adverse reactions. 
Otherwise, a subject 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 young children in Stage 2, parents 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 does not have a card or cannot show it, the parent will 
be asked whether the child has received a measles vaccination within the last 30 days.
Chronic or recurrent use of medications that modify the host immune response (eg, cancer 
chemotherapeutic agents, systemic corticosteroids) are discouraged.
Analgesic/antipyretic medications (paracetamol) and NSAIDs may be used post-vaccination only 
in case of medical need (eg, body temperature ≥38.0°C or pain). The use of these medications in 
Stage 1 and Stage 2 must be documented. Use of these medications as routine prophylaxis prior 
to study vaccine administration is discouraged.
Subjects who develop anemia during the study (defined as hemoglobin <8 g/dL for children aged 
≥1 to <5 years, <9 g/dL for children aged ≥5 to <15 years, and <10 g/dL for subjects aged 

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≥15 years) will be provided with appropriate supplements (iron, Vitamin C) and followed-up 
accordingly.
Prestudy therapies administered up to 30 days prior to the start of screening must be recorded at 
screening. Concomitant therapies must be recorded from the screening onwards until 28 days
after the prime vaccination and then again until 28 days post-boost vaccination (Stage 1 and 2) 
and until 28 days post-third vaccination (Stage 1). At the other time points, concomitant 
therapies are only to be recorded if given in conjunction with serious adverse events and IREs.
9.
STUDY EVALUATIONS
9.1.
Study Procedures
9.1.1.
Overview
The Time and Events Schedules summarizes the frequency and timing of immunogenicity and 
safety measurements applicable to this study. Additional study visits may be required if in the 
investigator’s opinion, further clinical or laboratory evaluation is needed.
Additional urine pregnancy tests may be performed, as determined necessary by the investigator 
or required by local regulation, to establish the absence of pregnancy at any time during the 
subject’s participation in the study.
Approximately 124.2 or 164.4 mL (Stage 1, without or with third vaccination, respectively) or
87.3 or 98.5 mL (Stage 2, long-term follow-up period until 1 year or 2 years post-prime, 
respectively) of blood will be drawn from adults (≥18 years of age) and approximately 65.6 mL 
of blood will be drawn from adolescents (≥13 and <18 years of age) during the study. This 
volume remains well below the limits of standard blood donation.
For children (<13 years), 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.5 The allowable blood volume calculations are 
based on the 10th percentile for growth charts for 1- to 2-year-old children13 and 3- to 11-year-old 
children.2
For details on the approximate blood sampling volumes collected by visit and the cumulative 
blood volumes, refer to the Time and Events Schedules.
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples which could increase the total blood volume indicated above. In case a subject has fever, 
but does not meet the EVD definition, an unscheduled blood sample may be taken to perform a 
PCR test to exclude EVD.
Visit windows are provided in the Time and Events Schedules for the different stages in the 
study. If a subject did not receive a study vaccine on the planned day of vaccination, the timings 

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of the next visits post-vaccination (see Time and Events Schedules) will be determined relative 
to the actual day of vaccination.
9.1.2.
Screening Phase
Up to 28 days before the baseline visit (Day 1; day of prime vaccination), screening assessments 
as indicated in the Time and Events Schedules will occur. Screening may be split into multiple 
days or visits. Subjects whose screening period was longer than the protocol-defined 28 days as a 
result of a study pause or factors outside the control of the study will be allowed to rescreen 
once.
For male subjects and female subjects of non-childbearing potential, there will be no minimum 
duration of the screening period and it will last only for the time required to verify eligibility 
criteria. 
For female subjects of childbearing potential, it should be confirmed that adequate birth control 
measures consistent with what is available and the local standards regarding the use of birth 
control for subjects participating in clinical studies were used from at least 14 days before the 
prime vaccination with a negative urine β-hCG pregnancy test at screening, a negative urine 
β-hCG pregnancy test immediately prior to the prime vaccination (which shall occur no earlier 
than 14 days after the screening visit) and a negative urine β-hCG pregnancy test immediately 
prior to the boost vaccination and third vaccination (Stage 1). 
All male and female subjects, except for female subjects of non-childbearing potential, will be 
asked to use adequate birth control for sexual intercourse until at least 3 months after the prime 
vaccination or up to 28 days after the boost vaccination (whichever takes longer). See 
Section 4.3 for the requirements of the third vaccination in Stage 1.
Only subjects complying with the criteria specified in Section 4 will be included in the study. 
The investigator will provide detailed information on the study to the subject and will obtain 
informed consent/assent (see Section 16.2.3 for details). 
After reading but before signing the ICF, subjects (for children, this would be the parent or 
guardian) must pass the TOU. Subjects in Stage 2 who fail may repeat the test twice. If both the 
parent or guardian and the child will be enrolled in the study, the parent/guardian will need to 
complete the TOU twice (ie, one for the parent/guardian and one for the child). In case the 
parent/guardian consents for multiple children of the same family, the TOU needs to be 
completed only once, ie, for the first child of the family enrolled in the study. In case the TOU 
information would change while recruiting multiple children of the same family, the TOU should 
be completed again for the first child of the family that was enrolled after the TOU change had 
occurred. The TOU is a questionnaire to document the subject’s understanding of the study (for 
details, see Section 16.1 and Attachment 2).

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The following is performed to determine the eligibility requirements:
Review of all inclusion and exclusion criteria
Review of prohibitions and restrictions
Review of medical history and demographics
Review of prestudy therapies
Urine pregnancy test (for sexually active women of childbearing potential)
Blood sampling for hematology and chemistry (fasting or non-fasting)
Full physical examination (including body length/height and weight)
Measurement of vital signs (heart rate and blood pressure [supine], body temperature)
The overall eligibility of the subject 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) that lead to exclusion is allowed once using an unscheduled visit during the screening 
period to assess eligibility. Study subjects who qualify for inclusion will be contacted and 
scheduled for enrollment and prime vaccination within 28 days.
All adverse events will be collected from signing of the ICF onwards until 56 days after the 
boost vaccination in Stage 1 and then again from the day of the third vaccination until 28 days 
after the third vaccination, and from signing of the ICF onwards until 28 days after the prime 
vaccination in Stage 2, and then again until 28 days after the boost vaccination. Serious adverse 
events and IREs will be collected from signing of the ICF onwards until subjects have completed 
the study.
9.1.3.
Vaccination Period
The investigator should ensure that all enrollment criteria have been met during screening. If a 
subject’s clinical status (including available laboratory results or the receipt of additional medical 
records) after screening but before the prime vaccination on Day 1 changes such that the subject 
no longer meets all enrollment criteria, then the subject will be excluded from participation in the 
study.
Following a re-check of the inclusion and exclusion criteria (only for the prime vaccination), 
check of the contraindications (only for the boost [Stage 1 and Stage 2] and third vaccination
[Stage 1]), a urine pregnancy test (for sexually active women of childbearing potential), a brief 
physical examination (including body length/height and weight in children aged 12 months up to 
and including 24 months), measurements of vital signs, and collection of a blood sample for
hematology and chemistry (for details, see Section 9.3.2), subjects will receive the study vaccine 
on Day 1, Day 57 and at least 2 years post prime (Stage 1 only) as described in Section 6. 
Subjects will have a blood draw prior to each vaccination for immunologic assays. 
After the prime, boost and third (Stage 1 only) vaccinations, subjects will be asked to remain at 
the clinic or vaccination post and will be closely observed by the study staff for 60 minutes 

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(Stage 1 prime and boost vaccination) or 30 minutes (Stage 1 third vaccination and Stage 2 prime 
and boost vaccination) after vaccination, and symptoms of unsolicited and solicited local and 
systemic adverse events will be evaluated during this period, and documented at the end of the 
observation period. Vital signs including body temperature will also be obtained at the end of the 
observation period. The observation time may be extended if deemed necessary by the study 
staff.
Upon discharge from the clinic or vaccination post after the prime and boost vaccination and 
after the third vaccination (Stage 1 only), subjects will also receive a diary, a thermometer, and a 
ruler to measure local solicited reactions and body temperature and will be trained on how to 
collect this information. Subjects will record symptoms of solicited local and systemic adverse 
events in the diary in the evening after each vaccination and then daily for the next 7 days. 
Diaries will be completed at home by either a project field worker who will contact the subject at 
home or by the subject (for children: the parent/legal guardian) and checked by a project field 
worker.
Subjects will visit the clinic or vaccination post for assessments 7 days post prime and 7 days 
post boost as described in the Time and Events Schedules. The investigator or clinical designee 
will review information from the subject’s diary and examine the injection site for occurrences of 
redness of skin, swelling/induration, pain/tenderness, and/or itching in order to complete the 
relevant parts of the CRF. The diary should be completed by the end of the Day 8 and Day 64
visit (Stage 1) and the Day 8 and Day 8 post-boost visit (Stage 2). A brief physical examination 
(including body length/height and weight in children aged 12 months up to and including 
24 months at the time of the prime and the boost vaccination) and measurements of vital signs 
including body temperature will be performed, and a blood sample for hematology and chemistry 
will be collected.
Subjects in Stage 2 should also visit the clinic on Day 29 for safety assessments (adults and 
children) and sampling for immunogenicity assessments (adults only).
Subjects in Stage 1 receiving the third vaccination will visit the clinic or vaccination post 4 days 
post-third vaccination for sampling for immunogenicity assessments. A next visit is scheduled 
7 days post-third vaccination. At this time point, they will follow the same assessments and 
procedures as described above for the 7-day post-prime and 7-day post-boost vaccination visits, 
except for measurements of vital signs (will not be performed). The diary should be completed 
by the end of the Day 8 post-third vaccination visit.
Adverse events and serious adverse events will be collected and documented on the CRFs, 
together with the information on any concomitant medications. For reporting of immediate 
reportable events (IREs), refer to Section 12.3.3.

