A Randomized, Observer-blind, Placebo-controlled, Phase 2 Study to Evaluate the Safety, Tolerability and Immunogenicity of Different Prime-boost Regimens of the Candidate Prophylactic Vaccines for Ebola Ad26.ZEBOV and MVA-BN-Filo in Healthy Adults, Including Elderly Subjects, HIV-infected Subjects, and Healthy Children in Two Age Strata in Africa
Phase: PHASE2
Conditions: Hemorrhagic Fever, Ebola
Sponsor: Janssen Vaccines & Prevention B.V.

Janssen Vaccines & Prevention B.V.*
Clinical Protocol
A Randomized, Observer-blind, Placebo-controlled, Phase 2 Study to Evaluate the Safety, 
Tolerability and Immunogenicity of Different Prime-boost Regimens of the Candidate 
Prophylactic Vaccines for Ebola Ad26.ZEBOV and MVA-BN-Filo in Healthy Adults, Including 
Elderly Subjects, HIV-infected Subjects, and Healthy Children in Two Age Strata in Africa
Protocol VAC52150EBL2002; Phase 2
AMENDMENT 3
Innovative Medicines Initiative-2
EBOVAC2 Consortium Partners
(London School of Hygiene and Tropical Medicine, 
Institut National de la Santé et de la Recherche Médicale, 
University of Oxford, Le Centre MURAZ and Janssen Vaccines & Prevention B.V.)
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.
Status:
Approved
Date:
4 May 2017
Prepared by:
Janssen Vaccines & Prevention B.V.
EDMS number:
EDMS-ERI-97109067, 12.0
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.
NCT02564523

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
2
Status: Approved, Date: 4 May 2017
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF ATTACHMENTS............................................................................................................................ 5
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 5
PROTOCOL AMENDMENTS....................................................................................................................... 6
SYNOPSIS.................................................................................................................................................. 20
TIME AND EVENTS SCHEDULE .............................................................................................................. 27
Cohort 1 (Groups 1-3) and Cohorts 2a and 2b (Groups 1-2)...................................................................... 27
Pediatric Cohort 3 (Groups 1-2).................................................................................................................. 31
ADDITIONAL TIME AND EVENTS SCHEDULE .......................................................................................34
Subjects Who Do Not Receive a Boost Vaccination Because of a Study Pause....................................... 34
COHORT 1 SUBSTUDY TIME AND EVENTS SCHEDULE...................................................................... 37
Subjects at Selected Sites Receiving a Third Vaccination (Cohort 1, Groups 1-2).................................... 37
ABBREVIATIONS ...................................................................................................................................... 39
DEFINITIONS OF TERMS..........................................................................................................................40
1.
INTRODUCTION................................................................................................................................41
1.1.
Background.................................................................................................................................... 41
Nonclinical Studies ..................................................................................................................... 42
1.1.1.
Clinical Studies ...........................................................................................................................43
1.1.2.
1.2.
Benefit/Risk Section.......................................................................................................................48
Known Benefits...........................................................................................................................48
1.2.1.
Potential Benefits........................................................................................................................48
1.2.2.
Known Risks...............................................................................................................................48
1.2.3.
Potential Risks............................................................................................................................48
1.2.4.
Overall Benefit/Risk Assessment ...............................................................................................50
1.2.5.
1.3.
Overall Rationale for the Study...................................................................................................... 51
2.
OBJECTIVES AND HYPOTHESIS ................................................................................................... 53
2.1.
Objectives ...................................................................................................................................... 53
2.2.
Hypothesis ..................................................................................................................................... 54
3.
STUDY DESIGN AND RATIONALE ................................................................................................. 54
3.1.
Overview of Study Design.............................................................................................................. 54
3.2.
Study Design Rationale.................................................................................................................. 59
4.
SUBJECT POPULATION.................................................................................................................. 61
4.1.
Inclusion Criteria ............................................................................................................................62
Inclusion Criteria for Healthy Adult and Elderly Subjects...........................................................62
4.1.1.
Additional Inclusion Criteria for HIV-infected Subjects...............................................................64
4.1.2.
Inclusion Criteria for Pediatric Subjects...................................................................................... 65
4.1.3.
4.2.
Exclusion Criteria ...........................................................................................................................67
Exclusion Criteria for Healthy Adult and Elderly Subjects..........................................................67
4.2.1.
Additional Exclusion Criteria for HIV-infected Subjects..............................................................69
4.2.2.
Exclusion Criteria for Pediatric Subjects..................................................................................... 69
4.2.3.
4.3.
Prohibitions and Restrictions ......................................................................................................... 71
5.
TREATMENT ALLOCATION AND BLINDING................................................................................. 72

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
3
Status: Approved, Date: 4 May 2017
6.
DOSAGE AND ADMINISTRATION .................................................................................................. 74
6.1.
General Instructions and Procedures ............................................................................................74
6.2.
Criteria for Postponement of Vaccination ...................................................................................... 76
6.3.
Contraindications to Boost and Third Vaccinations ....................................................................... 76
7.
TREATMENT COMPLIANCE............................................................................................................ 77
8.
PRESTUDY AND CONCOMITANT THERAPY ................................................................................ 77
9.
STUDY EVALUATIONS.................................................................................................................... 78
9.1.
Study Procedures...........................................................................................................................78
Overview..................................................................................................................................... 78
9.1.1.
Screening Phase ........................................................................................................................80
9.1.2.
Vaccination Phase (Prime and Boost)........................................................................................81
9.1.3.
Post-vaccination Phase .............................................................................................................. 82
9.1.4.
Long-term Follow-up................................................................................................................... 83
9.1.5.
Procedures in Case of a Study Pause........................................................................................83
9.1.6.
Cohort 1 Substudy (Third Vaccination).......................................................................................86
9.1.7.
VAC52150 Vaccine Development Roll-over Study .................................................................... 87
9.1.8.
9.2.
Endpoints ....................................................................................................................................... 87
9.3.
Safety Evaluations .........................................................................................................................88
Safety Assessments ................................................................................................................... 88
9.3.1.
Pausing Rules.............................................................................................................................92
9.3.2.
9.4.
Immunogenicity Evaluations .......................................................................................................... 93
9.5.
Vaccine-induced Seropositivity...................................................................................................... 95
9.6.
Sample Collection and Handling.................................................................................................... 95
10.
SUBJECT COMPLETION/DISCONTINUATION OF STUDY VACCINE/WITHDRAWAL 
FROM THE STUDY...........................................................................................................................95
10.1.
Completion..................................................................................................................................... 95
10.2.
Discontinuation of Study Vaccine/Withdrawal From the Study...................................................... 95
10.3.
Withdrawal From the Use of Research Samples........................................................................... 97
11.
STATISTICAL METHODS................................................................................................................. 97
11.1.
Endpoints ....................................................................................................................................... 98
Primary Endpoints ......................................................................................................................98
11.1.1.
Secondary Endpoint ................................................................................................................... 98
11.1.2.
Exploratory Endpoints................................................................................................................. 99
11.1.3.
11.2.
Sample Size Determination ........................................................................................................... 99
11.3.
Analysis Sets................................................................................................................................100
11.4.
Subject Information ......................................................................................................................101
11.5.
Safety Analyses ...........................................................................................................................101
11.6.
Immunogenicity Analyses ............................................................................................................ 102
11.7.
Interim Analyses...........................................................................................................................102
11.8.
Independent Data Monitoring Committee .................................................................................... 102
11.9.
Trial Management Team and Clinical Steering Committee.........................................................103
12.
ADVERSE EVENT REPORTING .................................................................................................... 103
12.1.
Definitions .................................................................................................................................... 103
Adverse Event Definitions and Classifications ......................................................................... 103
12.1.1.
Attribution Definitions................................................................................................................ 105
12.1.2.
Severity Criteria ........................................................................................................................106
12.1.3.
12.2.
Special Reporting Situations........................................................................................................ 106
12.3.
Procedures................................................................................................................................... 107
All Adverse Events.................................................................................................................... 107
12.3.1.
Serious Adverse Events ........................................................................................................... 108
12.3.2.
Immediate Reportable Events .................................................................................................. 109
12.3.3.
Pregnancy................................................................................................................................. 109
12.3.4.
12.4.
Contacting Sponsor Regarding Safety.........................................................................................110

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
4
Status: Approved, Date: 4 May 2017
13.
PRODUCT QUALITY COMPLAINT HANDLING............................................................................ 110
13.1.
Procedures................................................................................................................................... 110
13.2.
Contacting Sponsor Regarding Product Quality.......................................................................... 110
14.
STUDY VACCINE INFORMATION ................................................................................................. 111
14.1.
Description of Study Vaccines ..................................................................................................... 111
14.2.
Packaging and Labeling............................................................................................................... 111
14.3.
Preparation, Handling, and Storage.............................................................................................112
14.4.
Study Vaccine Accountability....................................................................................................... 112
15.
STUDY-SPECIFIC MATERIALS..................................................................................................... 113
16.
ETHICAL ASPECTS .......................................................................................................................113
16.1.
Study-specific Design Considerations .........................................................................................113
16.2.
Regulatory Ethics Compliance..................................................................................................... 114
Investigator Responsibilities..................................................................................................... 114
16.2.1.
Independent Ethics Committee or Institutional Review Board ................................................. 115
16.2.2.
Informed Consent and Assent Form.........................................................................................116
16.2.3.
Privacy of Personal Data .......................................................................................................... 117
16.2.4.
Long-term Retention of Samples for Additional Future Research............................................ 118
16.2.5.
Country Selection ..................................................................................................................... 118
16.2.6.
17.
ADMINISTRATIVE REQUIREMENTS ............................................................................................118
17.1.
Protocol Amendments.................................................................................................................. 118
17.2.
Regulatory Documentation .......................................................................................................... 119
Regulatory Approval/Notification ..............................................................................................119
17.2.1.
Required Prestudy Documentation...........................................................................................119
17.2.2.
17.3.
Subject Identification, Enrollment, and Screening Logs ..............................................................120
17.4.
Source Documentation................................................................................................................. 120
17.5.
Case Report Form Completion .................................................................................................... 121
17.6.
Data Quality Assurance/Quality Control ...................................................................................... 121
17.7.
Record Retention .........................................................................................................................121
17.8.
Monitoring .................................................................................................................................... 122
17.9.
Study Completion/Termination..................................................................................................... 123
Study Completion/End of Study................................................................................................... 123
17.9.1.
Study Termination........................................................................................................................123
17.9.2.
17.10.
On-site Audits...............................................................................................................................123
17.11.
Use of Information and Publication..............................................................................................124
REFERENCES.......................................................................................................................................... 126
ATTACHMENTS....................................................................................................................................... 128
INVESTIGATOR AGREEMENT ............................................................................................................... 139
LAST PAGE.............................................................................................................................................. 139

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
5
Status: Approved, Date: 4 May 2017
LIST OF ATTACHMENTS
Attachment 1: Test of Understanding (TOU) ............................................................................................ 128
Attachment 2: Toxicity Tables for Use in Trials Enrolling Healthy Adults................................................. 129
Attachment 3: Toxicity Tables for Use in Trials Enrolling Children Greater Than 3 Months of 
Age .................................................................................................................................... 134
Attachment 4: Hemoglobin Cut-off Values................................................................................................ 138
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Study Vaccination Schedules Groups 1-3........................................................................... 74
Table 2: 
Cohort 1 Substudy Vaccination Schedule (Groups 1-2, Selected Sites) ............................ 74
Table 3: 
Visit Windows ...................................................................................................................... 79
Table 4: 
Visit Windows for Subjects Who Elect to Receive a Late Boost Vaccination ..................... 84
Table 5: 
Visit Windows for Subjects Who are Not Willing or Not Allowed to Receive the 
Late Boost Vaccination........................................................................................................ 85
Table 6: 
Visit Windows ...................................................................................................................... 86
Table 7: 
Whole Blood Volumes for Immunogenicity Assessments................................................... 94
Table 8: 
Summary of Immunologic Assessments ............................................................................. 94
Table 9: 
Probability of Observing at Least One Adverse Event Given a True Adverse 
Event Incidence ................................................................................................................. 100
Table 10: 
Magnitude of Pairwise Difference to be Detected Between Vaccine Regimens 
for a Given Sample Size.................................................................................................... 100
FIGURES
Figure 1:
Schematic Overview of the Study ....................................................................................... 56

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
6
Status: Approved, Date: 4 May 2017
PROTOCOL AMENDMENTS
Protocol Version 
Issue Date
Original Protocol
30 March 2015
Amendment 1
26 June 2015
Amendment 2
9 September 2016
Amendment 3
4 May 2017
Amendments below are listed beginning with the most recent amendment.
Amendment_3 (this document)
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 1 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 1-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 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 1 year post prime at 
selected sites in approximately 90 healthy adults in Cohort 1 (Groups 1 and 2) in order to extend the findings to 
an African population and confirm the immunogenicity profile from the Phase 1 study.
This amendment also proposes to eliminate Cohort 4 (aged 1-3 years, inclusive) entirely in this protocol. Safety 
and immunogenicity data for this age group will be collected in 2 other studies within the program (Phase 2 and 
Phase 3 studies with approximately 1,400 and 976 children aged ≥1 year, respectively) reducing the need to 
collect these data within this study and allowing it to focus on healthy adult and elderly subjects, HIV-infected 
subjects and healthy children aged 4-17 years (all ages inclusive). The sponsor also proposes to remove the 
following immunogenicity assessments: pre-boost PBMC isolation in children from Cohort 3 and the 7-day post-
boost immunogenicity assessments in children from Cohorts 2b and 3.
Furthermore, the enrollment of subjects from VAC52150EBL2002 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 placebo) 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 
placebo), unless local regulations have additional requirements for follow-up. 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 
(SAEs) 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 to have 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. 
The changes made to the clinical protocol VAC52150EBL2002 Amendment 2 (dated 9 September 2016) are 
listed below, including the rationale of each change and a list of all applicable sections.
Rationale: A third vaccination with Ad26.ZEBOV or placebo will be administered to approximately 90 healthy 
adults in Cohort 1 (Groups 1 and 2) at selected sites at least 1 year post prime in order to confirm and extend the 
findings from a Phase 1 study. Information was added to clarify the procedures that need to be followed for these 
subjects.
SYNOPSIS