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9.1.4.
Post-Boost and Post-Third Vaccination Period
Stage 1
Subjects will come to the clinic or vaccination post on Day 78 and Day 156 after the prime 
vaccination for safety evaluations. A brief physical examination and measurements of vital signs 
including body temperature will be performed, and a blood sample for hematology and chemistry 
will be collected (Day 78 visit only).
Subjects will have a blood draw for immunologic assays on Day 78 and Day 156 after the prime 
vaccination.
Subjects in Stage 1 receiving the third vaccination will come to the clinic or vaccination post on 
the Day 22 post-third vaccination visit for safety evaluations. A brief physical examination will 
be performed. In addition, a blood draw for immunologic assays will be performed.
Stage 2
Subjects will come to the clinic or vaccination post on the Day 22 post-boost visit (adults and 
children) and the 3-month post-boost visit (only for young children aged less than 2 years at 
randomization) for safety evaluations. A brief physical examination and measurements of vital 
signs including body temperature will be performed.
Subjects will also have a blood draw for immunologic assays on Day 22 post boost.
Children aged less than 2 years at the time of randomization will receive a third vaccination at 
3 months post boost, with MenACWY (for children in the control arm) or placebo 
(Ad26.ZEBOV/MVA-BN-Filo arm). Subject diaries will not be distributed. Children that 
experience any symptoms will be invited to come for an unscheduled visit as needed. 
9.1.5.
Long-Term Follow-Up
In both Stage 1 and Stage 2, subjects will be contacted by telephone on a periodic basis between 
visits during long-term follow-up to assess safety. In addition, subjects may be contacted 
approximately 1 month after their last visit to inquire after their general health status. These calls 
will not be included in the clinical database.
Stage 1
Subjects will enter the long-term follow-up, and visit the clinic or vaccination post on Days 180,
240 and 360 post prime for collection of serious adverse event information and IREs. 
Blood will be drawn for immunologic assays at the Day 360 post-prime visit.
Thereafter, subjects in Stage 1 who do not consent to receive the third vaccination will visit the 
clinic or vaccination post every 6 months until 36 months post prime for collection of serious 
adverse event information and IREs and immunogenicity assessments.

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Subjects who consent to receive the third vaccination, will visit the clinic at the Day 540 post-
prime visit and will enter the third vaccination schedule 6 months later (at least 2 years post
prime). During the long-term follow-up period of the third vaccination schedule, subjects will 
visit the clinic or vaccination post at the 6-month post-third vaccination visit and on the Day 360
post-third vaccination visit. At these visits, serious adverse event information and IREs will be 
collected and blood will be drawn for immunologic assays. A brief physical examination will 
only be performed when related to serious adverse events and IREs.
Stage 2
Subjects will enter the long-term follow-up, and visit the clinic or vaccination post on the 
6-month post-boost visit and the Day 360 post-prime visit. Subjects in Stage 2 will be 
approached for enrollment into the VAC52150EBL3005 study for further follow-up of safety 
and immunogenicity for up to a total of 60 months after the prime vaccination. Adult subjects 
who consent to extend the long-term follow-up period for up to 2 years post prime, will also visit 
the clinic or vaccination post on the Day 540 post-prime visit and the 2-year post-prime visit. At 
all visits, serious adverse event information and IREs will be collected. Vital signs will be 
measured on the 6-month post-boost visit only. Brief physical examinations at the long-term 
follow-up visits will only be performed when related to serious adverse events and IREs.
Blood will be drawn for immunologic assays at the 6-month post-boost visit and the Day 360 
post-prime visit (all subjects) and at the 2-year post-prime visit (adults only, if applicable).
9.1.6.
Evaluation of Fever
Subjects may exhibit general signs and symptoms associated with the administration of the study 
vaccines, including fever and chills (see Section 1.2.4). Subjects will be counseled to 
immediately call or contact the study personnel if they are feeling ill following vaccination and 
study personnel will investigate any fever ≥38.0°C following the fever management algorithm 
(see Attachment 3) and national guidelines.
If the subject experiencing fever ≥38.0°C does not meet the modified case definition for EVD 
(available in Attachment 3), study personnel will refer the subject to the hospital if the subject 
needs medical care and, if the subject has mild symptoms and does not need immediate medical 
care, or the fever is <38.0°C and study personnel considers that it merits attention, investigate 
any cause of fever (malaria, respiratory infections, etc.) and treat it appropriately. The fever will 
be classified as “vaccine-related” if other causes of fever are ruled out. An unscheduled blood 
sample may be taken to perform a PCR test to exclude EVD. 
If fever is not deemed to be a reaction to the vaccine and another cause needing medical care is 
detected, the subject will be referred for further investigation/confirmatory diagnosis and 
eventual treatment at the corresponding hospital. 
In case a subject has fever, and meets the modified EVD case definition, study personnel will 
call the Ebola alert line (if still in place) and coordinate with the corresponding authorities the 
transport and evacuation of the patient to the Ebola holding or treatment center for evaluation, 

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diagnosis and management. Note that Sierra Leone was declared Ebola-free on 7 November 
2015. A 90-day period of enhanced surveillance will end 5 February 2016. The evaluation of 
fever pertaining to Ebola disease will be carried out until instructions to alter management are
received from the relevant authorities in the country.
In order to reduce the incidence of fever induced by malaria, subjects in Stage 2 will receive 
insecticide treated bed nets (ITNs) at the time of their prime vaccination. Subjects currently 
enrolled in Stage 1 will receive these at their next convenient booked visit. To further minimize 
the event of a vaccine-associated fever being misclassified as an EVD suspect case, the study 
will keep close contact/collaboration with the national Ebola surveillance center to monitor any 
possible EVD that has been detected in the past 21 days or under investigation in the community 
so that the fever investigation can have up-to-date information to rule out an epidemiological 
link.
9.1.7.
Early Withdrawal
Subjects withdrawn from study vaccine administration must not receive any further study 
vaccine, but should continue to be monitored for safety. Subjects may be followed-up for 
immunogenicity but only if this does not result in an additional risk (see Section 10.2). 
In case of early withdrawal due to an adverse event, the investigator or clinical designee will 
collect all information relevant to the adverse event and safety of the subject, and will follow the 
subject until resolution of the adverse event or until reaching a clinically stable endpoint. If 
feasible, blood will be drawn for immunologic assays. 
Subjects who wish to withdraw consent will be offered an optional visit for safety follow-up 
(before the formal withdrawal of consent). The subject has the right to refuse. For more 
information, see Section 10.4.
9.2.
Immunogenicity
9.2.1.
Endpoints
The immunogenicity endpoint of the study includes the evaluation of antibody responses. 
Depending on assay and/or sample availability any of the following assays might be performed:

EBOV GP ELISA: to determine the binding antibody levels elicited by vaccination.

VNA: neutralizing antibody reactivity against the EBOV GP defined as the serum titer that 
is able to inhibit viral infection by a certain percentage (IC50, IC80 or IC90). 

ELISA, VNA, and/or PRNT: to explore the binding and/or neutralizing antibody responses
against the adenovirus and/or MVA vector.
9.2.2.
Evaluations
Venous blood samples will be collected from all subjects from Stage 1 and Stage 2 to assess 
humoral immune responses to the vaccines.

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The samples will be collected at the time points and in volumes as indicated in the Time and 
Events Schedules.
The immunologic assays and purposes are summarized in Table 3 below. Sample collection and 
processing will be performed by the site staff 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.
The analysis of the immunogenicity samples will be done at a central laboratory.
Table 3:
Summary of Potential Immunologic Assays (Serology)
Assay 
Purpose
ELISA
Analysis of antibodies binding to EBOV GP
Virus neutralization assay 
Analysis of neutralizing antibodies to EBOV GP
ELISA and/or neutralization assay
Analysis of binding and/or neutralizing antibodies against Ad26 
and/or MVA vectors 
EBOV: Ebola virus; ELISA: enzyme-linked immunosorbent assay; GP: glycoprotein
9.3.
Safety 
9.3.1.
Endpoints
The safety and tolerability endpoints are:

Solicited local and systemic adverse events (reactogenicity), collected until 7 days after the 
prime and boost vaccination (Stage 1 and Stage 2) and the third vaccination (Stage 1) as 
recorded by the subjects (or, when appropriate, by a project field worker, a caregiver, 
surrogate, or the subject's legally acceptable representative) in a diary during daily home 
contacts with a project field worker.

Solicited local and systemic adverse events (reactogenicity), collected until 60 minutes after 
the prime and boost vaccination and until 30 minutes after the third vaccination in all 
subjects from Stage 1, and until 30 minutes after each vaccine administration in all subjects 
from Stage 2.

Unsolicited adverse events, collected by the investigator or the clinical designee from 
provision of informed consent onwards until 56 days after the boost vaccination in Stage 1 
and then again from the day of the third vaccination until 28 days after the third vaccination, 
and from provision of informed consent onwards until 28 days after the prime vaccination in 
Stage 2 and then again until 28 days after the boost vaccination. (Note: events that started 
before the third vaccination but are still present at the time of third vaccination should also 
be recorded).

Serious adverse events, including deaths, and IREs collected in all subjects from Stage 1 and 
Stage 2 from provision of informed consent onwards until the subject’s last study visit.
9.3.2.
Evaluations
Details regarding the IDMC are provided in the IDMC Charter. See also Section 11.7.