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
7
Status: Approved, Date: 4 May 2017
Time and Events Schedule
Cohort 1 Substudy Time and Events Schedule
1.2.4 Potential Risks
1.2.5 Overall Benefit/Risk Assessment
1.3 Overall Rationale for the Study
2.1 Objectives
3 STUDY DESIGN AND RATIONALE
4.2.1 Exclusion Criteria for Healthy Adult and Elderly Subjects
4.3 Prohibitions and Restrictions
5 TREATMENT ALLOCATION AND BLINDING
6 DOSAGE AND ADMINISTRATION
6.1 General Instructions and Procedures
6.2 Criteria for Postponement of Vaccination
6.3 Contraindications to Boost and Third Vaccination
8 PRESTUDY AND CONCOMITANT THERAPY
9.1 Study Procedures
9.1.5 Long-term Follow-up
9.1.7 Cohort 1 Substudy (Third Vaccination)
9.3.1 Safety Assessments
9.3.2 Pausing Rules
9.4 Immunogenicity Evaluations
10.1 Completion
11 STATISTICAL METHODS
11.1 Endpoints
11.3 Analysis Sets
11.5 Safety Analyses
11.6 Immunogenicity Analyses
11.7 Interim Analyses
12.3.1 All Adverse Events
Rationale: Cohort 4 (aged 1-3 years, inclusive) was eliminated. Safety and immunogenicity data for this age 
group will be collected in 2 other studies within the program (Phase 2 and Phase 3 studies with approximately 
1,400 and 976 children aged ≥1 year, respectively), reducing the need to collect these data within this study and 
allowing it to focus on healthy adult and elderly subjects, HIV-infected subjects and healthy children aged 
4-17 years (all ages inclusive). Consequently, the sample size was updated.
SYNOPSIS
Time and Events Schedule
1.3 Overall Rationale for the Study
2.1 Objectives
3.1 Overview of Study Design
4.1.3 Inclusion Criteria for Pediatric Subjects
4.2.3 Exclusion Criteria for Pediatric Subjects
5 TREATMENT ALLOCATION AND BLINDING
6 DOSAGE AND ADMINISTRATION
9.1.1 Overview
9.1.2 Screening Phase

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
8
Status: Approved, Date: 4 May 2017
9.1.3 Vaccination Phase (Prime and Boost)
9.3 Safety Evaluations
9.4 Immunogenicity Evaluations
11.2 Sample Size Determination
11.5 Safety Analyses
11.7 Interim Analyses
11.8 Independent Data Monitoring Committee
16.1 Study-specific Design Considerations
Rationale: The title of the study was updated to delete the third age stratum (Cohort 4) and to include the 
Cohort 1 substudy.
TITLE PAGE
SYNOPSIS
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 SAEs 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 to have 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 was 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 placebo) 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 placebo), unless local 
regulations have additional requirements for follow-up. Following these children for a total of 5 years was a 
commitment made to the relevant health authorities.
SYNOPSIS
3.1 Overview of Study Design
9.1.8 VAC52150 Vaccine Development 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 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. Secondary safety 
objectives/endpoints and exploratory immunology objectives/endpoints with regard to the substudy were added.
SYNOPSIS
2.1 Objectives
11.1.2 Secondary Endpoint
11.1.3 Exploratory Endpoints

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
9
Status: Approved, Date: 4 May 2017
Rationale: As there is no analysis planned for the peripheral blood mononuclear cell (PBMC) sample taken on 
the day of the boost vaccination in children from Cohort 3 and for the immunogenicity sample taken on the 7-day 
post-boost visit in children from Cohorts 2b and 3, these samples were removed.
Time and Events Schedule
9.1.1 Overview
9.4 Immunogenicity Evaluations
16.1 Study-specific Design Considerations
Rationale: Exclusion criterion 29 was updated to specify that pediatric subjects with weight-per-height below 
10th percentile according to Centers for Disease Control and Prevention growth charts should be excluded.
4.2.3 Exclusion Criteria for Pediatric Subjects
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 most severe abnormalities and toxicity gradings.
SYNOPSIS
11.5 Safety Analyses
Rationale: Inclusion criterion 15 for HIV-infected subjects was updated to add the use of viral load assessments 
to establish effectiveness of viral suppression, as the HIV-infected subjects must be on a stable regimen of Highly 
Active Antiretroviral Therapy whose purpose is to reduce viral load to undetectable levels.
4.1.2 Additional Inclusion Criteria for HIV-infected Subjects
Rationale: Minor textual changes have been made, in addition to updates to be in line with other current 
protocols.
SYNOPSIS
Time and Events Schedule
Additional Time and Events Schedule
Definitions of Terms
3.1 Overview of Study Design
4 SUBJECT POPULATION
4.2.1 Exclusion Criteria for Healthy Adult and Elderly Subjects
5 TREATMENT ALLOCATION AND BLINDING
9.1.1 Overview
9.1.3 Vaccination Phase (Prime and Boost)
9.1.5 Long-term Follow-up
9.3.1 Safety Assessments
10.2 Discontinuation of Study Vaccine/Withdrawal From the Study
12.3.4 Pregnancy
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 VAC52150EBL2002 Amendment 3
10
Status: Approved, Date: 4 May 2017
Amendment_2 (9 September 2016)
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of Directive 
2001/20/EC of the European Parliament and the Council of the European Union.  
The overall reason for the amendment: This amendment includes the request of the Center for Biologics 
Evaluation and Research (CBER, a division of United States [US] Food and Drug Administration [FDA]) to 
change the age ranges of Cohorts 3 and 4 and to extend the safety follow-up to 6 months post-boost. The latter
request was originally made for other VAC52150 protocols and has now also been implemented for this protocol.
The sponsor halted vaccinations following a case of Miller Fisher syndrome after receipt of MVA-BN-Filo or 
placebo in a clinical study. This interruption continued until a revised informed consent form (ICF) containing 
updated safety language for the current study VAC52150EBL2002 was prepared and approval to restart the study 
was granted by the relevant competent authority. 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. Based on the request of the Agence Nationale de Sécurité du Médicament et des 
produits de santé (ANSM) for study VAC52150EBL2001, 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 VAC52150EBL2002 Amendment 1 (dated 26 June 2015) are listed 
below, including the rationale of each change and a list of all applicable sections.
Rationale: As requested by the CBER (US FDA), the age ranges of Cohort 3 and Cohort 4 have been changed to 
4 to 11 years (Cohort 3) and 1 to 3 years (Cohort 4) to align with World Health Organization (WHO)-defined age 
cohorts which effectively increases the number of subjects aged 1 to 3 years. Since this age group has a different 
immune response to vaccination than older children and adults, the increased sample size of Cohort 4 will 
provide deeper understanding of the immunogenicity of the vaccine.
SYNOPSIS
Time and Events Schedule
3.1 Overview of Study Design
4.1.3 Inclusion Criteria for Pediatric Subjects
6 DOSAGE AND ADMINISTRATION
9.3.1 Safety Assessments
9.4 Immunogenicity Evaluations
Rationale: As requested by the CBER (US FDA), the 6-month post-prime visit has been changed to 6-month 
post-boost visit (6-month post-prime visit will be retained for subjects who are outside the protocol-defined boost 
vaccination window and elect not to receive a late boost vaccination). In addition, a statement has been added that 
subjects who complete the 6-month post-prime visit (which has been replaced with the 6-month post-boost visit 
per the current protocol amendment) prior to approval of Amendment 2 will be required to also attend the 
6-month post-boost visit after approval of Amendment 2.
SYNOPSIS
Time and Events Schedule
1.2.4 Potential Risks
3.1 Overview of Study Design
4.3 Prohibitions and Restrictions
5 TREATMENT ALLOCATION AND BLINDING
9.1.1 Overview
9.1.4 Post-vaccination Phase
9.1.5 Long-term Follow-up
11.6 Immunogenicity Analyses

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
11
Status: Approved, Date: 4 May 2017
Rationale: Information was added to clarify the procedures that need to be followed for subjects who are affected 
by a study pause. A separate Time and Events Schedule was created for subjects who were primed prior to a
pause and do not/will not receive a boost vaccination because of a study pause. Because there will be subjects 
who do not receive a boost vaccination, some post-boost vaccination visits have been changed to post-last 
vaccination visits (eg, for collection of adverse events).
SYNOPSIS
Additional Time and Events Schedule
1.2.4 Potential Risks
3 STUDY DESIGN AND RATIONALE
4.2.1 Exclusion Criteria for Healthy Adult and Elderly Subjects
4.3 Prohibitions and Restrictions
9.1 Study Procedures
9.1.6 Procedures in Case of a Study Pause
9.3.1 Safety Assessments
10.1 Completion
11 STATISTICAL METHODS
12.3.1 All Adverse Events
Rationale: As requested by the CBER (US FDA), the safety laboratory assessments at screening are to be 
performed within 28 days prior to the prime vaccination and may be repeated if they fall outside this time 
window. Screening safety laboratory assessments can also be done on Day 1 before vaccination and subjects may 
be randomized on the same day when they satisfy all selection criteria; for example, if a woman returns for a 
repeat urinalysis due to menses, she may be randomized on that same day provided all selection criteria are met
and results are known prior to randomization. If rescreening is required, all screening procedures (except TOU) 
should be repeated. As a result of the pause, subjects whose screening period was longer than the protocol-
defined 8 weeks will be allowed to rescreen once, but must have new safety laboratory assessments (including 
HIV, follicle stimulating hormone [FSH] [if applicable], electrocardiogram [ECG], hematology, biochemistry, 
urinalysis, vital signs and physical examination) within 28 days of the prime vaccination. The TOU does not need 
to be repeated.
Time and Events Schedule
4.1.1 Inclusion Criteria for Healthy Adult and Elderly Subjects
4.1.3 Inclusion Criteria for Pediatric Subjects
9.1.2 Screening Phase
Rationale: A change in approximate whole blood volumes in Cohorts 3 and 4 is necessitated by a number of 
factors: (i) each site requires more than the previously allotted volumes to perform hematology and serum 
chemistry tests and each site requires slightly different volumes (hence, the blood volumes for safety endpoints 
have been deleted from the Time and Events Schedule); (ii) immunogenicity assays require a minimum blood 
volume to provide a sufficient sample for analysis; reducing the volumes any further jeopardizes the secondary 
endpoint in the study; (iii) there are technical issues with reducing the blood volumes with availability of 
appropriate phlebotomy tubes and additional problems associated with dividing a single sample into multiple 
aliquots in a sterile manner. The minimum whole blood volume that satisfies both the safety and immunogenicity 
endpoints will be taken.
Time and Events Schedule
9.1.1 Overview
9.3.1 Safety Assessments
9.4 Immunogenicity Evaluations
16.1 Study-specific Design Considerations

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
12
Status: Approved, Date: 4 May 2017
Rationale: The time of unblinding of sponsor personnel for regulatory submission has been changed to when the 
last subject in a cohort has completed the 6-month post-boost visit or discontinued earlier. All subjects within a 
cohort will be followed in a blinded manner by the site until the last subject in that cohort has completed the 
study. Any subject who completes either the 6-month post-prime and/or the Day 365 visit prior to approval of 
Amendment 2 will be required to attend the 6-month post-boost and the Day 365 visit after approval of 
Amendment 2. A subject will be considered to have completed the study if he or she has completed all 
assessments at the 6-month post-boost vaccination visit or at the Day 365 visit, whichever occurs later.
SYNOPSIS
Time and Events Schedule
1.2.4 Potential Risks
3.1 Overview of Study Design
5 TREATMENT ALLOCATION AND BLINDING
9.1.5 Long-term Follow-up
10.1 Completion
11.7 Interim Analyses
Rationale: The primary analysis has been changed to when all subjects in Cohort 1 have completed the 6-month
post-boost visit or discontinued earlier.
SYNOPSIS
3.1 Overview of Study Design
11 STATISTICAL METHODS
Rationale: The interim analysis on safety and selected immunogenicity data in each cohort has been changed to 
when all subjects have completed the 6-month post-boost visit. Additional interim analyses during the study for 
the purpose of informing future vaccine-related decisions in a timely manner, were deleted.
SYNOPSIS
3.1 Overview of Study Design
5 TREATMENT ALLOCATION AND BLINDING
11.7 Interim Analyses

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
13
Status: Approved, Date: 4 May 2017
Rationale: As requested by the ANSM, wording on the collection of “Immediate Reportable Events” was added 
after one subject in 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.
SYNOPSIS
Time and Events Schedule
1.2.5 Overall Benefit/Risk Assessment
3.1 Overview of Study Design
8 PRESTUDY AND CONCOMITANT THERAPY
9.1.3 Vaccination Phase (Prime and Boost)
9.1.4 Post-vaccination Phase
9.1.5 Long-term Follow-up
9.1.6 Procedures in Case of a Study Pause
9.3.1 Safety Assessments
11.1.1 Primary Endpoints
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: Adverse events of special interest (cardiovascular events) will no longer be collected as no 
cardiovascular events have been associated with the current MVA-BN-Filo vaccine. Information was added on 
the procedure that needs to be followed in case any cardiac sign or symptom develops after the boost vaccination. 
1.2.5 Overall Benefit/Risk Assessment
9.3.1 Safety Assessments
12.2 Special Reporting Situations
12.3.1 All Adverse Events
Rationale: The statement that a male subject’s study vaccine should be permanently discontinued if his partner 
becomes pregnant, has been removed. The current biodistribution and reprotoxicity data support the 
recommendation that there is a negligible risk to the partner of a male vaccinated subject if she becomes 
pregnant.
10.2 Discontinuation of Study Vaccine
Rationale: The inclusion criteria have been modified to specify that subjects with hemoglobin lower than the 
institutional normal reference range should not be included in the study.
4.1.1 Inclusion Criteria for Healthy Adult and Elderly Subjects
4.1.3 Inclusion Criteria for Pediatric Subjects
Rationale: Criteria regarding contraceptive requirements have been clarified. In addition, the statement that the 
birth control method used by the female partner of a male subject should be documented, has been removed. The 
current biodistribution data suggest that there is no vaccine present in tissues other than the inoculated muscle and 
regional lymph nodes. Therefore, the risk to the partner of a male participant is negligible and it is unnecessary to 
confirm additional contraceptive use by the partner. Consistent condom use in the male participant will continue 
to be emphasized.
4.1.1 Inclusion Criteria for Healthy Adult and Elderly Subjects
4.1.3 Inclusion Criteria for Pediatric Subjects
4.3 Prohibitions and Restrictions

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
14
Status: Approved, Date: 4 May 2017
Rationale: One case of chest pain, that might be indicative of pericarditis and that was not finally confirmed, was 
observed in the MVA-BN clinical trial program and has been added to the Potential Risks section.
1.2.4 Potential Risks
Rationale: The analysis of response patterns over time for the immunologic parameters was deleted, since this 
analysis will not be performed.
SYNOPSIS
11.6 Immunogenicity Analyses
Rationale: Information regarding the marketing authorization of MVA-BN and the Phase 3 clinical study 
POX-MVA-013 has been updated. 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
REFERENCES
Rationale: The VAC52150 Vaccine Development Registry was replaced by a roll-over study. The statement 
‘(non-participating) partners of male subjects who become pregnant during the study and up to 3 months after the 
prime vaccination or up to 1 month after the boost vaccination (whichever is longer) will be approached to 
consent for enrollment of their children into the registry’ (added per Amendment 1) has been removed, since 
these children will no longer be followed. Further details regarding enrollment have been added, such as the 
inclusion of placebo subjects before unblinding of the current study.
SYNOPSIS
3.1 Overview of Study Design
9.1.8 VAC52150 Vaccine Development Roll-over Study
12.3.4 Pregnancy
Rationale: Immunogenicity objectives, endpoints and assessments have been revised and corrected. All 
secondary immunogenicity objectives and endpoints were shifted to exploratory objectives and endpoints, except 
for immune responses measured by ELISA.
SYNOPSIS
2.1 Objectives
9.4 Immunogenicity Evaluations
11.1.2 Secondary Endpoint
11.1.3 Exploratory Endpoints
Rationale: Information on remote audits was added.
17.10 On-site Audits
Rationale: The name of the sponsor changed from Crucell Holland B.V. to Janssen Vaccines & Prevention B.V. 
(formerly known as Crucell Holland B.V.).
TITLE PAGE
1 INTRODUCTION
14.1 Description of Study Vaccines
INVESTIGATOR AGREEMENT

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
15
Status: Approved, Date: 4 May 2017
Rationale: The protocol has been updated to be in line with the current protocol template (version 6 June 2016).
4 SUBJECT POPULATION
9.1.3 Vaccination Phase (Prime and Boost)
9.1.4 Post-vaccination Phase
9.3.1 Safety Assessments
10 SUBJECT COMPLETION/DISCONTINUATION OF STUDY VACCINE/WITHDRAWAL FROM THE 
STUDY
12.1.1 Adverse Event Definitions and Classifications
12.2 Special Reporting Situations
12.3.1 All Adverse Events
12.3.4 Pregnancy
12.4 Contacting Sponsor Regarding Safety
13.2 Contacting Sponsor Regarding Product Quality
16.1 Study-specific Design Considerations
16.2.2 Independent Ethics Committee or Institutional Review Board
16.2.3 Informed Consent and Assent Form
16.2.5 Long-term Retention of Samples for Additional Future Research
16.2.6 Country Selection
17.1 Protocol Amendments
17.4 Source Documentation
17.5 Case Report Form Completion
17.6 Data Quality Assurance/Quality Control
17.7 Record Retention
17.8 Monitoring
17.9.1 Study Completion/End of Study
17.10 On-site Audits
17.11 Use of Information and Publication

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
16
Status: Approved, Date: 4 May 2017
Rationale: Minor textual changes have been made, in addition to modifications for clarity and updates to be in 
line with other current protocols.
SYNOPSIS
Time and Events Schedule
ABBREVIATIONS
Definitions of Terms
1 INTRODUCTION
3 STUDY DESIGN AND RATIONALE
4.1.1 Inclusion Criteria for Healthy Adult and Elderly Subjects
4.1.3 Inclusion Criteria for Pediatric Subjects
4.2.3 Exclusion Criteria for Pediatric Subjects
5 TREATMENT ALLOCATION AND BLINDING
6.1 General Instructions and Procedures
6.3 Contraindications to Boost Vaccination
9.1.1 Overview
9.1.2 Screening Phase
9.1.5 Long-term Follow-up
9.3 Safety Evaluations
9.4 Immunogenicity Evaluations
10.1 Completion
10.2 Discontinuation of Study Vaccine/Withdrawal From the Study
11.2 Sample Size Determination
11.3 Analysis Sets
12.1.1 Adverse Event Definitions and Classifications
17.10 On-site Audits
ATTACHMENTS

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
17
Status: Approved, Date: 4 May 2017
Amendment_1 (26 June 2015)
The overall reason for the amendment: This amendment was written in response to the Assisted Review of the 
Janssen Ebola Zaire Vaccine Clinical Trials Application meeting of 9-11 June 2015. A few additional changes 
(not triggered by the meeting) have been implemented. Further, modifications were made throughout the protocol 
to correct minor errors, inconsistencies and/or for clarity.
The table below gives an overview of the rationale for each change and all applicable sections. 
The following changes were made following the meeting:
Rationale: The 84-day prime-boost interval has been dropped in Cohorts 2 to 4. The sample size of the dropped 
regimen in Cohort 2 to 4 has been redistributed to the 28- and 56-day prime-boost intervals in Cohort 1 to 
increase the number of adult or elderly subjects. Consequently, the primary analysis will be performed when all 
subjects in Groups 1 and 2 in Cohort 1 have completed the 42-day post-boost visit or discontinued earlier.
SYNOPSIS
Time and Events Schedule
2.1 Objectives
3.1 Overview of Study Design
3.2 Study Design Rationale
5 TREATMENT ALLOCATION AND BLINDING
6 DOSAGE AND ADMINISTRATION
11 STATISTICAL METHODS
11.2 Sample Size Determination
11.7 Interim Analyses
Rationale: Further text has been added to clarify the process for progression to the next cohort, and a change has 
been implemented for Cohort 4. An interim analysis will be performed after the first 36 subjects in Cohort 3 have 
completed their 21-day post-boost visit on all available safety and immunogenicity data collected to this point in 
the study, for the purpose of enrolling Cohort 4.
SYNOPSIS
3.1 Overview of Study Design
11.7 Interim Analyses
11.8 Independent Data Monitoring Committee
Rationale: Also partners of male subjects who become pregnant during the study and up to 3 months after the 
prime vaccination or up to 1 month after the boost vaccination (whichever is longer) will be approached to 
consent for enrollment of their children into the registry. These children will be followed for a total period of 
5 years.
9.1.8 VAC52150 Vaccine Development 
12.3.4 Pregnancy
Rationale: The wording ‘health care worker’ has been replaced with language appropriate for the different sites: 
‘For illiterate subjects or those having difficulty completing the diary independently, the sites will make 
arrangements to have the diary completed according to their local practice’.
SYNOPSIS
Time and Events Schedule
1.2.5 Overall Benefit/Risk Assessment
3.1 Overview of Study Design
9.1.3 Vaccination Phase (Prime and Boost)

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
18
Status: Approved, Date: 4 May 2017
Rationale: Follow-up of CD4+ cell count in the HIV-infected cohort will be part of the clinical laboratory 
assessments with sampling at screening, on Day 1, on the day of boost vaccination and at 42 days after the boost 
vaccination. 
Time and Events Schedule
9.3.1 Safety Assessments
Rationale: The test of understanding (TOU) will be administered after reading, but before signing, the informed 
consent form (ICF)/assent.
Time and Events Schedule
9.1.2 Screening Phase
16.1 Study-specific Design Considerations
Rationale: Further clarification on the approximate blood volumes collected for the different study procedures at 
each scheduled visit and the cumulative blood draws have been added.
Time and Events Schedule
9.1.1 Overview
16.1 Study-specific Design Considerations
Rationale: The inclusion criteria have been modified to specify that subjects with hemoglobin outside the local 
laboratory’s reference range should not be included in the study. Appropriate hemoglobin cut-off values for all 
subjects have been added in case reference ranges for the local laboratories do not exist.
4.1.1 Inclusion Criteria for Healthy Adult and Elderly Subjects
4.1.3 Inclusion Criteria for Pediatric Subjects
ATTACHMENTS
Rationale: Clarification is added that subjects with malignancies who are currently being treated or are not 
surgical cures are excluded to ensure that a subject’s health status is adequate.
4.2.1 Exclusion Criteria for Healthy Adult and Elderly Subjects
Rationale: Text concerning the investigator’s responsibility to ensure adequate counseling and follow-up will be 
made available if the HIV or pregnancy test is positive in order to maintain subject confidentiality has been 
added.
4.1.1 Inclusion Criteria for Healthy Adult and Elderly Subjects
4.2.1 Exclusion Criteria for Healthy Adult and Elderly Subjects
4.1.3 Inclusion Criteria for Pediatric Subjects
4.2.3 Exclusion Criteria for Pediatric Subjects
Rationale: The language on the monitoring of subjects following each vaccination has been clarified. In addition, 
text concerning the investigator’s responsibility to provide emergency medical care during the post-vaccination 
observation period and to make arrangements for ongoing care has been added.
SYNOPSIS
1.2.5 Overall Benefit/Risk Assessment
3.1 Overview of Study Design
6.1 General Instructions and Procedures
9.3.1 Safety Assessments

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
19
Status: Approved, Date: 4 May 2017
Rationale: Any safety reports/interim data reviewed by the IDMC and the recommendations of the IDMC will be 
shared with the local health authorities and the IECs/IRBs.
11.8 Independent Data Monitoring Committee
Rationale: The statement that ‘the results from Ebola virus serological screening tests should be interpreted with 
caution as the subject could have a false positive test (not truly infected with Ebola virus) as a result of an 
immune response to the candidate Ebola vaccine’ has been specified on the ‘wallet (study) card’.
12.3.1 All Adverse Events
Rationale: The sponsor will establish a Material Transfer Agreement between all relevant parties taking into 
account national regulations.
16.2.5 Long-term Retention of Samples for Additional Future Research
The following additional changes were made: 
Rationale: The diary should be completed at approximately the same time each day.
SYNOPSIS
Time and Events Schedule
1.2.5 Overall Benefit/Risk Assessment
3.1 Overview of Study Design
9.1.3 Vaccination Phase (Prime and Boost)
9.3.1 Safety Assessments
12.3.1 All Adverse Events
Rationale: An absolute number (instead of a proportion) for subjects contributing to the PBMC samples has been 
provided. 
SYNOPSIS
Time and Events Schedule
3.1 Overview of Study Design
9.4 Immunogenicity Evaluations
Rationale: All urinalyses should be collected as freshly voided, mid-stream, clean catch samples obtained after 
proper cleansing.
4.1.1 Inclusion Criteria for Healthy Adult and Elderly Subjects
4.1.3 Inclusion Criteria for Pediatric Subjects
Rationale: Any vaccines received during the study should be recorded.
8 PRESTUDY AND CONCOMITANT THERAPY
Rationale: Modifications to correct minor errors, inconsistencies and/or for clarity throughout the document. The
selection criteria have been reorganized in order to group all inclusion and all exclusion criteria.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
20
Status: Approved, Date: 4 May 2017
SYNOPSIS
A Randomized, Observer-blind, Placebo-controlled, Phase 2 Study to Evaluate the Safety, Tolerability 
and Immunogenicity of Different Prime-boost Regimens of the Candidate Prophylactic Vaccines for 
Ebola Ad26.ZEBOV and MVA-BN-Filo in Healthy Adults, Including Elderly Subjects, HIV-infected 
Subjects, and Healthy Children in Two Age Strata in Africa
The sponsor, in collaboration with Bavarian Nordic (BN) and in conjunction with an Innovative 
Medicines Initiative (IMI) consortium led by the Institut National de la Santé et de la Recherche Médicale 
(INSERM), is investigating the potential of a prophylactic Ebola vaccine regimen comprised of the 
following 2 candidate Ebola vaccines:
Ad26.ZEBOV is a monovalent vaccine expressing the full length Ebola virus (EBOV, formerly known as 
Zaire ebolavirus) Mayinga glycoprotein (GP), and is produced in the human cell line PER.C6®.
MVA-mBN226B, further referred to as Modified Vaccinia Ankara (MVA)-BN-Filo®, is a multivalent 
vaccine expressing the Sudan virus (SUDV) GP, the EBOV GP, the Marburg virus (MARV) Musoke GP, 
and the Tai Forest virus (TAFV, formerly known as Côte d’Ivoire ebolavirus) nucleoprotein (NP), and is 
produced in chicken embryo fibroblast cells. The EBOV GP expressed by MVA-BN-Filo has 100% 
homology to the one expressed by Ad26.ZEBOV.
In this Phase 2 study, the sponsor’s adenovirus serotype 26 (Ad26) vector expressing the EBOV Mayinga 
GP (Ad26.ZEBOV) and the MVA-BN vector with EBOV, SUDV and MARV GP inserts and TAFV NP 
insert (MVA-BN-Filo) will be evaluated as a heterologous 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 28, 56 or 84 days later. In a substudy, 
Ad26.ZEBOV is also used as a third vaccination. The EBOV GP that is currently circulating in West 
Africa has 97% homology to the EBOV GP used in this vaccine regimen. 
OBJECTIVES AND HYPOTHESIS
Primary Objective
The primary objective is to assess the safety and tolerability of different vaccination schedules of 
Ad26.ZEBOV and MVA-BN-Filo administered intramuscularly (IM) as heterologous prime-boost 
regimens on Days 1 and 29, Days 1 and 57, or Days 1 and 85, in healthy adults, including elderly 
subjects, and on Days 1 and 29 and Days 1 and 57 in human immunodeficiency virus (HIV)-infected 
subjects and healthy children in 2 age strata.
Secondary Objectives
The secondary objectives are:

To assess humoral immune responses, as measured by enzyme-linked immunosorbent assay
(ELISA), to the EBOV GP at 21 days post boost of different vaccination schedules of Ad26.ZEBOV 
and MVA-BN-Filo administered IM as heterologous prime-boost regimens on Days 1 and 29, 
Days 1 and 57, or Days 1 and 85, in healthy adults, including elderly subjects, and on Days 1 and 29 
and Days 1 and 57 in HIV-infected subjects and healthy children in 2 age strata.

To assess the safety and tolerability of a third vaccination with Ad26.ZEBOV administered at least
1 year post prime in a subset of approximately 90 healthy adults, including elderly subjects, in 
Cohort 1 (Groups 1 and 2).

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
21
Status: Approved, Date: 4 May 2017
Exploratory Objectives
The exploratory objectives are:

To assess humoral immune responses, as measured by ELISA, to the EBOV GP at other relevant
time points of different vaccination schedules of Ad26.ZEBOV and MVA-BN-Filo administered IM 
as heterologous prime-boost regimens on Days 1 and 29, Days 1 and 57, or Days 1 and 85, in healthy 
adults, including elderly subjects, and on Days 1 and 29 and Days 1 and 57 in HIV-infected subjects 
and healthy children in 2 age strata.

To assess the neutralizing capacity of the EBOV GP-specific humoral immune responses, as 
measured by virus neutralization assay, to the EBOV GP of different vaccination schedules of 
Ad26.ZEBOV and MVA-BN-Filo administered IM as heterologous prime-boost regimens on Days 1 
and 29, Days 1 and 57, or Days 1 and 85, in healthy adults, including elderly subjects, and on Days 1 
and 29 and Days 1 and 57 in HIV infected subjects and healthy children in 2 age strata.

To explore humoral and cellular immune responses to different EBOV GPs and/or the adenovirus 
and/or MVA backbones of the various vaccination schedules tested. 

To explore humoral and cellular immune responses to filovirus GPs and/or TAFV NP, if assays are 
available.