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Serious adverse events, including deaths, and IREs will be collected from all subjects and during 
all stages of the study from signing of the ICF onwards until the subject’s last study visit.
Deaths in Stage 1 and Stage 2 will be followed-up and investigated actively to determine if the 
death is related to the vaccine. If, according to the WHO case definition and algorithm, the death 
is suspected to be due to EVD, the case will be referred to the corresponding local Ebola 
response authorities for investigation per WHO protocol/guidance.a
Any death will be immediately followed-up, recorded, reported per standard operating 
procedures, investigated and referred to the IDMC. If the death is deemed to be vaccine-related, 
the study will pause until IDMC has reviewed all pertinent data and allocates causality. If, 
according to the WHO case definition and algorithm, the death is suspected to be due to EVD, 
the case will be referred to the corresponding local authorities for investigation (verbal autopsy) 
per WHO protocol/guidance.
The study will further include the following evaluations of safety and tolerability according 
to the time points in the Time and Events Schedules:b
Adverse Events
All adverse events will be reported by the subject (or, when appropriate, by a caregiver, 
surrogate, or the subject's legally acceptable representative) from signing of the ICF onwards 
until 56 days post boost in Stage 1 and then again from the day of the third vaccination until 
28 days after the third vaccination, and from signing of the ICF onwards until 28 days after the 
prime vaccination in Stage 2 and then again until 28 days after the boost vaccination. 
Solicited local and systemic adverse events (reactogenicity; see below) will be reported by the 
subject (or, when appropriate, by a project field worker, a caregiver, surrogate, or the subject's 
legally acceptable representative) in the diary each day until 7 days after the prime and boost 
vaccination (Stage 1 and Stage 2) and the third vaccination (Stage 1). If a solicited local or 
systemic adverse event is not resolved at Day 8, Day 64 or Day 8 post-third vaccination (Stage 
1), or at Day 8 or Day 8 post boost (Stage 2), the follow-up information will be captured on the 
diary and the date of last symptoms and maximum severity will be recorded in the diary after 
resolution.
Any clinically relevant changes occurring during the study must be recorded on the Adverse 
Event section of the CRF.
                                                
a
Available 
at: 
http://www.who.int/csr/resources/publications/ebola/Corrected%20CoverEboladoc1.pdf?ua=1, 
accessed 12 August 2016.
b
Note that diaries are only applicable for the prime and boost vaccination in Stage 1 and Stage 2, and for the third 
vaccination in Stage 1. Solicited local and systemic adverse events (reactogenicity) will be reported until 
60 minutes after the prime and boost vaccination in all subjects from Stage 1 and until 30 minutes after the third 
vaccination in all subjects from Stage 1 and after the prime and boost vaccination in all subjects from Stage 2.

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Any clinically significant abnormalities persisting at the end of the study/early withdrawal will 
be followed by the investigator or clinical designee until resolution or until a clinically stable 
endpoint is reached.
Adverse events will be followed by the investigator or clinical designee as specified in 
Section 12.
Solicited Adverse Events
Solicited adverse events are precisely defined events that subjects are specifically asked about and 
which are noted in the diary. The investigator or clinical designee should discuss the information 
from the diary with the subject or the subject's legally acceptable representative, document the
relevant information in the clinic chart, and complete the relevant parts of the CRF as described 
in the CRF Completion Guidelines.
Solicited Local (Injection Site) Adverse Events
Instructions will be provided on how to note the following occurrences at the injection site daily 
until 7 days after the prime and boost vaccination (Stage 1 and Stage 2) and the third vaccination 
(Stage 1). 
redness of skin
swelling/induration
pain/tenderness 
itching at the injection site
These occurrences will be recorded in the diary.
Solicited Systemic Adverse Events
Instructions will be provided on how to record daily body temperature using a thermometer 
provided for home use. Body temperature should be recorded in the evening after the prime and 
boost vaccination (Stage 1 and Stage 2) and the third vaccination (Stage 1), and then daily for the 
next 7 days in the diary. Body temperature should be measured at approximately the same time 
each day. If more than one measurement is made on any given day, the highest value will be 
recorded in the CRF. Any fever will be investigated by the investigator or clinical designee for 
the possibility of Ebola. A body temperature equal to or higher than 38.0°C will be recorded by 
the investigator or clinical designee as fever. For details, refer to Section 9.1.6.
Instructions will also be provided on how to note the following symptoms/signs in the diary until 
7 days after the prime and boost vaccination (Stage 1 and Stage 2) and the third vaccination 
(Stage 1): 

for preverbal children/infants:
body temperature
vomiting
reduced activity, somnolence, fatigue
irritability/fussiness/crying/screaming
loss of appetite

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
for young children, adolescents, and adults:
body temperature
nausea/vomiting
fatigue/malaise
muscle pain
chills
joint pain
headache
Clinical Laboratory Tests
Samples will be collected for hematology and serum chemistry. 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.
The following tests will be performed by the local laboratory at the time points indicated in the 
Time and Events Schedules unless otherwise specified. 

Hematology Panel
- hemoglobin
- platelet count
- hematocrit
- WBC count with differential
- RBC count

Serum Chemistry Panel 
- AST 
- creatinine
- ALT
Additional clinical laboratory assessments to be performed are as follows:
Urine pregnancy test for sexually active women of childbearing potential before each study 
vaccination (Stage 1 and Stage 2)
Laboratory values will be determined according to the Toxicity Tables for Use in Trials 
Enrolling Healthy Adults (Attachment 4) or the Toxicity Tables for Use in Trials Enrolling 
Children Greater Than 3 Months of Age (Attachment 5).
Any severe (grade 3) non-serious abnormal laboratory values occurring from signing of the ICF 
onwards until 56 days after the boost vaccination in Stage 1 and then again from the day of the 
third vaccination until 28 days after the third vaccination, and from signing of the ICF onwards
until 28 days after the prime vaccination in Stage 2 and then again until 28 days after the boost 
vaccination must be recorded on the adverse event page of the CRF. Thereafter, recording is 
limited to serious adverse events and IREs. All events should be followed to resolution, or until 
reaching a clinically stable endpoint.
Vital Signs
Vital sign measurements (body temperature, heart rate, systolic and diastolic blood pressure) will 
be performed at the time points indicated in the Time and Events Schedules. Blood pressure and 

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heart rate measurements should be preceded by at least 5 minutes of rest in supine position. 
Confirmatory measurements can be performed if inconsistent with a prior measurement. Heart 
rate will be measured manually. Manual blood pressure measurement techniques will be used 
only if an automated device is not available.
Any clinically relevant abnormalities occurring from signing of the ICF onwards until 56 days 
after the boost vaccination in Stage 1 and then again from the day of the third vaccination until
28 days after the third vaccination, and from signing of the ICF onwards until 28 days after the 
prime vaccination in Stage 2 and then again until 28 days after the boost vaccination must be 
recorded on the adverse event page of the CRF. Thereafter, recording will be limited to serious 
adverse events, including deaths and IREs. All events should be followed to resolution, or until 
reaching a clinically stable endpoint.
Physical Examination
A full physical examination (including body length/height and weight) will be carried out at 
screening. At other visits, a brief, symptom-directed examination (including body length/height 
and weight in children aged 12 months up to and including 24 months at the time of the prime 
and the boost vaccination) 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 designated medically-trained clinician. 
Any clinically relevant abnormalities occurring from signing of the ICF onwards until 56 days 
after the boost vaccination in Stage 1 and then again from the day of the third vaccination until 
28 days after the third vaccination, and from signing of the ICF onwards until 28 days after the 
prime vaccination in Stage 2 and then again until 28 days after the boost vaccination must be 
recorded on the adverse event page of the CRF. Thereafter, recording will be limited to serious 
adverse events, including deaths, and IREs. All events should be followed to resolution, or until 
reaching a clinically stable endpoint.
9.4.
Sample Collection and Handling
The actual dates of sample collection must be recorded in the CRF or laboratory requisition 
form. See the Time and Events Schedules for the timing and frequency of all sample collections.
Instructions for the collection, handling, storage, and shipment of safety samples will be 
provided by the local laboratories. 
Instructions for the collection, handling, storage, and shipment of immunogenicity samples will 
be provided in the Laboratory Manual. 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.
SUBJECT COMPLETION/WITHDRAWAL
10.1.
Completion
A subject will be considered to have completed the study if he or she:

Has completed all study assessments on the Day 360 visit (children and adolescents) in 
Stage 2, the Day 360 visit or the 2-year post-prime visit (if applicable) (adults) in Stage 2 or 
on the 36-month post-prime visit or the 1-year post-third vaccination visit (if applicable) in 
Stage 1. 
AND (if applicable)

Has been contacted 1 month post last visit to inquire after their general health status.
Upon completion of the study, sites may offer MenACWY to the Ad26.ZEBOV/MVA-BN-Filo 
arm and the Ad26.ZEBOV/MVA-BN-Filo vaccine (if licensed and/or WHO-prequalified) to the 
control arm upon consultation with the health authorities.
10.2.
Discontinuation of Study Vaccine
If a subject’s study vaccine must be discontinued before the end of the vaccination schedule, this 
will not result in automatic withdrawal of the subject from the study. 
Subjects will be withdrawn from study vaccine administration for the reasons listed below. These 
subjects must not receive any further study vaccine, but should continue to be monitored for 
safety and for immunogenicity if this does not result in a safety risk for the subject.
Pregnancy
Any adverse event considered at least possibly related to study vaccine, worsening of clinical 
status or intercurrent illnesses that, in the opinion of the investigator, requires discontinuation 
from study vaccine
Confirmed EVD
If the randomization code is broken or the treatment allocation has been inadvertently 
revealed at the study site.
Note: Unless the label warrants a second vaccination of MenACWY in the control group.

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10.3.
Contraindications to Vaccination
The following events constitute a contraindication to prime or boost vaccination (Stage 1 and 
Stage 2) or third vaccination (Stage 1). If any of these events occur at the scheduled time for 
vaccination, the subject may be vaccinated within the time window specified in the Time and 
Events Schedules, or be withdrawn from that vaccination at the discretion of the investigator and 
after consultation with the sponsor:
Illness prior to vaccination (this does not include acute illnesses such as diarrhea or mild 
upper respiratory tract infection unless accompanied by body temperature ≥37.5°C in Stage 1 
and 38.0°C in Stage 2).
Fever (body temperature ≥38.0°C) prior to vaccination.
Any fever will be promptly investigated according to national guidelines for the possibility of 
Ebola. For further details, refer to Section 9.1.6.
Note: In case the boost vaccination (Stage 1 and Stage 2) or third vaccination (Stage 1) is 
postponed, the timing of the safety/immunogenicity visits post boost or post-third vaccination 
will be planned relative to the actual vaccination day.
A subject will not be given the boost vaccination (Stage 1 and Stage 2) or third vaccination
(Stage 1) if he or she experiences any of the following events at any time after the prior
vaccinations: 
1. Anaphylaxis clearly attributable to vaccination with study vaccine; OR
2. Generalized urticaria within 72 hours of vaccination considered to be at least possibly related 
to study vaccine; OR
3. A serious adverse event considered to be at least possibly related to study vaccine; OR
4. Injection site ulceration, abscess or necrosis considered to be at least possibly related to the 
study vaccine; OR
5. Any other safety concern threatening the subject’s safety or persisting clinically significant 
abnormality considered to be related to prior vaccinations.
Subjects experiencing any of the events described above must not receive any further study 
vaccine, but should be monitored for safety and for immunogenicity according to the protocol.
10.4.
Withdrawal From the Study
Each subject has the right to withdraw at any time for whatever reason without affecting the right 
to treatment by the investigator. The investigator should make an attempt to contact subjects who 
did not return for scheduled visits or follow-up. Although the subject is not obliged to give 
reason(s) for withdrawing early, the investigator should make a reasonable effort to ascertain the 
reason(s) while fully respecting the subject’s rights.

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A subject will be withdrawn from the study for any of the following reasons:
Repeated failure to comply with protocol requirements
Decision by the sponsor to stop or cancel the study
Decision by the investigator to withdraw subjects
Decision by local regulatory authorities and Institutional Review Board/Independent Ethics 
Committee (IRB/IEC) to stop or cancel the study
Lost to follow-up
Withdrawal of consent
Death
If a subject in Stage 1 or Stage 2 is lost to follow-up, every reasonable effort must be made by 
the study site personnel to contact the subject and to determine the reason for 
discontinuation/withdrawal. The measures taken for at least 3 efforts to follow-up must be 
documented. No additional subjects will be enrolled in case a subject withdraws after the prime 
vaccination. 
If a subject withdraws prematurely from the study, early withdrawal assessments should be 
obtained (see Section 9.1.7). When a subject withdraws before completing the study, the reason 
for withdrawal should be documented in the CRF and in the source document. 
A subject who wishes to withdraw consent from participation in the study will be offered an 
optional visit for safety follow-up (before formal withdrawal of consent). The subject has the 
right to refuse. 
Withdrawal From the Use of Samples in Future Research
Subjects in Stage 1 and 2 may withdraw consent for use of 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.
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. Full details will be provided in the Statistical Analysis Plan (SAP) which will be 
developed by the sponsor in collaboration with the London School of Hygiene & Tropical 
Medicine. The SAP will be finalized and signed off and submitted for review to the appropriate 
regulatory authorities before the first subject will be vaccinated in Stage 1.
The primary analysis of immunogenicity and safety in Stage 1 will be performed when all 
subjects have completed the study or have discontinued earlier. In Stage 2, primary analyses will 
be performed for adults (≥18 years) and children (≥1 to 17 years) when these respective groups
complete the study or subjects have discontinued earlier. One primary analysis for all children is 

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planned, presenting the data by age group (12 to 17 years, 4 to 11 years, 1 to 3 years, inclusive). 
Interim analyses may be performed during the study per age group (ie, ≥18 years, 12 to 17 years, 
4 to 11 years, 1 to 3 years, inclusive) for the purpose of informing future program-related 
decisions or for regulatory purposes in a timely manner (see Section 11.6).
The analysis of immunogenicity and safety are further discussed in Sections 11.4 and 11.5,
respectively.
11.1.
Analysis Sets
The Safety analysis set will include all subjects who received at least one study vaccination. Data 
will be shown by treatment group (as treated).
The Per Protocol Immunogenicity analysis set includes all randomized (for Stage 2) and 
vaccinated subjects from any stage who fulfill the following criteria:
-
who received the prime and boost vaccination,
-
who have data from baseline and at least one post-vaccination immunogenicity blood 
draw,
-
who have no major protocol violations or did not receive a delayed boost vaccination due 
to a pause that could affect the immune response.
The Per Protocol Immunogenicity analysis set is the primary analysis population for 
immunogenicity analyses.
11.2.
Subject Information
For each analysis set, demographic characteristics (eg, age and sex) and screening/baseline 
characteristics (eg, physical examination, medical history) will be tabulated and summarized 
with descriptive statistics for the vaccinated group and the control group (Stage 2 only).

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11.3.
Sample Size Determination
Safety
Table 4 shows the number of subjects planned for safety and immunogenicity by age group for 
Stage 1 and Stage 2. 
Table 4:
Number of Subjects Planned per Stage and Population for Safety 
and Immunogenicity Assessments
Safety and Immunogenicity Data
Stage 1
Stage 2
Population Age
(years inclusive)
Ebola vaccinea
Ebola vaccineb
Active controlc
Adults (≥18 years)
40
300
100
12 to 17 years
-
144
48
4 to 11 years
-
144
48
1 to 3 years
-
144
48
Total
40
732
244
a
Prime-boost regimen of Ad26.ZEBOV followed by MVA-BN-Filo (boost vaccination)
and Ad26.ZEBOV (third vaccination).
b
Prime-boost regimen of Ad26.ZEBOV followed by MVA-BN-Filo.
c
The active control will consist of the WHO-prequalified MenACWY vaccine.
As shown in Table 5 below, the sample sizes selected indicate that the probability of observing at 
least 1 (serious) adverse event occurring at a rate of 1/10 or more in each group (Stage 1; adults, 
Stage 2; adults, 12-17 years, 4-11 years, and 1-3 years) is ≥99%. The probability of observing at 
least 1 (serious) adverse event occurring at a rate of 1/100 is 95% with 300 subjects. The 
probability of observing at least 1 (serious) adverse event occurring at a rate of 1/1,000 is 26% 
with 300 subjects and 52% with 732 subjects. If no events are observed during Stage 2 for a 
specific adverse event, then the Bayesian posterior probability that the event rate is below 
1/1,000 equals 41% for 144 subjects (ie, the number of children in each age group), 56% for 
300 subjects (ie, the number of adults), and 77% with 732 subjects when using Jeffreys’ prior.
Table 5:
Probability of Observing at Least One (Serious) Adverse Event
N
Probability of observing at least one (serious) adverse event when incidence equals
1/10
1/100
1/1,000
40
99%
33%
4%
144
100%
76%
13%
300
100%
95%
26%
732
100%
100%
52%
Table 6 represents the 95% upper limit for the true proportion for various sample sizes associated 
with no reported (serious) adverse events. For example when 40 subjects are vaccinated, the 
observation of 0 reactions would be associated with a 95% confidence that the true rate is less 
than 7.2%.

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Table 6:
Sample Size Justification Safety Evaluation in Stage 1 and 2
N
95% upper limit for the true proportion of a (serious) adverse reaction when no events are reported
40
7.2%
144
2.1%
300
1.0%
732
0.4%
Immunogenicity
As part of Amendment 5, the number of children in each age group was doubled to compensate 
for an expected higher variability in immunogenicity parameters. 
11.4.
Immunogenicity Analyses
All subjects in the Per Protocol Immunogenicity analysis set as defined in Section 11.1 will be 
included in the analysis.
Descriptive statistics (actual values, changes from baseline, if applicable) will be calculated for 
continuous immunologic parameters at all time points analyzed. Geometric mean concentrations 
and/or titers and changes together with a corresponding 95% confidence interval will be 
calculated. Graphical representations of changes in immunologic parameters will be prepared, as 
applicable. Frequency tabulations will be calculated for discrete (qualitative) immunologic 
parameters at all time points and response analyses will be performed. Different definitions of 
immunologic response will be further detailed in the SAP.
In addition, a longitudinal data analysis of the immunogenicity response over time will be 
explored. Least square means with their 95% confidence intervals will be calculated from this 
model. 
11.5.
Safety Analyses
No formal statistical testing of safety data is planned. Safety analysis will be performed on the 
safety analysis set. Data from Stage 1 will be summarized separately. Safety data from Stage 2 
will be shown by treatment group (as treated), and by age group. 
Safety data will be analyzed descriptively (including 95% confidence intervals, if applicable) for 
subjects receiving control or active vaccine. 
Baseline for all safety parameters will be defined as the last value before the prime vaccination.
For Stage 1 and 2, the following summaries are planned:
Adverse Events (Including Reactogenicity)
The verbatim terms used in the CRF by investigators to report adverse events will be coded using 
the Medical Dictionary for Regulatory Activities (MedDRA). All reported adverse events 
(solicited local, solicited systemic, and unsolicited) during the treatment period (ie, treatment-
emergent adverse events, and adverse events that have worsened since baseline) will be included 
in the analysis. For each adverse event, the number and percentage of subjects who experience at 