To assess humoral immune responses, as measured by ELISA, to the EBOV GP at various time
points following a third vaccination with Ad26.ZEBOV at least 1 year post prime in approximately 
90 healthy adults, including elderly subjects, in Cohort 1 (Groups 1 and 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.
OVERVIEW OF STUDY DESIGN
This is a randomized, observer-blind, placebo-controlled, parallel-group, multicenter, Phase 2 study in 
Africa to evaluate the safety, tolerability and immunogenicity of different heterologous prime-boost 
regimens using Ad26.ZEBOV at a dose of 5x1010 viral particles (vp) as prime and MVA-BN-Filo at a 
dose of 1x108 infectious units (Inf U, nominal titer) as boost at a 28-, 56- or 84-day interval in healthy 
adult and elderly subjects. The same prime-boost schedules, except for the 84-day interval, will be 
evaluated in HIV-infected subjects and healthy children in 2 age strata. At selected sites in Cohort 1 
(Groups 1 and 2), a third vaccination with Ad26.ZEBOV will be administered at least 1 year post prime to 
subjects who consent to this (Cohort 1 substudy). Subjects who received a late boost vaccination or did 
not receive the boost vaccination at all due to a study pause will not be included in the Cohort 1 substudy.
This study will enroll a planned total number of 1,056 subjects, who have never received a candidate 
Ebola vaccine and have no prior exposure to Ebola virus (including travel to epidemic Ebola areas less 
than 1 month prior to screening) or a diagnosis of Ebola virus disease.
The study is comprised of 3 cohorts, which will be enrolled sequentially: healthy adult and elderly 
subjects (aged 18 years up to 70 years inclusive, Cohort 1), HIV-infected subjects (aged 18 to 50 years 
inclusive, Cohort 2a) and healthy children in 2 age strata (adolescents aged 12 to 17 years inclusive, 
Cohort 2b; children aged 4 to 11 years inclusive, Cohort 3). The prime-boost regimens that will be 
evaluated in this study will differ only in the timing of the boost vaccination (ie, 28, 56 or 84 days after 
prime, respectively referred to as Groups 1, 2 and 3), while the dose of each study vaccine 
(Ad26.ZEBOV, MVA-BN-Filo or placebo) and the sequence of prime-boost vaccination will be identical. 
Groups 1 and 2 will be evaluated in each cohort, while Group 3 (84-day interval) will be evaluated in 
Cohort 1 only. 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
22
Status: Approved, Date: 4 May 2017
In Cohort 1, subjects will be enrolled in parallel and randomized in a 1:1:1 ratio to Groups 1, 2 and 3 at 
baseline until a target of 132 subjects have been included in Group 3. Afterwards, randomization in this 
cohort will proceed in a 1:1 ratio to Groups 1 and 2. In Cohorts 2a, 2b, and 3, subjects will be enrolled in 
parallel and randomized in a 1:1 ratio to Groups 1 and 2 at baseline. Within each group (for all cohorts), 
subjects will be randomized in a 5:1 ratio to receive Ad26.ZEBOV and MVA-BN-Filo versus placebo.
Available interim analysis results of 7-day post-prime safety and immunogenicity data from the ongoing 
and/or planned Phase 1 studies (studies in Europe, United States [US] and Africa) will be provided before 
the start of the present study, which will start with Cohort 1. Progression to the next cohort will proceed 
following favorable Independent Data Monitoring Committee (IDMC) review:

Cohorts 2a and 2b can start when 25% of subjects in Cohort 1 have completed their 7-day post-
prime visit.

Cohort 3 can start when 50% of subjects in Cohort 2b have completed their 7-day post-prime 
visit.
The real-time monitoring of blinded data will be conducted by the sponsor. The interim data (unblinded) 
will be provided to and reviewed by the IDMC. The decision to open Cohorts 2a, 2b, and 3 will be based 
on the sponsor’s and the IDMC’s review of the interim safety data. Progression to the next cohort will 
also take into account pre-specified pausing rules. 
For each cohort, unblinding of sponsor personnel to study vaccine allocation will occur after the last 
subject in that cohort has completed the 6-month post-boost visit or discontinued earlier. All subjects 
within a cohort will be followed in a blinded manner by the site until the last subject in that cohort has 
completed the study. A subject will be considered to have completed the study if he or she has completed 
all assessments at the 6-month post-boost vaccination visit or at the Day 365 visit (1-year post third 
vaccination visit for Cohort 1 substudy), whichever occurs later.
All subjects will receive the study vaccine through IM injection in the deltoid muscle, either 
Ad26.ZEBOV (5x1010 vp) on Day 1, followed by a boost vaccination of MVA-BN-Filo (1x108 Inf U, 
nominal titer) on Day 29, 57 or 85; or placebo (0.9% saline) on Day 1, followed by a boost vaccination of 
placebo (0.9% saline) on Day 29, 57 or 85. 
In a substudy at selected sites, approximately 90 healthy adult subjects in Cohort 1 (Groups 1 and 2) will 
receive a third vaccination with Ad26.ZEBOV at 5x1010 vp or placebo at least 1 year post prime 
vaccination. Subjects who received Ad26.ZEBOV and MVA-BN-Filo will receive Ad26.ZEBOV as third 
vaccination. Subjects who received placebo will receive placebo as third vaccination.
The study consists of a screening phase of up to 8 weeks (starting from the moment the subject signs the 
informed consent form [ICF] and/or assent), a vaccination phase in which subjects will be vaccinated at 
baseline (Day 1) followed by a boost vaccination on Day 29, 57 or 85, a post-vaccination phase and 
long-term follow-up phase until Day 365. The Cohort 1 substudy consists of a vaccination phase in which 
subjects will be vaccinated at least 1 year post prime vaccination, a post-vaccination phase, and a long-
term follow-up phase until the 1-year post third vaccination visit. All subjects within a cohort will be 
followed in a blinded manner by the site until the last subject in that cohort has completed the study. Any
subject who completed either the 6-month post-prime and/or the Day 365 visit prior to approval of 
Amendment 2 was required to attend the 6-month post-boost and the Day 365 visit after approval of 
Amendment 2.
While Cohort 1 was enrolling, the sponsor halted all vaccinations in this study due to the occurrence of a 
serious and very rare condition, Miller Fisher syndrome, reported in study VAC52150EBL2001, until a 
revised ICF was prepared and approval to restart the study was granted by the relevant competent 
authority. This interruption in dosing affected over 200 consented subjects, some who were awaiting 
prime vaccination and some awaiting boost vaccination. When approval was granted to restart the study 
under Amendment 1, a late boost vaccination has been offered to those subjects who were out-of-window 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
23
Status: Approved, Date: 4 May 2017
for the boost vaccination, unless it was prohibited. Those subjects who agreed to the late boost have been 
following the procedures as outlined in Amendment 1. 
All subjects (including placebo) who were primed prior to the pause and did not/will not receive a late 
boost vaccination are being followed every 3 months after the prime vaccination for safety until Day 365
(see Additional Time and Events Schedule for subjects who do not receive a boost vaccination because of 
a study pause). Therefore, non-serious adverse events will be reported until the 42-day post-last 
vaccination (excluding third vaccination) visit rather than the 42-day post-boost vaccination visit. Serious 
adverse events and immediate reportable events (IREs) will be reported throughout the study until 
Day 365. 
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 placebo) 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 placebo) (unless local regulations have additional requirements for follow-up) will be
eligible for enrollment into the VAC52150 Vaccine Development Roll-over study (VAC52150EBL4001)
for long-term surveillance (for a total of up to 60 months after the prime vaccination). After unblinding, 
only female subjects and the children of female subjects who received Ad26.ZEBOV and/or MVA-BN-
Filo will remain in the VAC52150 Vaccine Development Roll-over study for long-term surveillance. After 
unblinding, female subjects and the children of female subjects who received placebo and have already 
been enrolled into the VAC52150 Vaccine Development Roll-over study will be discontinued from 
further participation in the roll-over study.
SUBJECT POPULATION
Screening of subjects for eligibility will be performed within 8 weeks before administration of study 
vaccine on Day 1. The study population will consist of a planned total number of 1,056 subjects, 
including healthy adult and elderly subjects (aged 18 to 70 years inclusive, Cohort 1), HIV-infected 
subjects (aged 18 to 50 years inclusive, Cohort 2a), and healthy children in 2 age strata (adolescents aged 
12 to 17 years inclusive, Cohort 2b; children aged 4 to 11 years inclusive, Cohort 3) in Africa.
DOSAGE AND ADMINISTRATION
Study vaccines (Ad26.ZEBOV, MVA-BN-Filo or placebo) will be administered as 0.5-mL IM injections 
into the deltoid muscle. The boost vaccination should be administered in the opposite deltoid from the 
prime vaccination. The third vaccination can be administered in either deltoid.
All subjects will receive a vaccination, according to randomization, on Day 1 (Groups 1 to 3) and on 
Day 29 (Group 1), Day 57 (Group 2) or Day 85 (Group 3) at the following dose levels:

Ad26.ZEBOV: 5x1010 vp, supplied in a single use vial (0.5 mL extractable);

MVA-BN-Filo: 1x108
Inf
U
(nominal titer; target fill is 1.9x108
Inf U per dose, 
range: 1.27-2.67x108 Inf U), supplied in a single use vial (0.5 mL extractable);

Placebo: 0.9% saline (0.5 mL extractable).
At selected sites, approximately 90 healthy adult subjects in Cohort 1 (Groups 1 and 2) will receive a 
third vaccination with Ad26.ZEBOV at 5x1010 vp or placebo at least 1 year post prime vaccination
(substudy).
Subjects will remain at the site for a total of 60 (±15) minutes (after prime and boost vaccinations) or 
30 (±15) minutes (after the third vaccination) post-vaccination to monitor for the development of any 
acute reactions, or longer if deemed necessary by the investigator (eg, in case of grade 3 adverse events).

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
24
Status: Approved, Date: 4 May 2017
Criteria for postponement of vaccination at the scheduled time for vaccine administration and 
contraindications to boost and third vaccinations have been defined and will be applied by the investigator
(not including those occurring because of study hold).
SAFETY EVALUATIONS
Safety evaluations will be performed as specified in the Time and Events Schedule. 
Safety will be assessed by collection of solicited local and systemic adverse events (reactogenicity), 
unsolicited adverse events, serious adverse events, and IREs. The subjects will be closely observed by 
study-site personnel for the first 30 (±10) minutes after each vaccination, and again at 60 (±15) minutes 
after prime and boost vaccinations, and any unsolicited, solicited local or systemic adverse events will be 
documented during this period. Upon discharge from the site, subjects will receive a diary, a thermometer 
and a ruler to measure body temperature and solicited local reactions. Subjects will be instructed to record
solicited local and systemic adverse events in the diary in the evening after each vaccination and then 
daily for the next 7 days at approximately the same time each day. Diaries should be completed at home 
by the subject (or parent, legal guardian or caregiver, as applicable). For illiterate subjects or those having 
difficulty completing the diary independently, the sites will make arrangements to have the diary 
completed according to their local practice. The investigator will document unsolicited adverse events 
from signing of the ICF/assent onwards until 42 days post-last vaccination (excluding the third 
vaccination), and again from the day of the third vaccination until 28 days thereafter for subjects in the 
Cohort 1 substudy (note: events that started before the third vaccination but are still present at the time of 
third vaccination should also be recorded). The investigator will document serious adverse events and 
IREs from signing of the ICF/assent onwards until the end of the study. The primary (or secondary for 
Cohort 1 substudy) endpoints are adverse events, serious adverse events, IREs, and solicited local and 
systemic adverse events. Adverse events that are ongoing at 42 days post-last vaccination (excluding third 
vaccination), or at 28 days post third vaccination for subjects in the Cohort 1 substudy, will be followed 
until resolution or stabilization. 
Other safety assessments include an electrocardiogram (ECG; for subjects ≥18 years of age, performed at 
screening), physical examination, vital signs (blood pressure, pulse/heart rate, body temperature), clinical 
laboratory and pregnancy testing.
The investigators, together with the sponsor’s medical monitor, will be responsible for the safety 
monitoring of the study, and will halt vaccination of further subjects in case any of the pre-specified 
pausing rules have been met. 
IMMUNOGENICITY EVALUATIONS
The investigator will collect samples for immunogenicity assessments as specified in the Time and Events 
Schedule, for evaluation of secondary and exploratory endpoints. Samples to assess humoral responses 
will be taken from all subjects; samples to assess cellular immune responses will be taken from subjects at 
selected sites with the capabilities to process peripheral blood mononuclear cells (PBMC) (targeted at 
165 subjects [138 Ad26.ZEBOV and MVA-BN-Filo, and 27 placebo] in Cohort 1 and 33 subjects 
[28 Ad26.ZEBOV and MVA-BN-Filo, and 5 placebo] in each of the other cohorts). PBMC sampling at 
selected sites will continue until the targeted number of subjects is reached. Samples to assess cellular 
immune responses are optional for subjects in the Cohort 1 substudy and may only be collected in a 
subset of subjects. Subjects giving informed consent for the study will be informed that their leftover
blood samples will be stored for potential future research. Subjects participating at selected sites where 
PBMC samples are collected will be asked explicitly to consent for potential future genetic research to be 
performed on PBMC samples. Subjects can withdraw consent for their samples to be used for future 
research at any time.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
25
Status: Approved, Date: 4 May 2017
STATISTICAL METHODS
An overall planned sample size of 1,056 subjects includes 880 subjects to receive Ad26.ZEBOV and 
MVA-BN-Filo to substantially contribute to an overall safety database of the Ad26.ZEBOV and 
MVA-BN-Filo prime-boost regimen. 
In Cohort 1, a total of 550 subjects are planned to be vaccinated with Ad26.ZEBOV and MVA-BN-Filo
across the vaccination schedules (220 in Groups 1 and 2, 110 in Group 3). In the other cohorts (2a, 2b, 
and 3), 55 subjects per vaccination schedule (Groups 1 and 2) are planned to be vaccinated with 
Ad26.ZEBOV and MVA-BN-Filo, or a total of 110 subjects per subpopulation.
In case a specific adverse event is not observed, the one-sided 97.5% upper confidence limit of the true 
incidence rate of this adverse event is less than 6.5%, 3.3%, 1.7%, 0.8%, 0.7% and 0.5%, for sample sizes 
of 55, 110, 220, 440, 550 and 880 subjects, respectively.
The primary analysis will be conducted when all subjects in Cohort 1 have completed the 6-month
post-boost visit or discontinued earlier, to aid in the assessment of which vaccination schedule will be the 
best candidate for future studies and implementation in the field. Study-site personnel, subjects and 
sponsor personnel involved in subject level data review will remain blinded until the last subject in that 
cohort has completed the study. Sponsor personnel involved in the conduct of the primary analysis and in 
making future decisions for the program will be unblinded to the data of Cohort 1, but will remain blinded
to the data of the other cohorts.
For the Cohort 1 substudy of subjects who received the third vaccination, an interim analysis may be 
performed when all subjects have completed the 6-month post third vaccination visit, or discontinued 
earlier.
In each cohort, after completion of the 6-month post-boost visit by all subjects, an interim analysis will be 
conducted on safety and selected immunogenicity data and the cohort will be unblinded to the sponsor.
Subjects who completed the 6-month post-prime visit prior to approval of Amendment 2 were required to 
attend the 6-month post-boost visit after approval of Amendment 2. 
The final analysis will be performed when all subjects have completed the last study-related visit or 
discontinued earlier (including subjects participating in the Cohort 1 substudy). 
Specific details will be provided in the Statistical Analysis Plan (SAP).
An IDMC will be established to monitor data on a regular basis to ensure the continuing safety of the 
subjects enrolled in the study.
Safety Analyses
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively 
(including 95% confidence intervals, if applicable). For each adverse event, the number and percentage of 
subjects who experience at least 1 occurrence of the given event will be summarized by group. 
Summaries, listings, datasets, or subject narratives may be provided, as appropriate, for those subjects 
who die, who discontinue study vaccine due to an adverse event, or who experience a severe or a serious 
adverse event. The most severe laboratory abnormalities following vaccination will be tabulated. 
Abnormalities in vital signs and physical examination following vaccination will be tabulated by most 
severe abnormality grade. Similar safety summaries will be created for the subjects who received a third 
vaccination.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
26
Status: Approved, Date: 4 May 2017
Immunogenicity Analyses 
Descriptive statistics (actual values and changes from baseline, including 95% confidence intervals, if 
applicable) will be calculated for continuous immunologic parameters at each time point analyzed. 
Graphical representations of changes in immunologic parameters will be prepared, as applicable. 
Frequency tabulations will be calculated for discrete (qualitative) immunologic parameters at each time 
point analyzed. In addition, differences between the vaccination schedules will be described at the 21-day 
post-boost, 6-month post-boost, and Day 365 visits. Similar summaries will be provided for the time 
points after the third vaccination for the Cohort 1 substudy population.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
27
Status: Approved, Date: 4 May 2017
TIME AND EVENTS SCHEDULE
Cohort 1 (Groups 1-3) and Cohorts 2a and 2b (Groups 1-2)
Group
Screening 
Phasea
(≤8 weeks)
Vaccination Phase and Post-vaccination Phaseb
Long-term 
Follow-up Phaseb,c
Group 1 (Cohorts 1, 2a, 2b)
D1
D2-D7
D8
-
D29
D30-D35
D36
D50
D71d
D209
D365
Group 2 (Cohorts 1, 2a, 2b)
D15
D57
D58-D63
D64
D78 
D99d
D237
Group 3 (Cohort 1 only)
D15
D85
D86-D91
D92
D106
D127d
D265
Study procedures
Prime
+7d pp
+14d pp
Boost
+7d pb
+21d pb
+42d pb
+6m pbe
+1y pp
Screening/Administrative
Informed consent/assentf
X
Inclusion/exclusion criteria
Xg
Medical history and 
demographics
X
Prestudy therapiesh
X
Serum pregnancy testi
X
HIV-1/2 serology (Cohorts 1 and 
2b only)
X
Follicle-stimulating hormone 
(FSH)j
X
Test of Understanding (TOU) f
X
Check clinical status + available 
data
Xk
Randomization
X
Study Vaccine Administrationl
▲
▼
Safety Assessments
Urine Pregnancy testi
  Xm
  Xm
Electrocardiogram (ECG)n
X
Physical examinationo
X
  Xm
X
  Xm
X
X
X
X
X
Vital signsp
X
  Xm
  Xm
Distribution of subject diary 
X
X
Completion of diary at homeq
X
X
Review of diary by site staff
X
X
Adverse eventsr
Continuous
Serious adverse events and 
immediate reportable eventss
Continuous
Concomitant medications
X
X
X
X
Xt
X
X
X
X
X
Xu
Xu