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least one occurrence of the given event will be summarized. Summaries, listings, datasets and/or 
subject narratives may be provided as appropriate, for those subjects who die, discontinue study 
vaccinations due to an adverse event, or experience a severe or serious adverse event. The 
analysis of solicited and unsolicited adverse events will be done based on the safety analysis set. 
Clinical Laboratory Tests
Laboratory abnormalities will be determined according to the toxicity grading tables in 
Attachment 4 and Attachment 5, and in accordance with the normal ranges of the clinical 
laboratory. 
The worst laboratory abnormalities following vaccination will be tabulated.
Vital Signs 
Vital signs abnormalities following vaccination will be tabulated by worst abnormality grade.
Physical Examination
Physical examination abnormalities following vaccination will be tabulated by worst abnormality 
grade. BMI will be calculated using the recording of height at screening. Body weight and BMI 
results will be tabulated descriptively.
For children, weight and height for adequacy of growth milestones percentiles will be calculated 
using the recording of those measurements at screening (baseline) compared to study 
progression/visits. Percentile results (according to local growth charts) will be tabulated 
descriptively.
11.6.
Interim Analysis
Interim analyses may be performed during the study for the purpose of informing future 
program-related decisions and for regulatory purposes in a timely manner.
11.7.
Independent Data Monitoring Committee (IDMC) 
An IDMC will be established to monitor safety data on an ongoing basis to ensure the continuing 
safety of the subjects enrolled in this study.
The IDMC will consist of at least one medical expert in the relevant therapeutic area and at least 
one statistician.
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 SAP. Additional reviews can be requested by the IDMC.
A schematic presentation of the IDMC schedule is provided in Attachment 1.

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11.7.1.
Safety
The IDMC will review all available 7-day post-prime safety data (including clinical laboratory 
results) before the first subject of the current cohort will receive the boost: 

In Stage 1 to determine whether:

the boost vaccination in Stage 1 can be initiated, and

the prime vaccination in Stage 2 (subjects aged 12 to 17 years inclusive) can be 
initiated.

In Stage 2 (subjects aged 12 to 17 years inclusive) to determine whether:

the boost vaccination in subjects aged 12 to 17 years inclusive can be initiated, and

the prime vaccination of subjects aged 4 to 11 years inclusive can be initiated.

In Stage 2 (subjects aged 4 to 11 years inclusive) to determine whether:

the boost vaccination in subjects aged 4 to 11 years inclusive can be initiated, and 

the prime vaccination of subjects aged 1 to 3 years inclusive can be initiated.

In Stage 2 (subjects aged 1 to 3 years inclusive) to determine whether:

the boost vaccination in subjects aged 1 to 3 years inclusive can be initiated. 
The IDMC will also review all cumulative safety data including the 7-day post-boost safety data 
(including clinical laboratory results) to determine if the boost vaccination in the next stage 
and/or next age group can be given. An IDMC meeting will therefore take place with all 
available data (also including the 7-day post-prime safety data within that age group) before 
boost vaccination will be administered.
A schematic presentation of the IDMC schedule is provided in Attachment 1.
11.8.
Clinical Steering Committee and Management Committee
Oversight of the study will be conducted by the Trial Management Team which will consist of 
members from Janssen (the sponsor), as well as key collaborators from the participating 
countries. This Trial Management Team will be responsible for protocol development and 
ensuring proper study execution, subject to the approval of the Clinical Steering Committee.
The Clinical Steering Committee will have the final say on all matters relating to the study, to the 
extent that a decision could not be taken at a lower level. 
11.9.
Pausing Rules
The investigators and the sponsor’s medical monitor will review the safety of enrolled subjects 
on an ongoing basis. The sponsor’s medical monitor will be involved in all discussions and 
decisions (see Section 12.4).
If any of the events described in Section 11.9.1 occur in any subject who received at least one 
dose of study vaccine in the study (at any site), that site investigator will halt the vaccination of 
further subjects and the sponsor’s medical monitor will be notified immediately. The sponsor’s 

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medical monitor will then also inform all the other investigators to halt further vaccination as 
well. 
For the events described below, the sponsor’s medical monitor notifies the IDMC immediately. 
Within 3 business days, the IDMC will convene to review the available safety data as outlined in 
the charter and to discuss study suspension or discontinuation of further vaccination or to decide 
that vaccination may resume. The sites will be allowed to resume activities upon receipt of a 
written notification from the sponsor. The pausing rules will be re-set each time and the same 
criteria have to be met to halt further vaccination again. The communications from the IDMC 
will be forwarded by the investigator to the IEC/IRB according to local standards and regulations 
and by the sponsor to the relevant health authorities.
11.9.1.
Stage 1 
1.
Death in any subject considered to be at least possibly related to the study vaccine; OR
2.
An anaphylactic reaction within 24 hours of vaccination or the presence of generalized 
urticaria within 72 hours of vaccination in any subject considered to be at least possibly 
related to the study vaccine; OR
3.
A life-threatening or other serious adverse event in any subject considered to be at least 
possibly related to the study vaccine.
If any of the following events occur in subjects who received at least one dose of study vaccine 
in the study (across all sites), the sponsor’s medical monitor will notify all investigators to halt 
vaccination of further subjects.
4.
Three or more subjects experience a severe (grade 3) (non-serious) unsolicited adverse event 
(of the same type) considered to be related to any of the study vaccines that persists for 3 or 
more days; OR
5.
Three or more subjects experience a persistent (upon repeat testing) severe (grade 3) (non-
serious) abnormality (including unexplained hematuria) related to the same laboratory 
parameter and considered to be related to any of the study vaccines; OR
6.
Three or more subjects experience the same severe (grade 3) (non-serious) solicited 
systemic reaction considered to be related to any of the study vaccines that persists for 3 or 
more days (subjective systemic reaction corroborated by study personnel).
11.9.2.
Stage 2
11.9.2.1.
Adults and Adolescents (Aged ≥12 Years)
1.
Death in any subject considered to be at least possibly related to the study vaccine; OR
2.
An anaphylactic reaction within 24 hours of vaccination or the presence of generalized 
urticaria within 72 hours of vaccination in any subject considered to be at least possibly 
related to the study vaccine; OR
3.
A life-threatening or other serious adverse event in any subject considered to be at least 
possibly related to the study vaccine.

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11.9.2.2.
Children (Aged ≥1 to 11 Years, Inclusive)
1.
Death in any subject considered to be at least possibly related to the study vaccine; OR
2.
An anaphylactic reaction within 24 hours of vaccination or the presence of generalized 
urticaria within 72 hours of vaccination in any subject considered to be at least possibly 
related to the study vaccine; OR
3.
A life-threatening or other serious adverse event in any subject considered to be at least 
possibly related to the study vaccine.
If any of the following events occur in subjects within the same age group (≥1-3 years OR 
≥4-11 years) who received at least one dose of study vaccine in the study (across all sites), the 
sponsor’s medical monitor will notify all investigators to halt vaccination of further subjects.
4.
Three or more subjects experience a severe (grade 3) (non-serious) unsolicited adverse event 
(of the same type) considered to be related to any of the study vaccines that persists for 3 or 
more days.
5.
Three or more subjects experience a persistent (upon repeat testing) severe (grade 3) (non-
serious) abnormality (including unexplained hematuria) related to the same laboratory 
parameter and considered to be related to any of the study vaccines; OR
6.
Three or more subjects experience the same severe (grade 3) (non-serious) solicited 
systemic reaction considered to be related to any of the study vaccines that persists for 3 or 
more days (subjective systemic reaction corroborated by study personnel.) 
12.
ADVERSE EVENT REPORTING
Timely, accurate, and complete reporting and analysis of safety information from clinical studies 
are crucial for the protection of subjects, investigators, and the sponsor, and are mandated by 
regulatory agencies worldwide. 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.
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 subject administered a 
medicinal (investigational or non-investigational) product. An adverse event does not necessarily 
have a causal relationship with the treatment. 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 to that medicinal (investigational or non-investigational) product. (Definition per 
International Council for Harmonisation [ICH].)

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This includes any occurrence that is new in onset or aggravated in severity or frequency from the 
baseline condition, or abnormal results of diagnostic procedures, including laboratory test 
abnormalities.
Note: The sponsor collects adverse events starting with the signing of the ICF (refer to 
Section 12.3.1 for time of last adverse event recording).
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 subject 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 (except the vaccine virus vectors 
themselves) 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 subject 
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 vaccine and the event (eg, death from anaphylaxis), the event 
must be reported as a suspected unexpected serious adverse reaction (SUSAR) (even after the 
study is over, if the sponsor, IDMC or investigator becomes aware of them).
Should any study subject develop EVD during the study period, this event will be captured as a 
serious adverse event.
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 for MVA-BN-Filo, the 
expectedness of an adverse event will be determined by whether or not it is listed in the 
respective Investigator’s Brochures and Addenda, if applicable.8,9 For MenACWY, refer to the 
applicable vaccine prescribing information.

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Adverse Event Associated With the Use of the Vaccine
An adverse event is considered associated with the use of the study vaccine if the attribution is 
possible, probable, or very likely by the definitions listed in Section 12.1.2.
An adverse event is considered not associated with the use of the study vaccine if the attribution 
is not related or doubtful by the definitions listed in Section 12.1.2.
Immediate Reportable Events
The following list of neuroinflammatory disorders are categorized as IREs, and should be 
reported to the sponsor within 24 hours of becoming aware of the event using the IRE Form. 
Relevant data from the IRE Form will be captured in the clinical database.

Cranial nerve disorders, including paralyses/paresis (eg, Bell’s palsy) 

Optic neuritis

Multiple sclerosis

Transverse myelitis

Guillain-Barré syndrome, including Miller Fisher syndrome, Bickerstaff’s encephalitis and 
other variants

Acute disseminated encephalomyelitis, including site-specific variants: eg, non-infectious 
encephalitis, encephalomyelitis, myelitis, myeloradiculomyelitis

Myasthenia gravis and Lambert-Eaton myasthenic syndrome 

Immune-mediated 
peripheral 
neuropathies 
and 
plexopathies 
(including 
chronic 
inflammatory 
demyelinating 
polyneuropathy, 
multifocal 
motor 
neuropathy 
and 
polyneuropathies associated with monoclonal gammopathy)

Narcolepsy

Isolated paresthesia of >7 days duration
Symptoms, signs or conditions which might (or might not) represent the above diagnoses, should 
be recorded and reported as IREs 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 as soon as they 
become available.
If the IRE is also serious (serious adverse event), it will be reported using the same process as for 
other serious adverse events.
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 vaccine or to alternative causes 
(eg, natural history of an underlying diseases, concomitant therapies). This applies to all adverse 
events, whether serious or non-serious.

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Symptoms of local adverse events (injection site reactions) will be considered as related to the 
study vaccine. For all other adverse events, the investigator will use the following guidelines to 
assess the causal relationship to study vaccine:
Not Related
An adverse event that is not related to the use of the vaccine.
Doubtful
An adverse event for which an alternative explanation is more likely, eg, concomitant drug(s), 
concomitant disease(s), or the relationship in time suggests that a causal relationship is unlikely.
Possible
An adverse event that might be due to the use of the vaccine. An alternative explanation, 
eg, concomitant drug(s), concomitant disease(s), is inconclusive. The relationship in time is 
reasonable; therefore, the causal relationship cannot be excluded.
Probable
An adverse event that might be due to the use of the vaccine. The relationship in time is 
suggestive (eg, confirmed by dechallenge). An alternative explanation is less likely, 
eg, concomitant drug(s), concomitant disease(s).
Very Likely
An adverse event that is listed as a possible adverse reaction and cannot be reasonably explained 
by an alternative explanation, eg, concomitant drug(s), concomitant disease(s). The relationship 
in time is very suggestive.
12.1.3.
Severity Criteria
Adverse events and laboratory data will be coded for severity using the toxicity grading tables in 
Attachment 4 and Attachment 5. 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
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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12.2.
Special Reporting Situations
Safety events of interest on a sponsor study drug or vaccine that may require expedited reporting 
and/or safety evaluation include, but are not limited to:

Overdose of a sponsor study vaccine

Inadvertent or accidental exposure to a sponsor study vaccine 

Medication error involving a sponsor product (with or without subject/patient exposure to 
the sponsor study vaccine, eg, name confusion)

IREs
Special reporting situations should be recorded in the CRF. For reporting of IREs, refer to 
Section 12.3.3. 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
All adverse events and special reporting situations, whether serious or non-serious, will be 
reported from the time a signed and dated ICF is obtained until 56 days after the boost
vaccination in Stage 1 and then again from the day of the third vaccination until 28 days after the 
third vaccination, and until 28 days after the prime vaccination in Stage 2 and then again until 
28 days after the boost vaccination. Subjects in Stage 1 and Stage 2 will also record symptoms of 
solicited local and systemic adverse events in the diary in the evening after the prime and boost
vaccination and after the third vaccination (Stage 1 only) and then daily for the next 7 days.
Serious adverse events, including deaths, and IREs will be followed-up until the subject’s last 
study visit.
Serious adverse events must be reported using the Serious Adverse Event Form. SUSARs will be 
reported even after the study is over, if the sponsor, the IDMC or the investigator becomes aware 
of them.
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 vaccine. All adverse events will be deemed 
related to study vaccine or not related to study vaccine, 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.

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All adverse events, regardless of seriousness, severity, or presumed relationship to study vaccine, 
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 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. For reporting of IREs, refer to Section 12.3.3.
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 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 
(Stage 2 only). Participating investigators and IEC/IRB will receive a blinded SUSAR summary, 
unless otherwise specified.
Subjects will be provided with a wallet card and instructed to carry this card with them for the 
duration of the study indicating the following:

Study number

Statement, in the local language(s), that the subject is participating in a clinical study

Investigator's name and 24-hour contact telephone number

Sponsor's name and 24-hour contact telephone number (for medical staff only)

Subject number

Information about who should be contacted in case of emergency

Any other information that is required to do an emergency breaking of the blind (Stage 2)

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 24 hours of their knowledge of the event. All 
serious adverse events will be reported in accordance with local regulations. 
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 provided according to the sponsor’s instructions.
All serious adverse events that have not resolved by the end of the study, or that have not 
resolved upon discontinuation of the subject's participation in the study, must be followed until 
any of the following occurs:

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
The event resolves

The event stabilizes

The event returns to baseline, if a baseline value/status is available

The event can be attributed to agents other than the study vaccine or to factors unrelated to 
study conduct

It becomes unlikely that any additional information can be obtained (subject 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 subject, whether or not the event is expected or 
associated with the study vaccine, is considered a serious adverse event.
12.3.3.
Immediate Reportable Events
Immediate Reportable Events
One subject in the study VAC52150EBL2001 experienced a serious and very rare condition 
called “Miller Fisher syndrome”. This condition consists of double vision, pain on moving the 
eye, and difficulty with balance while walking. Miller Fisher syndrome most commonly occurs 
following a recent infection. The subject experienced these symptoms about a week after 
suffering from a common cold and fever. The event happened about a month after boost 
vaccination with either MVA-BN-Filo or placebo. This subject had to go to the hospital for 
treatment and has recovered. After an extensive investigation, the event has been considered to 
be doubtfully related to vaccine and most likely related to the previous common cold.
Any events of neuroimmunologic significance (listed below) should be categorized as IREs and 
should be reported throughout the study using the IRE Form provided within 24 hours to the 
sponsor. Events suggestive of the disorders considered IREs should be reported even if the final 
diagnosis has not been yet determined, and follow-up information and final diagnosis should be 
submitted to the sponsor as soon as they become available.
If an event meets criteria for serious adverse events (see above), it should be documented as such 
using the Serious Adverse Event form, as well as the relevant CRF Adverse Event page and the 

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complete IRE Form per the instructions to be included as part of the Serious Adverse Event
report.
12.3.4.
Pregnancy
All initial reports of pregnancy must be reported to the sponsor by the study-site personnel
within 24 hours of their knowledge of the event using the appropriate pregnancy notification 
form. Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered serious adverse events and must be reported using 
the Serious Adverse Event Form. Any subject who becomes pregnant during the study must be 
promptly withdrawn from further study vaccination but should continue participation in the study 
for follow-up of safety and immunogenicity if this does not result in a safety risk for the subject. 
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required.
Pregnancy outcomes from all female subjects who became pregnant during the study until up to 
28 days after the boost vaccination or 3 months after the prime vaccination (whichever is longer) 
as well as from those who became pregnant between at least 14 days before until up to 3 months 
after the third vaccination may be collected in the current study or in the VAC52150EBL3005
long-term follow-up study for subjects who consent to this. Children born to these female 
subjects may be enrolled in VAC52150EBL3005 study and followed for 5 years if the parent 
consents to this.
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 on 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 subjects, 
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.

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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.
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 on the Contact Information page(s), which will be 
provided as a separate document.
14.
STUDY VACCINE INFORMATION
14.1.
Description of Study Vaccines
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.8
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 (CEF) 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.9
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 SPC 
for a list of excipients. 

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14.1.4.
Placebo 
The placebo supplied for this study will be formulated as a sterile 0.9% saline for injection (as 
commercially available).
14.2.
Packaging and Labeling
All study vaccines will be manufactured and packaged in accordance with Good Manufacturing 
Practice (GMP). All study vaccines will be packaged and labeled under the responsibility of the 
sponsor. No study vaccine can be repacked or relabeled without prior approval from the sponsor.
Further details for study vaccine packaging and labeling can be found in the Site Investigational 
Product Procedures Manual.
14.3.
Preparation, Handling and Storage 
Study vaccine 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 (including refrigerators, freezers) must be equipped with a continuous 
temperature monitor and alarm, and with back-up power systems. In the event that study vaccine 
is exposed to temperatures outside the specified temperature ranges, all relevant data will be sent 
to the sponsor to determine if the affected study vaccine can be used or will be replaced. The 
affected study vaccine must be quarantined and not used until further instruction from the 
sponsor is received.
A pharmacist/qualified staff member will prepare all doses for vaccine administration and provide 
it for dispensing. Blinding in Stage 2 will be achieved by preparation of study vaccine by 
unblinded qualified study-site personnel not involved in any other study-related procedures, and 
by the administration of vaccine in a masked syringe in a way that maintains double-blinding.
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 (for Stage 2 only).
14.4.
Vaccine Accountability
The investigator is responsible for ensuring that all study vaccine received at the site is 
inventoried and accounted for throughout the study. The study vaccine administered to the 
subject must be documented on the study vaccine accountability form. All study vaccine will be 
stored and disposed of according to the sponsor’s instructions. Study-site personnel must not 
combine contents of the study vaccine containers. 
Study vaccine must be handled in strict accordance with the protocol and the container label, and 
must be stored at the study site in a limited-access area or in a locked cabinet under appropriate 
environmental conditions. Unused study vaccine must be available for verification by the 
sponsor’s study site monitor during on-site monitoring visits. The return to the sponsor of unused 