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
28
Status: Approved, Date: 4 May 2017
Group
Screening 
Phasea
(≤8 weeks)
Vaccination Phase and Post-vaccination Phaseb
Long-term 
Follow-up Phaseb,c
Group 1 (Cohorts 1, 2a, 2b)
D1
D2-D7
D8
-
D29
D30-D35
D36
D50
D71d
D209
D365
Group 2 (Cohorts 1, 2a, 2b)
D15
D57
D58-D63
D64
D78 
D99d
D237
Group 3 (Cohort 1 only)
D15
D85
D86-D91
D92
D106
D127d
D265
Study procedures
Prime
+7d pp
+14d pp
Boost
+7d pb
+21d pb
+42d pb
+6m pbe
+1y pp
Clinical Laboratory Assessments
Chemistry, hematology (10 mL)v
X
  Xm
X
  Xm
X
CD4+ cell count (2 mL)w
  Xw
  Xw
  Xw
  Xw
Urinalysis
X 
Immunogenicity Assessmentsx
Blood sampling (serum) for 
assessment of humoral immune 
responses (10 mL)
  Xm
Xt
  Xm
Xy
X
X
X
Blood sampling (PBMC) for 
assessment of cellular immune 
responses (40 or 20 mL)z
  Xm
Xt
  Xm
Xy
X
X
X
Approximate Blood 
Volumesaawith [without] PBMC
- By visit (mL)bb
Cohort 1 (Group 1)
Cohort 1 (Groups 2 and 3) 
Cohort 2a
Cohort 2b (12- to 17-year old)
10
10
12
10
60 [20]
60 [20]
62 [22]
40 [20]
10
10
10
10
0
50t [10]
0
0
60 [20]
60 [20]
62 [22]
40 [20]
60 [20]
60 [20]
60 [20]
10
50 [10]
50 [10]
50 [10]
30 [10]
0
0
2
0
50 [10]
50 [10]
50 [10]
30 [10]
50 [10]
50 [10]
50 [10]
30 [10]
- Cumulative (mL)bb
Cohort 1 (Group 1) 
Cohort 1 (Groups 2 and 3)
Cohort 2a
Cohort 2b (12- to 17-year old)
10
10
12
10
70 [30]
70 [30]
74 [34]
50 [30]
80 [40]
80 [40]
84 [44]
60 [40]
80 [40]
130t [50]
84 [44]
60 [40]
140 [60]
190 [70]
146 [66]
100 [60]
200 [80]
250 [90]
206 [86]
110 [70]
250 [90]
300 [100]
256 [96]
140 [80]
250 [90]
300 [100]
258 [98]
140 [80]
300 [100]
350 [110]
308 [108]
170 [90]
350 [110]
400 [120]
358 [118]
200 [100]
▲ Ad26.ZEBOV 5x1010 vp or placebo ▼ MVA-BN-Filo 1x108 Inf U or placebo
d pp: days post-prime; d pb: days post-boost; m pb: months post-boost; y pp: year post-prime
NOTE: In case of early withdrawal from the study, early withdrawal assessments (ie, physical examination and immunogenicity assessments for serum and PBMCs)
should be obtained. 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.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
29
Status: Approved, Date: 4 May 2017
a.
Screening may be split into multiple days or visits. Retesting of values (eg, safety laboratory) that lead to exclusion is allowed once using an unscheduled visit 
during the screening phase. The safety laboratory assessments at screening are to be performed within 28 days prior to the prime vaccination (including Day 1 
before vaccination) and may be repeated if they fall outside this time window. If rescreening is required, all screening procedures (except TOU) should be 
repeated. Similarly, subjects that are rescreened due to the pause must have new safety laboratory assessments (including HIV, FSH [if applicable], ECG, 
hematology, biochemistry, urinalysis, vital signs and physical examination) within 28 days of the prime vaccination. The TOU does not need to be repeated.
b.
For subjects who receive a late boost vaccination, the timings of the next post-boost visits will be determined relative to the actual day of the boost vaccination.
c.
For each cohort, all subjects will be followed up in a blinded manner by the site for the collection of serious adverse event information, immediate reportable 
events, and for blood draws for immunogenicity assessments until the last subject in that cohort has completed the study. Any subject who completed either the 
6-month post-prime and/or the Day 365 visit prior to approval of Amendment 2 was required to attend the 6-month post-boost and the Day 365 visit after 
approval of Amendment 2. At selected sites in Cohort 1 (Groups 1 and 2), a third vaccination with Ad26.ZEBOV will be administered at least 1 year post 
prime to subjects who consent to this (for details, refer to Cohort 1 Substudy Time and Events Schedule).
d.
In addition to the assessments scheduled for the 42-day post-boost visit, subjects will be instructed to contact the investigator before the next visit if they 
experience any adverse event or intercurrent illness that they perceive as relevant and/or can be possibly related to study vaccine in their opinion. All subjects 
within a cohort will be followed in a blinded manner by the site until the last subject in that cohort has completed the study. Any subject who completed either 
the 6-month post-prime and/or the Day 365 visit prior to approval of Amendment 2 was required to attend the 6-month post-boost and the Day 365 visit after 
approval of Amendment 2.
e.
Subjects who completed the 6-month post-prime visit (which has been replaced with the 6-month post-boost visit per protocol Amendment 2) prior to approval 
of Amendment 2 were required to also attend the 6-month post-boost visit after approval of Amendment 2.
f.
Signing of the informed consent form (ICF) and/or assent needs to be done before the first study-related activity. After reading but before signing the 
ICF/assent, the TOU will be administered. 
g.
The investigators should ensure that all study enrollment criteria have been met at the end of the screening phase. Minimum criteria for the availability of 
documentation supporting the eligibility criteria are described in Section 17.4.
h.
Prestudy therapies up to 30 days prior to the start of screening and previous vaccinia/smallpox vaccination at any time prior to study entry must be recorded in 
the case report form (CRF). HIV-therapy should be recorded for HIV-infected subjects. 
i.
Only for women of childbearing potential.
j.
Only for women >45 years of age with amenorrhea for less than 2 years or ≤45 years of age with amenorrhea for more than 6 months.
k.
If a subject’s clinical status changes (including available laboratory results or the receipt of additional medical records) after screening so the subject no longer 
meets the eligibility criteria, the subject should be excluded from further participation in the study.
l.
After the prime and boost vaccinations, subjects will remain at the site for a total of 60 (±15) minutes post-vaccination to monitor for the development of any 
acute reactions, or longer if deemed necessary by the investigator. Solicited and unsolicited adverse events emerging during the observation period at the site 
will be recorded in the CRF.
m. Prior to study vaccine administration. 
n.
A single, 12-lead ECG (supine) after 5 minutes of rest will be performed for subjects ≥18 years of age (Cohorts 1 and 2a) at screening and interpreted locally. 
Additional ECG monitoring may be performed at other time points during the study if clinically indicated. If blood sampling or vital sign measurements are 
scheduled at the same time point as the ECG recording, the procedures should preferably be performed in the following order: vital signs, ECG, blood draw.
o.
A full physical examination, including height and body weight, will be carried out at screening. A genitourinary examination is not required. At other visits, an 
abbreviated, symptom-directed examination will be performed as indicated by the investigator. 
p.
Includes blood pressure, pulse/heart rate (at rest) and body temperature.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
30
Status: Approved, Date: 4 May 2017
q.
Subjects will use the subject diary to document solicited local and systemic adverse events (reactogenicity) in the evening after prime and boost vaccination and 
then daily for the next 7 days at approximately the same time each day. Diaries should be completed at home by the subject. For illiterate subjects or those 
having difficulty completing the diary independently, the sites will make arrangements to have the diary completed according to their local practice.
r.
Pregnancies will be reported from signing of the ICF until the end of the study.
s.
For reporting of immediate reportable events, refer to Section 12.3.3.
t.
Day 15 visit only for subjects in Groups 2 and 3 from Cohort 1.
u.
Concomitant therapies must be recorded up to 42 days after the last vaccination. Thereafter, concomitant therapies should only be recorded if given in 
conjunction with serious adverse events and immediate reportable events.
v.
Approximate blood volume expected to be drawn per visit for clinical laboratory assessments: 10 mL for Cohorts 1, 2a and 2b.
w.
Only for HIV-infected subjects.
x.
Blood volumes for immunogenicity assessments are indicated in Table 7.
y.
Immunogenicity assessments on the 7-day post-boost visit will only be performed for Cohorts 1 and 2a, not for Cohort 2b.
z.
PBMC samples will be obtained from subjects at selected sites with the capabilities to process PBMC samples (targeted at 165 subjects in Cohort 1 and 
33 subjects in each of the other cohorts). Approximate blood volume for cellular immune response assessments: 40 mL for Cohorts 1 and 2a, but only 20 mL 
for Cohort 2b.
aa. The approximate blood volume excludes repeat or unscheduled samples taken for safety reasons or for technical issues with the samples.
bb. Values in square brackets indicate the approximate or cumulative blood volume without PBMC samples.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
31
Status: Approved, Date: 4 May 2017
Pediatric Cohort 3 (Groups 1-2)
Group
Screening 
Phasea
(≤8 weeks)
Vaccination Phase and Post-vaccination Phase
Long-term 
Follow-up Phaseb
Group 1
D1
D2-D7
D8
D29
D30-D35
D36
D50
D71c
D209
D365
Group 2
D57
D58-D63
D64
D78 
D99c
D237
Study procedures
Prime
+7d pp
Boost
+7d pb
+21d pb
+42d pb
+6m pbd
+1y pp
Screening/Administrative
Informed consent/assente
X
Inclusion/exclusion criteria
Xf
Medical history and demographics
X
Prestudy therapiesg
X
Serum pregnancy testh
X
HIV 1/2 serology 
X
Test of Understanding (TOU) e,i
X
Prevaccination symptoms
X
Check clinical status + available 
data
Xj
Randomization
X
Study Vaccine Administrationk
▲
▼
Safety Assessments
Urine Pregnancy testh
Xl
Xl
Body length/height and weight
X
X
Physical examinationm
X
Xl
X
Xl
X
X
X
X
X
Vital signsn
X
Xl
X
Xl
X
X
Distribution of subject diary 
X
X
Completion of diary at homeo
X
X
Review of diary by site staff
X
X
Adverse eventsp
Continuous
Serious adverse events and 
immediate reportable eventsq
Continuous
Concomitant medications
X
X
X
X
X
X
X
X
X
Xr
Xr
Clinical Laboratory Assessments
Chemistry, hematology
(2 to 6 mL)s
X
Xl
X
Xl
X
Urinalysis
X 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
32
Status: Approved, Date: 4 May 2017
Group
Screening 
Phasea
(≤8 weeks)
Vaccination Phase and Post-vaccination Phase
Long-term 
Follow-up Phaseb
Group 1
D1
D2-D7
D8
D29
D30-D35
D36
D50
D71c
D209
D365
Group 2
D57
D58-D63
D64
D78 
D99c
D237
Study procedures
Prime
+7d pp
Boost
+7d pb
+21d pb
+42d pb
+6m pbd
+1y pp
Immunogenicity Assessmentst
Blood sampling (serum) for 
assessment of humoral immune 
responses (2.2 to 5 mL)t
Xl
Xl
X
X
X
Blood sampling (PBMC) for 
assessment of cellular immune 
responses (3 to 10 mL)u
Xl
X
X
X
Approximate Blood Volumesv
with [without] PBMC (for 
Immunogenicity Analyses)
- By visit (mL)w
Cohort 3 (9- to 11-year old) 
15 [5]
5
15 [5]
15 [5]
15 [5]
Cohort 3 (6- to 8-year old) 
8.5 [2.5]
2.5
8.5 [2.5]
8.5 [2.5]
8.5 [2.5]
Cohort 3 (4- to 5-year old)
6.5 [2.5]
2.5
6.5 [2.5]
6.5 [2.5]
6.5 [2.5]
- Cumulative (mL)w
Cohort 3 (9- to 11-year old)
15 [5]
20 [10]
35 [15]
50 [20]
65 [25]
Cohort 3 (6- to 8-year old)
8.5 [2.5]
11 [5]
19.5 [7.5]
28 [10]
36.5 [12.5]
Cohort 3 (4- to 5-year old)
6.5 [2.5]
9 [5]
15.5 [7.5]
22 [10]
28.5 [12.5]
▲ Ad26.ZEBOV 5x1010 vp or placebo ▼ MVA-BN-Filo 1x108 Inf U or placebo
d pp: days post-prime; d pb: days post-boost; m pb: months post-boost; y pp: year post-prime
NOTE: In case of early withdrawal from the study, early withdrawal assessments (ie, physical examination and immunogenicity assessments for serum and PBMCs)
should be obtained. 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.
Screening may be split into multiple days or visits. Retesting of values (eg, safety laboratory) that lead to exclusion is allowed once using an unscheduled visit 
during the screening period, provided there is an alternative explanation for the out of range value. The safety laboratory assessments at screening are to be 
performed within 28 days prior to the prime vaccination (including Day 1 before vaccination) and may be repeated if they fall outside this time window. If 
rescreening is required, all screening procedures (except TOU) should be repeated.
b.
For each cohort, all subjects will be followed up in a blinded manner by the site for the collection of serious adverse event information, immediate reportable 
events, and for blood draws for immunogenicity assessments until the last subject in that cohort has completed the study. Any subject who completed either the 
6-month post-prime and/or the Day 365 visit prior approval of Amendment 2 was required to attend the 6-month post-boost and the Day 365 visit after 
approval of Amendment 2.
c.
In addition to the assessments scheduled for the 42-day post-boost visit, subjects will be instructed to contact the investigator before the next visit if they 
experience any adverse event or intercurrent illness that they perceive as relevant and/or can be possibly related to study vaccine in their opinion. All subjects 
within a cohort will be followed in a blinded manner by the site until the last subject in that cohort has completed the study. Any subject who completed either 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
33
Status: Approved, Date: 4 May 2017
the 6-month post-prime and/or the Day 365 visit prior approval of Amendment 2 was required to attend the 6-month post-boost and the Day 365 visit after 
approval of Amendment 2.
d.
Subjects who completed the 6-month post-prime visit (which has been replaced with the 6-month post-boost visit per protocol Amendment 2) prior to approval 
of Amendment 2 were required to also attend the 6-month post-boost visit after approval of Amendment 2.
e.
Signing of the informed consent form (ICF) and/or assent needs to be done before the first study-related activity. After reading but before signing the 
ICF/assent, the TOU will be administered.  
f.
The investigators should ensure that all study enrollment criteria have been met at the end of the screening phase. Minimum criteria for the availability of
documentation supporting the eligibility criteria are described in Section 17.4.
g.
Prestudy therapies up to 30 days prior to the start of screening must be recorded in the case report form (CRF).
h.
Only for female subjects of childbearing potential. 
i.
Test of Understanding (TOU) should be administered to the parent or guardian who gave consent, and to older children who provided assent as per local 
regulations and practice.
j.
If a subject’s clinical status changes (including available laboratory results or the receipt of additional medical records) after screening so the subject no longer 
meets the eligibility criteria, the subject should be excluded from further participation in the study.
k.
After each vaccination, subjects will remain at the site for a total of 60 (±15) minutes post-vaccination to monitor for the development of any acute reactions, or 
longer if deemed necessary by the investigator. Solicited and unsolicited adverse events emerging during the observation period at the site will be recorded in 
the CRF.
l.
Prior to study vaccine administration.
m. A full physical examination, including height and body weight, will be carried out at screening. A genitourinary examination is not required. At other visits, an 
abbreviated, symptom-directed examination will be performed as indicated by the investigator.
n.
Includes blood pressure, pulse/heart rate (at rest) and body temperature.
o.
Subjects will use the subject diary to document solicited local and systemic adverse events (reactogenicity) in the evening after each vaccination and then daily 
for the next 7 days at approximately the same time each day. Diaries should be completed at home by the subject (or parent, legal guardian or caregiver, as 
applicable). For illiterate subjects or those having difficulty completing the diary independently, the sites will make arrangements to have the diary completed 
according to their local practice.
p.
Pregnancies will be reported from signing of the ICF until the end of the study.
q.
For reporting of immediate reportable events, refer to Section 12.3.3.
r.
Concomitant therapies must be recorded up to 42 days after the last vaccination. Thereafter, concomitant therapies should only be recorded if given in 
conjunction with serious adverse events and immediate reportable events. 
s.
Approximate blood volumes for clinical laboratory assessments as per site Standard Operating Procedure.
t.
Blood volumes for immunogenicity assessments are indicated in Table 7.
u.
PBMC samples will be obtained from subjects at selected sites with the capabilities to process PBMC samples (targeted at 165 subjects in Cohort 1 and 
33 subjects in each of the other cohorts).
v.
The approximate blood volumes exclude safety blood testing, repeat or unscheduled samples taken for safety reasons or for technical issues with the samples. 
w.
Values in square brackets indicate the approximate or cumulative blood volume without PBMC samples.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
34
Status: Approved, Date: 4 May 2017
ADDITIONAL TIME AND EVENTS SCHEDULE
Subjects Who Do Not Receive a Boost Vaccination Because of a Study Pause
Group
Screening 
Phasea
(≤8 weeks)
Vaccination Phase and Post-vaccination Phase
Long-term Follow-up Phaseb
Group 1
D1
D2-D7
D8c
-
D90
D180
D270
D365
Group 2
D15c
Group 3
D15c
Study procedures
Prime
+7d pp
+14d pp
+3m ppd
+6m pp
+9m ppd
+1y pp
Screening/Administrative
Informed consent/assente
X
Inclusion/exclusion criteria
Xf
Medical history and 
demographics
X
Prestudy therapiesg
X
Serum pregnancy testh
X
HIV-1/2 serology (Cohorts 1 and 
2b only)
X
Follicle-stimulating hormone 
(FSH)i
X
Test of Understanding (TOU)e
X
Check clinical status + available 
data
Xj
Randomization
X
Study Vaccine Administrationk
▲
Safety Assessments
Urine Pregnancy testh
Xl
Electrocardiogram (ECG)m
X
Physical examinationn
X
Xl
X
Xo
X
Xo
X
Vital signsp
X
Xl
Xo
Xo
Distribution of subject diary 
X
Completion of diary at homeq
X
Review of diary by site staff
X
Adverse eventsr
Continuous
Serious adverse events and 
immediate reportable eventss
Continuous
Concomitant medications
X
X
X
X
Xt
Xu
Xu
Xu
Xu