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study vaccine will be documented on the Investigational Product Destruction Form. When the 
study site is an authorized destruction unit and study vaccine supplies are destroyed on-site, this 
must also be documented on the Investigational Product Destruction Form. 
Potentially hazardous materials, such as used needles, syringes, empty vials, and vials containing 
hazardous liquids, should be disposed of immediately in a safe manner and therefore will not be 
retained for study vaccine accountability purposes.
Study vaccine will be dispensed under the supervision of the investigator or qualified member of 
the study-site personnel, or by the pharmacist/qualified staff member. Study vaccine will be 
supplied only to subjects participating in the study. Study vaccine may not be reassigned for use 
by other subjects. Applying additional labels can only be done on the authority of the sponsor. 
The investigator agrees neither to dispense the study vaccine from, nor store it at, any site other 
than the study sites agreed upon with the sponsor.
15.
STUDY-SPECIFIC MATERIALS
The investigator will be provided with the following supplies:

Investigator Brochures and Addendum (if applicable) for Ad26.ZEBOV and MVA-BN-Filo

Site Investigational Product Procedures Manual and Site Blinding Plan (for Stage 2 only)

Laboratory Manual

Algorithm for evaluation of fever

Interactive Voice/Web Response System (IVRS/IWRS) Manual (Stage 1 third vaccination 
and Stage 2)

Electronic Data Capture (eDC) Manual/electronic CRF Completion Guidelines

Deployment and Compliance manual

Sample ICF

Subject diaries

TOU

Rulers, thermometers

Recruitment tools, as applicable

Subject wallet card
16.
ETHICAL ASPECTS
16.1.
Study-Specific Design Considerations
Potential subjects will be fully informed of the risks and requirements of the study and, during 
the study, subjects will be given any new information that may affect their decision to continue 
participation. They will be told that their consent to participate in the study is voluntary and may 
be withdrawn at any time with no reason given and without penalty or loss of benefits to which 

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they would otherwise be entitled. Only subjects who are fully able to understand the risks, 
benefits, and potential adverse events of the study, and provide their consent voluntarily will be 
enrolled.
When referring to the signing of the ICF, the terms legal guardian and legally acceptable 
representative refer to the traditionally or legally appointed guardian of the child with authority 
to authorize participation in research. For each subject, his or her parent(s) (preferably both 
parents, if available) or a 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. 
Assent must be obtained from children (minors) capable of understanding the nature of the study, 
typically subjects 7 years of age and older, depending on the institutional policies. For the 
purposes of this study, all references to subjects who have provided consent (and assent as 
applicable) refers to the subjects and his or her parent(s) or the subject's legal guardian(s) or 
legally acceptable representative(s) who have provided consent according to this process. Minors 
who assent to a study and later withdraw that assent should not be maintained in the study 
against their will, even if their parents still want them to participate. For details of the consent 
procedures in this study, refer to Section 16.2.3.
The total blood volume to be collected is expected to be approximately between 28.1 and 
164.4 mL, depending on the stage of the study, and the age of the subject. Details are provided in 
the Time and Events Schedules. 
Test of Understanding
The TOU is a short assessment of the subject’s understanding of key aspects of the study. The 
test will help the study staff to determine how well the subject understands the study and the 
requirements for participation.
The TOU must be completed by all subjects participating in Stage 1 and Stage 2, prior to 
enrollment into the study and after reading but before signing the ICF. For children, the TOU 
will be administered to the parent or guardian from whom consent is sought. If both the parent or 
guardian and the child will be enrolled in the study, the parent/guardian will need to complete the 
TOU twice (ie, one for the parent/guardian and one for the child). In case the parent/guardian 
consents for multiple children of the same family, the TOU needs to be completed only once, ie, 
for the first child of the family enrolled in the study. In case the TOU information would change 
while recruiting multiple children of the same family, the TOU should be completed again for 
the first child of the family that was enrolled after the TOU change had occurred. The TOU is 
reviewed one-on-one with the subject and a member of the study team. Subjects in Stage 2 are 
allowed to retake the test twice to achieve the passing score (≥90%) required for participation in 
the study. If a subject fails to achieve the passing score, further information and counseling will 
be provided by the study team member. 
Any subject not capable of understanding the key aspects of the study, and their requirements for 
participation, should not be enrolled.

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16.2.
Regulatory Ethics Compliance
16.2.1.
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the 
protocol, current ICH guidelines on GCP, and applicable regulatory and country-specific 
requirements.
Good Clinical Practice is an international ethical and scientific quality standard for designing, 
conducting, recording, and reporting studies that involve the participation of human 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

Subject diaries

TOU

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), 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:

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
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 study at intervals stipulated in guidelines of the IEC/IRB (at 
least annually)

Reports of adverse events that are serious, unlisted/unexpected, and associated with the 
study vaccine

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. The 
reapproval should be documented in writing (excluding the ones that are purely administrative, 
with no consequences for subjects, data, or study conduct).
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
In this community-based, study, informed consent will take place at several levels ranging from 
approval from the government authorities, followed by community engagement, and finally, 
individual consent.
Approval from Respective Authorities 
Approval for this project will be obtained from the respective healthcare authorities in the 
country where the study is conducted. 

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Additionally, during the planning process of the study approval will be sought from other 
authorities such as district or local councilors, political leaders, and traditional leaders. 
Engagement at the Community Level
Documented community engagement by a community leader must be available.
Consent at the Individual Level 
Consent at the individual level will be sought from all subjects who participate in Stage 1 and 
Stage 2.
Each subject (or a legally acceptable representative) must give written consent according to local 
requirements after the nature of the study has been fully explained. The ICF(s) must be signed 
before performance of any study-related activity. The ICF(s) that is/are used must be approved 
by both the sponsor and by the reviewing IEC/IRB and be in a language that the subject can 
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 potential subjects or their legally acceptable representatives the aims, 
methods, reasonably anticipated benefits, and potential hazards of the study, and any discomfort 
participation in the study may entail. Subjects will be informed that their participation is 
voluntary and that they may withdraw consent to participate at any time. They will be informed 
that choosing not to participate will not affect the care the subject will receive for the treatment 
of his or her disease. Finally, they will be told that the investigator will maintain a subject 
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 subject, to the extent permitted by the applicable law(s) or regulations. By 
signing the ICF the subject or legally acceptable representative is authorizing such access, 
including permission to obtain information about his or her survival status, and agrees to allow 
his or her study physician to recontact the subject for the purpose of obtaining consent for 
additional safety evaluations, if needed.
The subject or 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 either the subject's or his or her legally acceptable 
representative's personally dated signature. After having obtained the consent, a copy of the ICF 
must be given to the subject.
For subjects in Stage 1 and Stage 2, a TOU will be administered after reading but before signing 
the ICF, to assess the subject’s understanding of key aspects of the study. 
Children (minors) or subjects who are unable to comprehend the information provided can be 
enrolled only after obtaining consent of a legally acceptable representative. Assent must be 

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obtained from children (minors) capable of understanding the nature of the study, typically 
subjects 7 years of age and older, depending on the institutional policies. The assent procedure 
must be witnessed by an adult literate parent/legal guardian/third party not involved in the 
conduct of the study, and documented. 
Subjects enrolled in this study as minors and who are still actively participating in the study 
when they turn 18 years old will need to consent as adults for further participation in the study. 
Consenting will occur at the next available opportunity (ie, next study visit, contact point, 
intervention, etc) upon reaching majority. Similarly, subjects who turn 7 years old and who are 
still actively participating in the study will be requested to give a positive assent. 
16.2.4.
Privacy of Personal Data
The collection and processing of personal data from subjects enrolled in this study will be 
limited to those data that are necessary to 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 subject (or his or her legally acceptable representative) 
includes explicit consent for the processing of personal data and for the investigator/institution to 
allow direct access to his or her original medical records (source data/documents) for study-
related monitoring, audit, IEC/IRB review, and regulatory inspection. This consent also 
addresses the transfer of the data to other entities and to other countries with similar privacy 
protection security.
The subject has the right to request through the investigator access to his or her personal data and 
the right to request rectification of any data that are not correct or complete. Reasonable steps 
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 
Each subject in Stage 1 and 2 will be asked to consent voluntarily for their blood samples to be 
stored for other research studies that may be done after this study is completed. Subjects 
unwilling to have their blood samples stored for future use, can participate in the 

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immunogenicity assessments without having their blood samples stored for future testing (see 
also Section 10.4). 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.
17.
ADMINISTRATIVE REQUIREMENTS
17.1.
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 change(s) involves only logistic or administrative aspects of the study, the 
IRB (and IEC 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 (see Contact Information page(s) provided separately). 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.
17.2.
Regulatory Documentation
17.2.1.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities 
in each respective country, if applicable. A study may not be initiated until all local regulatory 
requirements are met.
17.2.2.
Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study vaccine to 
the study site:

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
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

Any other documentation required by local regulations
The following documents must be provided to the sponsor before enrollment of the first subject:

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
17.3.
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 subject identification and enrollment log will be treated as confidential and will be filed by 
the investigator in the study file. To ensure subject confidentiality, no copy will be made. All 
reports and communications relating to the study will identify subjects by subject identification
and date of birth.
The investigator must also complete a subject screening log, which reports on all subjects who 
were seen to determine eligibility for inclusion in the study. 