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
35
Status: Approved, Date: 4 May 2017
Group
Screening 
Phasea
(≤8 weeks)
Vaccination Phase and Post-vaccination Phase
Long-term Follow-up Phaseb
Group 1
D1
D2-D7
D8c
-
D90
D180
D270
D365
Group 2
D15c
Group 3
D15c
Study procedures
Prime
+7d pp
+14d pp
+3m ppd
+6m pp
+9m ppd
+1y pp
Clinical Laboratory Assessments
Chemistry, hematology (10 mL)v
X
Xl
X
Urinalysis
X 
Immunogenicity Assessmentsw
Blood sampling (serum) for 
assessment of humoral immune 
responses (10 mL)
Xl
Xt
X
X
Blood sampling (PBMC) for 
assessment of cellular immune 
responses (40 mL)x
Xl
Xt
X
X
Approximate Blood Volumesy
with [without] PBMC
- By visit (mL)z
Cohort 1 (Group 1) 
Cohort 1 (Groups 2 and 3) 
10
10
60 [20]
60 [20]
10
10
0
50t [10]
50 [10]
50 [10]
50 [10]
50 [10]
- Cumulative (mL)z
Cohort 1 (Group 1) 
Cohort 1 (Groups 2 and 3)
10
10
70 [30]
70 [30]
80 [40]
80 [40]
80 [40]
130t [50]
130 [50]
180 [60]
180 [60]
230 [70]
▲ Ad26.ZEBOV 5x1010 vp or placebo ▼ MVA-BN-Filo 1x108 Inf U or placebo
d pp: days post-prime; m pp: months post-prime; y pp: year post-prime
NOTE: In case of early withdrawal from the study, early withdrawal assessments (ie, physical examination and immunogenicity assessments for serum and PBMCs)
should be obtained. 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.
Screening may be split into multiple days or visits. Retesting of values (eg, safety laboratory) that lead to exclusion is allowed once using an unscheduled visit 
during the screening phase. The safety laboratory assessments at screening are to be performed within 28 days prior to the prime vaccination (including Day 1 
before vaccination) and may be repeated if they fall outside this time window.
b.
All subjects will be followed up in a blinded manner by the site for the collection of serious adverse event information, immediate reportable events, and for 
blood draws for immunogenicity assessments until Day 365.
c.
In addition to the assessments scheduled for the 7-day post-prime visit (or 14-day post-prime visit for subjects in Group 2 and 3 of Cohort 1), subjects will be 
instructed to contact the investigator before the next visit if they experience any adverse event or intercurrent illness that they perceive as relevant and/or can be 
possibly related to study vaccine in their opinion. 
d.
Information for these visits may be collected either by telephone contact, visit to the site or by a home visit, according to local practice. 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
36
Status: Approved, Date: 4 May 2017
e.
Signing of the informed consent form (ICF) and/or assent needs to be done before the first study-related activity. After reading but before signing the 
ICF/assent, the TOU will be administered. 
f.
The investigators should ensure that all study enrollment criteria have been met at the end of the screening phase. Minimum criteria for the availability of 
documentation supporting the eligibility criteria are described in Section 17.4.
g.
Prestudy therapies up to 30 days prior to the start of screening and previous vaccinia/smallpox vaccination at any time prior to study entry must be recorded in 
the case report form (CRF). 
h.
Only for women of childbearing potential.
i.
Only for women >45 years of age with amenorrhea for less than 2 years or ≤45 years of age with amenorrhea for more than 6 months.
j.
If a subject’s clinical status changes (including available laboratory results or the receipt of additional medical records) after screening so the subject no longer 
meets the eligibility criteria, the subject should be excluded from further participation in the study.
k.
After each vaccination, subjects will remain at the site for a total of 60 (±15) minutes post-vaccination to monitor for the development of any acute reactions, or 
longer if deemed necessary by the investigator. Solicited and unsolicited adverse events emerging during the observation period at the site will be recorded in 
the CRF.
l.
Prior to study vaccine administration. 
m. A single, 12-lead ECG (supine) after 5 minutes of rest will be performed for subjects ≥18 years of age at screening and interpreted locally. Additional ECG 
monitoring may be performed at other time points during the study if clinically indicated. If blood sampling or vital sign measurements are scheduled at the 
same time point as the ECG recording, the procedures should preferably be performed in the following order: vital signs, ECG, blood draw.
n.
A full physical examination, including height and body weight, will be carried out at screening. A genitourinary examination is not required. At other visits, an 
abbreviated, symptom-directed examination will be performed as indicated by the investigator. 
o.
Physical examination and vital signs assessments are optional at these visits.
p.
Includes blood pressure, pulse/heart rate (at rest) and body temperature.
q.
Subjects will use the subject diary to document solicited local and systemic adverse events (reactogenicity) in the evening after each vaccination and then daily 
for the next 7 days at approximately the same time each day. Diaries should be completed at home by the subject. For illiterate subjects or those having 
difficulty completing the diary independently, the sites will make arrangements to have the diary completed according to their local practice.
r.
Non-serious adverse events will be reported until the 42-day post-last vaccination visit. Pregnancies will be reported from signing of the ICF until the end of 
the study.
s.
For reporting of immediate reportable events, refer to Section 12.3.3.
t.
Day 15 visit only for subjects in Groups 2 and 3 from Cohort 1.
u.
Concomitant therapies must be recorded up to 42 days after the last vaccination. Thereafter, concomitant therapies should only be recorded if given in 
conjunction with serious adverse events and immediate reportable events.
v.
Approximate blood volume expected to be drawn per visit for clinical laboratory assessments: 10 mL for Cohort 1.
w.
Blood volumes for immunogenicity assessments are indicated in Table 7.
x.
PBMC samples will be obtained from subjects at selected sites with the capabilities to process PBMC samples (targeted at 165 subjects in Cohort 1). 
Approximate blood volume for cellular immune response assessments: 40 mL for Cohort 1.
y.
The approximate blood volume excludes repeat or unscheduled samples taken for safety reasons or for technical issues with the samples. 
z.
Values in square brackets indicate the approximate or cumulative blood volume without PBMC samples.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
37
Status: Approved, Date: 4 May 2017
COHORT 1 SUBSTUDY TIME AND EVENTS SCHEDULE
Subjects at Selected Sites Receiving a Third Vaccination (Cohort 1, Groups 1-2)
Vaccination Phase and Post-vaccination Phase
Long-term Follow-up Phasea
Groups 1 & 2b
1 Year Post 
Prime
+ 3 months
D2-D7 Post 3rd
Vaccination
D5 Post 3rd
Vaccination
D8 Post 3rd
Vaccination
D22 Post 3rd
Vaccination
D180 Post 3rd
Vaccination
D365 Post 3rd
Vaccination
Study procedures
3rd Vaccination
+4d p3v
+7d p3v
+21d p3v
+6m p3v
+1y p3v
Screening/Administrative
Informed consentc
X
Study vaccine administration
▲d
Safety assessments
Urine pregnancy teste
Xf
Physical examinationg
Xf
X
X
X
Xh
Xh
Vital signsi
Xf
Distribution of subject diary 
X
Completion of diary at homej
X
Review of diary by site staff
X
Adverse eventsk
Continuous until 28 days after the third vaccinationa,l
Serious adverse events and immediate 
reportable events m
Continuousa,l
Concomitant medications
X
X
X
X
Xn
Xn
Clinical Laboratory Assessments
Chemistry, hematology (10 mL)o
Xf
X
Immunogenicity Assessmentsp
Blood sampling (serum) for assessment 
of humoral immune responses (10 mL)
Xf
X
X
X
X
X
Blood sampling (PBMC) for assessment 
of cellular immune responses (40 mL)q
Xf
X
X
Approximate Blood Volumes with 
[without] PBMCr
- By visit (mL)r
Cohort 1 (Group 1 and 2)
60 [20]
10
20
50 [10]
10
50 [10]
- Cumulative (mL)r
Cohort 1 (Group 1 and 2)
60 [20]
70 [30]
90 [50]
140 [60]
150 [70]
200 [80]
▲ Ad26.ZEBOV 5x1010 vp or placebo
d p3v: days post third vaccination; m p3v: months post third vaccination; y p3v: year post third vaccination

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
38
Status: Approved, Date: 4 May 2017
NOTE: In case of early withdrawal from the study, early withdrawal assessments (ie, physical examination and immunogenicity assessments for serum) should be 
obtained. 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.
NOTE: The day of administration of the third vaccination is Day 1 of the Cohort 1 substudy. Similarly, D2 Post 3rd vaccination is the second day of the Cohort 1 
substudy, ie, 1 day after the third vaccination.
a.
All subjects will be followed up in a blinded manner by the site for the collection of serious adverse event information, immediate reportable events, and for 
blood draws for immunogenicity assessments until the last subject in that cohort has completed the study. 
b.
Subjects eligible for the third vaccination are members of Cohort 1 (Groups 1 or 2) who consented to participate in the substudy. Approximately 90 subjects 
from Cohort 1 will be recruited at selected sites. For subjects who receive the third vaccination, the timings of the next post third vaccination visits will be 
determined relative to the actual day of the third vaccination.
c.
Informed consent form to enter in the Cohort 1 substudy must be provided and signed before the first substudy-related activity. 
d.
After the third vaccination, subjects will remain at the site for a total of 30 (±15) minutes post-vaccination to monitor for the development of any acute 
reactions, or longer if deemed necessary by the investigator. Solicited and unsolicited adverse events emerging during the observation period at the site will be 
recorded in the case report form (CRF).
e.
Only for women of childbearing potential.
f.
Prior to study vaccine administration.
g.
An abbreviated, symptom-directed examination will be performed as indicated by the investigator. 
h.
During the long-term follow-up, a physical examination should only be performed when related to serious adverse events and immediate reportable events.
i.
Includes blood pressure, pulse/heart rate (at rest) and body temperature.
j.
Subjects will use the subject diary to document solicited local and systemic adverse events (reactogenicity) in the evening after the third vaccination and then 
daily for the next 7 days at approximately the same time each day. Diaries should be completed at home by the subject. For illiterate subjects or those having 
difficulty completing the diary independently, the sites will make arrangements to have the diary completed according to their local practice.
k.
Non-serious adverse events will be reported until 28 days after the third vaccination. Pregnancies will be reported from signing of the informed consent form 
(ICF) until the end of the study.
l.
Subjects will be instructed to contact the investigator before the next visit if they experience any adverse event or intercurrent illness that they perceive 
as relevant and/or can be possibly related to study vaccine in their opinion. All subjects within a cohort will be followed in a blinded manner by the site until 
the last subject in that cohort has completed the study. 
m. For reporting of immediate reportable events, refer to Section 12.3.3.
n.
Concomitant therapies must 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 immediate reportable events.
o.
Approximate blood volume expected to be drawn per visit for clinical laboratory assessments: 10 mL.
p.
Blood volumes for immunogenicity assessments are indicated in Table 7.
q.
These samples are optional and may only be collected in a subset of subjects in the substudy.
r.
The approximate blood volume excludes repeat or unscheduled samples taken for safety reasons or for technical issues with the samples. 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
39
Status: Approved, Date: 4 May 2017
ABBREVIATIONS
Adxx
adenovirus serotype xx (vector)
Ad26.ZEBOV
adenovirus serotype 26 expressing the Ebola virus Mayinga glycoprotein
AIDS
acquired immunodeficiency syndrome
ARV
antiretroviral agent
β-hCG
β-human chorionic gonadotropin
BMI
body mass index
BN
Bavarian Nordic
CDC
Centers for Disease Control and Prevention 
CRF
case report form 
DMID
Division of Microbiology and Infectious Diseases
DNA
deoxyribonucleic acid
EBOV
Ebola virus
ECG
electrocardiogram
eDC
electronic data capture
EDTA
ethylenediaminetetraacetic acid
ELISA
enzyme-linked immunosorbent assay
ELISpot
enzyme-linked immunospot 
EU
European Union
FSH
follicle stimulating hormone
GCP
Good Clinical Practice
GMP
Good Manufacturing Practice
GP
glycoprotein
HAART
Highly Active Antiretroviral Therapy
HIV
human immunodeficiency virus
ICF
informed consent form
ICH
International Council for Harmonisation
ICS
intracellular cytokine staining
IDMC
Independent Data Monitoring Committee
IEC
Independent Ethics Committee
IFN-γ
interferon-gamma
Ig
immunoglobulin
IL
interleukin
IM
intramuscular(ly)
IMI
Innovative Medicines Initiative
Inf U
infectious units
INSERM
Institut National de la Santé et de la Recherche Médicale
IRB
Institutional Review Board
IRE
immediate reportable event
IWRS
interactive web response system
kb
kilobase
MARV
Marburg virus
MedDRA
Medical Dictionary for Regulatory Activities
MVA
Modified Vaccinia Ankara
MVA-BN-Filo
Modified Vaccinia Ankara Bavarian Nordic vector expressing multiple filovirus proteins
NHP
nonhuman primate
NP
nucleoprotein
PBMC
peripheral blood mononuclear cell
PQC
Product Quality Complaint
RNA
ribonucleic acid
SAP
Statistical Analysis Plan
SUDV
Sudan virus
SUSAR
suspected unexpected serious adverse reaction
TAFV
Tai Forest virus
TCID50
50% tissue culture infective dose
THAM
tris (hydroxymethyl)-amino methane
TNF-α
tumor necrosis factor-α

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
40
Status: Approved, Date: 4 May 2017
TOU
test of understanding
US
United States
VISP
vaccine-induced seropositivity
vp
viral particles
WHO
World Health Organization
DEFINITIONS OF TERMS
Study vaccine
Ad26.ZEBOV, MVA-BN-Filo or placebo.
Blinded study vaccine 
administrator
A blinded trained study nurse, medical doctor, or otherwise qualified health care 
provider.
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. 
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.
End of the study (for a 
subject)
For subjects in the Cohort 1 substudy: after completion of all assessments at the 
1-year post third vaccination visit.
For all other subjects: after completion of all assessments at the 6-month post-boost 
vaccination visit or at the Day 365 visit, whichever occurs later. 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
41
Status: Approved, Date: 4 May 2017
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 (BN), and in conjunction with 
an Innovative Medicines Initiative (IMI) consortium led by the Institut National de la Santé et de 
la Recherche Médicale (INSERM), is investigating the potential of a prophylactic Ebola vaccine 
regimen comprised of the following 2 candidate Ebola vaccines:
Ad26.ZEBOV is a monovalent vaccine expressing the full length Ebola virus (EBOV, formerly 
known as Zaire ebolavirus) Mayinga glycoprotein (GP), and is produced in the human cell line 
PER.C6®.
MVA-mBN226B, further referred to as Modified Vaccinia Ankara (MVA)-BN®-Filo, is a 
multivalent vaccine expressing the Sudan virus (SUDV) GP, the EBOV GP, the Marburg virus 
(MARV) Musoke GP, and the Tai Forest virus (TAFV, formerly known as Côte d’Ivoire
ebolavirus) nucleoprotein (NP), and is produced in chicken embryo fibroblast cells. The EBOV 
GP expressed by MVA-BN-Filo has 100% homology to the one expressed by Ad26.ZEBOV. 
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).14,15 A brief summary of the nonclinical and clinical information is provided below.
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 Ebola virus disease, which can induce 
severe hemorrhagic fever in humans and nonhuman primates (NHPs). Case fatality rates in Ebola 
disease range from 25% to 90% (average: 50%), according to the World Health Organization 
(WHO).27 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 an RNA-dependent 
RNA polymerase, which is carried into the cell together with the virus.11

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
42
Status: Approved, Date: 4 May 2017
Nonclinical Studies
1.1.1.
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 adenovirus serotype 26 (Ad26), Ad35 
and MVA-BN-Filo vectors expressing different Ebola and Marburg proteins. Full protection 
from Ebola virus disease 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 are ongoing, 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 Ebola virus disease outbreak in West Africa. 
Toxicology
A repeated-dose toxicity study in rabbits was performed with prime-boost combinations of 
Ad26.ZEBOV and MVA-BN-Filo. The different dose regimens were well tolerated when 
administered twice by intramuscular (IM) injection to New Zealand White rabbits with a 14-day 
interval period. Additionally, the objective was to assess the persistence, reversibility or delayed 
onset of any effects after a 14-day treatment-free period. In the heterologous prime-boost 
regimen, either vector or both were used to prime a filovirus-specific immune response and the 
other/same vector or both were used to boost the immune response 2 weeks later. All vaccine 
dosing regimens resulted in detectable EBOV GP-specific antibody titers. No significant 
toxicological effects (no adverse effects) were observed. The immune response was associated 
with transient increases in fibrinogen, C-reactive protein, 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.
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 
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.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
43
Status: Approved, Date: 4 May 2017
Clinical Studies
1.1.2.
1.1.2.1
Safety Profile of Ad26-based Vaccines
To date, no human clinical studies have been completed with Ad26.ZEBOV or MVA-BN-Filo. 
The safety/tolerability and immunogenicity of the Ad26.ZEBOV and MVA-BN-Filo vaccines
are 
being 
assessed 
in 
the 
ongoing 
Phase 
1 
studies
(VAC52150EBL1001 
and 
VAC52150EBL1002), where monovalent Ad26.ZEBOV and multivalent MVA-BN-Filo 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 8 weeks later. In addition, 2 other Phase 1 studies are planned to be 
conducted in Africa (VAC52150EBL1003 and VAC52150EBL1004). 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.14,15
Limited data from the ongoing Phase 1 studies with Ad26.ZEBOV and MVA-BN-Filo are 
available. 
VAC52150EBL1001, a first-in-human study, has enrolled 87 subjects for which 7-day 
post-prime safety data, blinded on a treatment group level, on 72 subjects (36 per treatment 
group) are available. Most of the adverse events reported were grade 1 or grade 2 in severity. 
Local injection site reactions were reported in 18 (50%) MVA/placebo subjects (all grade 1) and 
28 (78%) Ad26/placebo subjects (grade 1 [22], grade 2 [5], grade 3 [1]). The most frequent local 
reaction was injection site pain, in 17 (47%) MVA/placebo subjects and 28 (78%) Ad26/placebo 
subjects, with one grade 3 case occurring in the Ad26/placebo group. Solicited system ic 
reactions were reported in 25 (69%) MVA/placebo subjects (grade 1 [24] and grade 2 [1]) and 
31 (86%) Ad26/placebo subjects (grade 1 [22], grade 2 [7], grade 3 [1], unknown [1]). The most 
frequent systemic reactions were fatigue (50% overall), followed by headache (46%) and 
myalgia (35%). One Ad26/placebo subject experienced 3 grade 3 solicited systemic reactions 
(headache, myalgia and nausea). None of the subjects reported fever; however, 2 subjects had 
one temperature measurement missing. The most frequent unsolicited adverse events were 
decreased neutrophils, in 3 (8%) MVA/placebo subjects and 6 (17%) Ad26/placebo subjects, 
followed by activated partial thromboplastin time prolongation and hypokalemia, in 3 (8%) 
MVA/placebo subjects and 5 (14%) Ad26/placebo subjects each. All of these events were 
transient in nature and resolved without intervention. No deaths or serious adverse events and no 
adverse events leading to discontinuation of the study vaccination were reported. 
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 
issues have been identified to date.
Safety data generated with the 2 backbones containing different inserts are provided below.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
44
Status: Approved, Date: 4 May 2017
Safety Data From Other Ad26-based Vaccine Programs
Ad26.ZEBOV is a monovalent, replication-incompetent Ad26-based vector. Only limited clinical 
data are available for Ad26.ZEBOV. However, adenovirus vaccine programs with other gene 
inserts revealed no significant safety issues. The data described below are based on the 
evaluation of the prototype vaccine Ad26.ENVA.01, which expresses the HIV envelope gene.16
Three randomized, placebo-controlled, Phase 1 studies (IPCAVD-001, IPCAVD-003, 
IPCAVD-004) have evaluated the safety and immunogenicity of the prototype vaccine 
Ad26.ENVA.01. This prototype vaccine has been administered to more than 200 healthy, 
HIV-negative subjects between the ages of 18 and 50 years in the United States and Africa.16,17,18

In the dose-escalation study IPCAVD-001 (n=60), 2 or 3 IM doses of Ad26.ENVA.01 
(1x109, 1x1010, 5x1010, 1x1011 viral particles [vp]) were given to Ad26 seronegative 
subjects. There were no deaths or vaccine-related serious adverse events. Ad26.ENVA.01 
was generally well tolerated at all 4 dose levels with minimal reactogenicity observed in the 
1x109 and 1x1010 vp dose groups. Moderate to severe malaise, myalgia, fatigue and chills 
occurred in the majority of subjects 12 to 18 hours after the first dose of 1x1011 vp, but were 
resolved within 24 to 36 hours and were not seen after the second injection at this dose level. 
Two subjects in the 1x1011 vp dose group chose not to have the second injection, however, 
one of them decided to have the 6-month injection. Envelope-specific humoral and 
cell-mediated immune responses were induced at all 4 dose levels of vaccine.2,4

In the single-dose study IPCAVD-003 (n=24), an IM dose of Ad26.ENVA.01 (5x1010 vp) or 
placebo was given to subjects, who were stratified according to baseline Ad26 immune 
status, to evaluate the safety, mucosal immunogenicity and innate immune responses. Local 
reactogenicity comprised moderate injection site pain/tenderness and/or moderate to severe 
erythema which resolved within 3 days of vaccination. Transient systemic reactogenicity 
comprised headache, chills, joint pain, myalgia, malaise/fatigue, and fever. No deaths or 
vaccine-related serious adverse events were observed. Vaccination elicited both systemic 
and mucosal envelope-specific humoral and cellular immune responses. No increased 
activated total or vector-specific mucosal CD4+ T-lymphocytes following vaccination were 
detected in the colorectal mucosa, indicating that vaccination with Ad26 did not increase 
mucosal inflammation.1

In study IPCAVD-004 (n=217), the safety and immunogenicity of IM doses of 
Ad26.ENVA.01 and Ad35.ENV (an Ad35 vector expressing an HIV envelope GP used in 
that study at a dose of 5x1010 vp), given in heterologous and homologous prime-boost 
regimens at 3- versus 6-month intervals, was evaluated. There were 452 adverse events 
reported by 84 of 176 Ad26-vaccine recipients (47.7%), the majority being mild (75.5%) in 
severity. The proportion of subjects with moderate or severe symptoms was not statistically
significantly different between vaccine and placebo. There were 3 serious adverse events: 
2 serious adverse events in placebo recipients (grade 3 peritonsillar abscess and grade 4 
migraine headache, both resolved with no residual effects) and 1 serious adverse event in an 
Ad35/Ad26 vaccine recipient (grade 4 acute myelogenous leukemia, resolved with 
sequelae). No deaths or vaccine-related serious adverse events were reported. Overall, 97%
to
100% of
subjects developed anti-envelope binding antibodies (enzyme-linked 
immunosorbent assay [ELISA]) after a second dose, with heterologous and homologous 
regimens being comparable. Immune responses in groups who received 3- and 6-month 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
45
Status: Approved, Date: 4 May 2017
schedules were comparable. Four weeks post-vaccination, interferon (IFN)-γ enzyme-linked 
immunospot (ELISpot) assay showed response rates between 44% and 100%. The 
heterologous and homologous regimens were comparable. There was induction of 
Ad26-neutralizing antibodies in the majority of vaccine recipients after 2 immunizations 
with Ad26.ENVA.01.20
In addition, the sponsor performed a Phase 1/2a double-blind, randomized, placebo-controlled, 
dose-escalation study (MAL-V-A001) to evaluate the safety, tolerability and immunogenicity of 
2 dose levels (1x1010 and 5x1010 vp) of Ad35.CS.01/Ad26.CS.01 (both expressing the malaria 
Plasmodium falciparum circumsporozoite antigen) prime-boost regimens in healthy subjects. The 
dose-escalation phase was followed by an evaluation of efficacy of the higher dose level in an 
experimental malaria challenge. A total of 42 subjects were enrolled and were vaccinated. The 
analysis of adverse events did not show any consistent pattern suggestive of an association of 
Ad35.CS.01 or Ad26.CS.01 with specific adverse events. There were no serious adverse events 
reported during the study. No subject discontinued during a study phase (vaccination or 
challenge) due to adverse events. One subject in the high-dose group completed the vaccination 
phase and the final safety follow-up visit but did not take part in any challenge phase activities 
because of ongoing dyspnea. The most common related adverse events after each vaccination 
were injection site pain, malaise, headache, myalgia and chills. The incidence of vaccine-related 
adverse events was generally higher in the high-dose group than in the low-dose group. In 
general, incidence of malaise, headache, and myalgia were higher after the third dose (Ad26) 
than after the first or second doses (Ad35). Injection site pain was more commonly reported in 
the low and high-dose groups than by placebo subjects. There were no clinically significant 
changes in laboratory test parameters or vital signs data.6
Recent data indicate that administration of a deoxyribonucleic acid (DNA) vaccine expressing 
EBOV Mayinga GP, the same GP as in the Ad26.ZEBOV component, was safe, well tolerated 
and immunogenic in a Phase 1 clinical study. During this study, 9 subjects received three 
4-weekly IM doses of vaccine (4 mg/dose), followed by a boost at ≥32 weeks in 8 subjects.23
Based on the previous clinical experience of Ad26 vector with different inserts, there has been no 
impact of Ad26 seropositivity on subjects’ safety and only limited impact on immunogenicity 
results. Therefore, there are no safety concerns with regard to the inclusion of Ad26 seropositive 
subjects in the study, and the study subjects will not be screened for Ad26 seropositivity as part 
of the study eligibility criteria. The purpose of the Ad26 seropositivity assessment at baseline is 
to evaluate its impact, if any, on vaccine immunogenicity.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
46
Status: Approved, Date: 4 May 2017
1.1.2.2
Safety Profile of MVA-BN-based Vaccines
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.13 A Phase 3 clinical study
(POX-MVA-013) has been completed (ClinicalTrials.gov Identifier: NCT01144637).7 Results of 
completed and ongoing clinical
studies of MVA-BN-based vaccines in more than 
8,100 individuals, including elderly, children and immunocompromised subjects in whom 
replicating vaccines are contraindicated, have shown that the platform displays high 
immunogenicity and a favorable safety profile.21 Across all clinical studies, no trends for 
unexpected or serious adverse reactions due to the product were detected.
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.15
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 commonly reported local site reaction was pain at the 
injection site. All the local reactions resolved to normal without any lasting effects.
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.24,25