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17.4.
Source Documentation
At a minimum, source documentation must be available for the following to confirm data 
collected in the CRF: subject identification, eligibility, and study identification; study discussion 
and date of signed informed consent; dates of visits; date of vaccination, results of safety 
parameters as required by the protocol; record of all solicited and unsolicited adverse events and 
follow-up of adverse events; concomitant medication; vaccine receipt/dispensing/return records; 
study vaccine administration information; and date of study completion and reason for early 
discontinuation of study vaccine or withdrawal from the study, if applicable. 
In addition, the author of an entry in the source documents should be identifiable.
At a minimum, the type and level of detail of source data available for a subject should be 
consistent with that commonly recorded at the study site as a basis for standard medical care. 
Specific details required as source data for the study will be reviewed with the investigator 
before the study and will be described in the monitoring guidelines (or other equivalent 
document).
The subject diary and TOU for subjects in Stage 1 and Stage 2 will be considered source 
documents. 
Information from the diary provided to subjects to record symptoms of solicited local and 
systemic adverse events until 7 days after the prime and boost vaccination (Stage 1 and Stage 2) 
and after the third vaccination (Stage 1), will be reviewed by the investigator or clinical designee 
to transcribe into the relevant parts of the CRF as described in the CRF Completion Guidelines.
Inclusion and exclusion criteria not requiring documented medical history must be verified at a 
minimum by subject interview or other protocol required assessment (eg, physical examination, 
laboratory assessment) and documented in the source documents.
17.5.
Case Report Form Completion
Case report forms are planned to be provided for each subject in electronic format. 
Electronic Data Capture (eDC) will be used for this study. The study data will be transcribed by 
study-site personnel from the source documents onto an electronic CRF or entered directly into 
the electronic CRF which then serves as source data, and transmitted in a secure manner to the 
sponsor within the timeframe agreed upon between the sponsor and the study site. The electronic 
file will be considered to be the CRF.
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 documentation. All data relating to the 
study must be recorded in CRFs prepared by the sponsor. Data must be entered into CRFs in 
English. Study site personnel must complete the CRF as soon as possible after a subject visit, and 
the forms should be available for review at the next scheduled monitoring visit.

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All subjective measurements (eg, pain scale information or other questionnaires) will be 
completed by the same individual who made the initial baseline determinations whenever 
possible. The investigator must verify that all data entries in the CRFs are accurate and correct.
All CRF entries, corrections, and alterations must be made by the investigator or other authorized 
study-site personnel. 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 
3 different ways:

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).

Study site manager can generate a query for resolution by the study-site personnel.

Clinical data manager can generate a query for resolution by the study-site personnel. 
17.6.
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 CRFs for accuracy and completeness during on-site monitoring visits 
and after transmission to the sponsor; any discrepancies will be resolved with the investigator or 
designee, as appropriate. After upload of the data into the study database they will be verified for 
accuracy and consistency with the data sources. 
17.7.
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all CRFs 
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.

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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.
17.8.
Monitoring
The sponsor will perform study site visits to monitor this study.
The sponsor will perform on-site monitoring once a month or 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 for Stage 1 and
Stage 2 has begun. At these visits, the monitor will compare the data entered into the CRFs with 
the vaccination unit and/or clinic records (source documents). 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 documentation (medical records) must be allowed for the purpose of 
verifying that the data recorded in the CRF are consistent with the original source data. Findings 
from this review of CRFs and source documents will be discussed with the study-site personnel. 
The sponsor expects that, during monitoring visits, the relevant study-site personnel will be 
available, the source documentation 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 Stage 2, there will be independent monitoring of the pharmacy and preparation of study 
vaccines by an unblinded monitor (independent study vaccine monitor); regular monitors will be 
blinded.
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.
17.9.
Study Completion/Termination
17.9.1.
Study Completion
The study is considered completed with the last visit for the last subject participating in either 
Stage 1 or Stage 2 of the study. The final data from the study site will be sent to the sponsor (or 

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designee) after completion of the final subject assessment at that study site, in the time frame 
specified in the Clinical Trial Agreement.
17.9.2.
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
study site is considered closed when all required documents and study supplies have been 
collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended 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 vaccine development
17.10. 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 and comparison with the CRFs. Subject 
privacy must, however, be respected. The investigator and study-site personnel are responsible 
for being present and available for consultation during routinely scheduled study-site audit visits 
conducted by the sponsor or its designees. 
Similar auditing procedures may also be conducted by agents of any regulatory body, either as 
part of a national GCP compliance program or to review the results of this study in support of a 
regulatory submission. The investigator should immediately notify the sponsor if he or she has
been contacted by a regulatory agency concerning an upcoming inspection.
17.11. 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 and may be apportioned between the consortium members, if contemplated and as 
detailed in the Consortium Agreement. 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.

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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 CRF data from all study sites that participated in the study. 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. 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. Further details regarding ownership and access rights by consortium 
members to the data and results of the study are detailed in the Consortium Agreement.
Consistent with Good Publication Practices and International Committee of Medical Journal 
Editors guidelines, the sponsor and consortium members shall have the right to publish such 
primary (multicenter) data and information as detailed in the Consortium Agreement without 
approval from the individual investigators. The individual investigators have the right to publish 
study site-specific data after the primary data are published. Further details regarding 
publications by consortium members and individual investigators are detailed in the Clinical 
Trial Agreement and Consortium Agreement. The relevant publication sections of the 
Consortium Agreement will be shared with the investigator once executed by all the consortium 
partners. For multicenter study designs and sub-study approaches, secondary results generally 
should not be published before the primary endpoints of a study have been published. Similarly, 
consortium members and 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 12 months of the 
availability of the final data (tables, listings, graphs), 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 Consortium Agreement and the 
Uniform Requirements for Manuscripts Submitted to Biomedical Journals, which state that the 
named authors must have made a significant contribution to the design of the study or analysis 
and interpretation of the data, provided critical review of the paper, and given final approval of 
the final version.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and/or disclose the existence of and the results of clinical studies as 
required by law.

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REFERENCES
1.
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.
2.
Centers for Disease Control and Prevention. Clinical Growth Chart. Available at: 
htttp://www.cdc.gov/growthcharts/clinical_charts.htm. Accessed 10 March 2015.
3.
Dosoo DK, Kayan K, Adu-Gyasi D et al. Haematological and biochemical reference values for healthy 
adults in the middle belt of Ghana. PLoS One. 2012;7(4):e36308. 
4.
Elizaga ML, Vasan S, Marovich MA, et al.; MVA Cardiac Safety Working Group. Prospective 
surveillance for cardiac adverse events in healthy adults receiving modified vaccinia Ankara vaccines: a 
systematic review. PLoS One. 2013;8(1):e54407.
5.
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.
6.
Friedrich B, Trefry J, Biggins J, et al. Potential vaccines and post-exposure treatments for filovirus 
infections. Viruses. 2012;4(9):1619-1650.
7.
IMVANEX suspension for injection. UK Summary of Product Characteristics. Available at: 
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Product_Information/human/002596/WC500147896.pdf. Accessed 9 October 2014.
8.
Investigator’s Brochure: JNJ-61210474 (Ad26.ZEBOV) Edition 3. Crucell Holland B.V. (Oct 2015). For 
updated information, refer to Edition 4 (Janssen Vaccines & Prevention, 23 June 2016).
9.
Investigator’s Brochure: MVA-BN-Filo (MVA-mBN226B) Edition 6. Bavarian Nordic A/S (Nov 2015).
For updated information, refer to Edition 10 (11 July 2016).
10.
Neff J, Modlin J, Birkhead GS, et al. Monitoring the safety of a smallpox vaccination program in the 
United States: report of the joint Smallpox Vaccine Safety Working Group of the advisory committee on 
immunization practices and the Armed Forces Epidemiological Board. Clin Infect Dis. 2008;46 
Suppl.3:S258-S270.
11.
Stittelaar KJ, Kuiken T, de Swart RL et al. Safety of Modified Vaccinia Virus Ankara (MVA) in immune-
suppressed macaques. Vaccine. 2001;19(27):3700-3709.
12.
Verheust C, Goossens M, Pauwels K, Breyer D. Biosafety aspects of Modified Vaccinia Virus Ankara 
(MVA)-based vectors used for gene therapy or vaccination. Vaccine. 2012 30;30(16):2623-2632.
13.
WHO Child Growth Standards (birth to 24 months). Available at: http://www.who.int/childgrowth/en. 
Accessed 10 March 2015.
14.
WHO Fact Sheet No103 Ebola Virus Disease 2014. Available at: 
http://www.who.int/mediacentre/factsheets/fs103/en/. Accessed 9 October 2014. 
15.
WHO Global Health Observatory data – meningitis 2010. Available at: 
http://www.who.int/gho/epidemic_diseases/meningitis/suspected_cases_deaths_text/en/. Accessed 
27 February 2017.
16.
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 27 February 2017

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ATTACHMENTS
Attachment 1:
Schematic Presentation of the IDMC Schedule for the Prime and Boost Vaccination 
The IDMC schedule applies to both the prime and the boost vaccination.

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Attachment 3:
Fever Management Algorithm

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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 vaccine, the conduct of the study, and the obligations of confidentiality.
Coordinating Investigator (where required):
Name (typed or printed):
Institution and Address:
Signature:
Date:
(Day Month Year)
Principal (Site) Investigator:
Name (typed or printed):
Institution and Address:
Telephone Number:
Signature:
Date:
(Day Month Year)
Sponsor's Responsible Medical Officer:
Name (typed or printed):
Cynthia Robinson, MD
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.
LAST PAGE

 
 
SIGNATURES 
 
 
 
 
Signed by  
Date  
 
Justification  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cynthia Robinson
03Oct2018, 11:15:52 AM, UTC
Document Approval