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
47
Status: Approved, Date: 4 May 2017
1.1.2.3
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.
1.1.2.4
Viral Shedding 
Viral shedding information is available from 6 clinical studies with Ad-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.14
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 were performed.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
48
Status: Approved, Date: 4 May 2017
1.2.
Benefit/Risk Section
Known Benefits
1.2.1.
The clinical benefit of prime-boost combinations of Ad26.ZEBOV and MVA-BN-Filo is to be 
established.
Potential Benefits
1.2.2.
Subjects may benefit from clinical testing and physical examination; others may benefit from the 
knowledge that they may aid in the development of an Ebola vaccine. There is no direct 
individual benefit from vaccination for the subjects at the current development stage.
Known Risks
1.2.3.
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 solicited local and systemic reactions, as expected with injectable 
vaccines, and no serious safety concerns in study participants. MVA-BN-based vaccines have 
been administered to more than 8,100 individuals without unexpected or serious adverse 
reactions reported. For details, see the safety data presented in Section 1.1.
Potential Risks
1.2.4.
The following potential risks for Ad26.ZEBOV and MVA-BN-Filo will be monitored during the 
study and are specified in the protocol: 
Risks Related to Vaccines
Subjects may exhibit general signs and symptoms associated with administration of a vaccine, or 
a placebo vaccination, including nausea/vomiting, headache, myalgia, arthralgia, fever, 
fatigue/malaise and chills. In addition, subjects may experience local (injection site) reactions 
such as pain/tenderness, erythema, induration/swelling and itching at the injection site. These 
events will be monitored, but are generally short-term and do not require treatment.
Subjects may have an allergic reaction to the vaccination. An allergic reaction may cause a rash, 
hives or even difficulty in breathing (anaphylaxis). Severe reactions are rare. Medications must 
be available in the clinic to treat serious allergic reactions.
The risks related to vaccine-induced seropositivity (VISP) are discussed in Section 9.5.
Risk of Myo/Pericarditis
While replicating smallpox vaccines have been associated with an increased risk to develop 
myo/pericarditis,22 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 case of pericarditis has been observed in any 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
49
Status: Approved, Date: 4 May 2017
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 
subject 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 subjects (0.8%) without evidence of myo/pericarditis.8 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.
Pregnancy and Birth Control
The effect of the study vaccines on a fetus or nursing baby is unknown, as well as the effect on 
semen, so female subjects of childbearing potential, and male subjects having sexual intercourse 
with females, are required to agree to practice adequate birth control measures for sexual 
intercourse from at least 28 days before the prime vaccination (and boost vaccination if a late 
boost vaccination will be given for subjects affected by a study pause) (or prior to enrollment for 
men) until at least 3 months after the prime vaccination or up to 1 month after the boost 
vaccination (whichever takes longer) (see Section 4.3). Women who are pregnant or breast-
feeding, or are planning to become pregnant while enrolled in the study until 3 months after the 
prime vaccination or up to 1 month after the boost vaccination (whichever takes longer), will be 
excluded from enrollment into the study. Subjects participating in the Cohort 1 substudy will be 
asked to use adequate birth control measures for sexual intercourse from at least 14 days before 
to at least 3 months after the third vaccination.
After completion of the 6-month post-last vaccination visit in the present study, subjects who 
received placebo may stop birth control measures or resume their pre-study birth control 
measures.
Risks from Blood Draws
Blood draws may cause pain/tenderness, bruising, bleeding, and, rarely, infection at the site 
where the blood is taken.
Unknown Risks
There are no clinical data on the use of either vaccine (Ad26.ZEBOV or MVA-BN-Filo) in:
Pediatric subjects (<18 years);
Pregnant or nursing women;
Adults >50 years;
Immunocompromised subjects (including those with HIV infection).
There may be other serious risks that are not known.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
50
Status: Approved, Date: 4 May 2017
Overall Benefit/Risk Assessment
1.2.5.
Based on the available data and proposed safety measures, the overall benefit/risk assessment for 
this clinical study is considered acceptable for the following reasons:
Preliminary safety data from the ongoing Phase 1 studies and safety data generated with the 
2 vaccines with different inserts revealed no significant safety issues (see Sections 1.1 and 
1.2.3). Further experience from Ad26.ZEBOV or MVA-BN-Filo will be gained from 
currently ongoing clinical studies.
Only subjects who meet all inclusion criteria and none of the exclusion criteria (specified in 
Section 4) will be allowed to participate in this study. The selection criteria include adequate 
provisions to minimize the risk and protect the well-being of subjects in the study.
Safety will be closely monitored throughout the study:

Subjects will remain at the site for a total of 60 (±15) minutes (after prime and boost 
vaccinations) or 30 (±15) minutes (after the third vaccination) post-vaccination to 
monitor the development of any acute reactions, or longer if deemed necessary by the 
investigator (eg, in case of grade 3 adverse events). Refer to Section 6.1 for more 
information on emergency care. The subjects will be closely observed by study-site 
personnel for the first 30 (±10) minutes after each vaccination, and again at 
60 (±15) minutes after prime and boost vaccinations, and any unsolicited, solicited local 
or systemic adverse events will be documented during this period. Subjects will use a 
diary to document solicited local and systemic adverse events in the evening after each 
vaccination and then daily for the next 7 days at approximately the same time each day. 
Diaries should be completed at home by the subject (or parent, legal guardian or 
caregiver, as applicable). For illiterate subjects or those having difficulty completing the 
diary independently, the sites will make arrangements to have the diary completed 
according to their local practice.
The investigator or the designee will document unsolicited adverse events from signing of 
the informed consent form (ICF)/assent onwards until 42 days post-last vaccination
(excluding the third vaccination), and again from the day of the third vaccination until 
28 days thereafter for subjects in the Cohort 1 substudy (note: events that started before the 
third vaccination but are still present at the time of third vaccination should also be 
recorded). The investigator or the designee will document serious adverse events and 
immediate reportable events (IREs) from signing of the ICF/assent onwards until the end 
of the study.
Safety measures, including an electrocardiogram (ECG; for subjects ≥18 years, performed 
at screening), physical examinations, vital sign measurements, clinical laboratory and 
pregnancy testing, will be performed at scheduled visits during the study, which lasts up to 
1 year after the prime vaccination in subjects who received Ad26.ZEBOV or MVA-BN-
Filo. 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
51
Status: Approved, Date: 4 May 2017
Any clinically significant abnormalities (including those persisting at the end of the 
study/early withdrawal) will be followed by the investigator until resolution or until a 
clinically stable endpoint is reached.
Several safety measures are included in this protocol to minimize the potential risk to subjects, 
including the following:
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.
There are pre-specified pausing rules that would result in pausing of further vaccination if 
predefined conditions occur, preventing exposure of new subjects to study vaccine until an 
Independent Data Monitoring Committee (IDMC) reviews all safety data
(see
Section 9.3.2).
Subjects will discontinue study vaccine for the reasons included in Section 10.2.
If acute illness (excluding minor illnesses such as diarrhea or mild upper respiratory tract 
infection) or fever (body temperature ≥38.0 °C) occur at the scheduled time for 
vaccination, the subject may be vaccinated up to 10 days beyond the window allowed for 
the scheduled vaccination, or be withdrawn from that vaccination at the discretion of the 
investigator and after consultation with the sponsor (see Section 6.2).
Contraindications to boost and third vaccinations are included in Section 6.3.
If a subject withdraws from the study (withdrawal of consent), he/she maintains the option 
to participate in the safety follow-up (see Section 10.2).
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). Further nonclinical studies are ongoing to evaluate the 
protection of the multivalent vaccine regimen in additional animals and to assess the protective 
efficacy of a combination regimen of Ad26.ZEBOV and MVA-BN-Filo (either a simultaneous 
administration or as prime-boost regimen). 
In humans, both Ad26- and MVA-based vaccines containing various antigenic inserts have been 
shown to be safe and immunogenic (see Section 1.1). To date, more than 230 subjects have 
received the sponsor’s Ad26-based vaccines in completed clinical studies (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.21 Although routinely used by the subcutaneous route, MVA-BN at a 
dose of 1x108 50% Tissue Culture Infective Dose (TCID50) has been demonstrated to be as safe 
and immunogenic when used by the IM route.10,26 The IM route has been chosen for the present 
study. 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
52
Status: Approved, Date: 4 May 2017
The unprecedented size and scale of the ongoing Ebola disease outbreak that started in 
December 2013 in Guinea and subsequently spread to Sierra Leone, Nigeria 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 Ebola disease. It will 
test schedules that are being evaluated in ongoing NHP challenge and Phase 1 clinical studies. 
In this Phase 2 study, the sponsor’s Ad26 vector expressing the EBOV Mayinga GP 
(Ad26.ZEBOV) and the MVA-BN vector with EBOV, SUDV and MARV GP inserts and TAFV 
NP insert (MVA-BN-Filo) will be evaluated as a heterologous 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 28, 56 or 84 days 
later. At selected sites in Cohort 1 (Groups 1 and 2), a third vaccination (Ad26.ZEBOV) will be 
given at least 1 year post prime (substudy). The EBOV GP that is currently circulating in West 
Africa has 97% homology to the EBOV GP used in this vaccine regimen.3 The concept of a 
prime-boost regimen that will be evaluated in the Phase 2 studies with the candidate prophylactic 
Ebola vaccines Ad26.ZEBOV and MVA-BN-Filo is supported by the results of clinical studies 
with candidate malaria vaccines which have demonstrated that Ad-based prime immunization 
followed by MVA-vector boost induced high levels of immunity.
For the prevention of Ebola virus disease, short vaccination schedules may be relevant in the 
context of the epidemic and suitable for use during acute outbreaks of Ebola. When the current 
outbreak is under control, longer vaccination schedules may be more relevant than the shorter 
prime-boost intervals provided a more persistent immune response is observed. The 14-, 28- and 
56-day prime-boost intervals are being evaluated in the current Phase 1 studies. An interval 
longer than 56 days may provide better protection than shorter schedules. Therefore, the 
objective of this study is to evaluate the immunogenicity of intervals that are slightly shorter as 
well as slightly longer relative to the 56-day schedule (ie, the schedule that yielded 100% 
protection in NHP).
The 3 different time intervals (of 28, 56 or 84 days) between the prime and the boost vaccination 
will be evaluated for safety and tolerability as well as for immunogenicity. These 3 prime-boost 
regimens will differ only in the timing of the boost vaccination, while the dose of each vaccine 
and the sequence of vaccination will be identical. The prime vaccine consists of Ad26.ZEBOV at 
a dose of 5x1010 vp and the boost vaccine consists of MVA-BN-Filo at a dose of 1x108 infectious 
units (Inf U, nominal titer). The MVA-BN-Filo dose to be used corresponds to the dose of 
1x108 TCID50 that is used in the current Phase 1 studies. In the Cohort 1 substudy, the third 
vaccination consists of Ad26.ZEBOV at a dose of 5x1010 vp.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
53
Status: Approved, Date: 4 May 2017
This Phase 2 study will be conducted to enlarge the safety and immunogenicity database for the 
Ad26.ZEBOV and MVA-BN-Filo prime-boost regimens and to extend the population studied in 
Phase 1 to include elderly subjects (>50 to 70 years inclusive), HIV-infected subjects, and 
healthy children (in 2 age strata) in order to cover a large spectrum of the population that would 
receive a vaccine in a future outbreak setting (ie, mass or ring vaccination). In this Phase 2 study, 
healthy adult subjects will also be included, ie, the population studied in the Phase 1 studies and 
in the Phase 2 study performed in Europe (VAC52150EBL2001). In addition, administration of a 
third vaccination with Ad26.ZEBOV in the Cohort 1 substudy will extend the findings to an 
African population and confirm the immunogenicity profile from a Phase 1 study (see 
Section 3.2).
2.
OBJECTIVES AND HYPOTHESIS
2.1.
Objectives
Primary Objective
The primary objective is to assess the safety and tolerability of different vaccination schedules of 
Ad26.ZEBOV and MVA-BN-Filo administered IM as heterologous prime-boost regimens on 
Days 1 and 29, Days 1 and 57, or Days 1 and 85, in healthy adults, including elderly subjects, 
and on Days 1 and 29 and Days 1 and 57 in HIV-infected subjects and healthy children in 2 age 
strata.
Secondary Objectives
The secondary objectives are:

To assess humoral immune responses, as measured by ELISA, to the EBOV GP at 21 days 
post boost of different vaccination schedules of Ad26.ZEBOV and MVA-BN-Filo
administered IM as heterologous prime-boost regimens on Days 1 and 29, Days 1 and 57, or 
Days 1 and 85, in healthy adults, including elderly subjects, and on Days 1 and 29 and
Days 1 and 57 in HIV-infected subjects and healthy children in 2 age strata.

To assess the safety and tolerability of a third vaccination with Ad26.ZEBOV administered 
at least 1 year post prime in a subset of approximately 90 healthy adults, including elderly 
subjects, in Cohort 1 (Groups 1 and 2).
Exploratory Objectives
The exploratory objectives are:

To assess humoral immune responses, as measured by ELISA, to the EBOV GP at other 
relevant time points of different vaccination schedules of Ad26.ZEBOV and MVA-BN-Filo 
administered IM as heterologous prime-boost regimens on Days 1 and 29, Days 1 and 57, or 
Days 1 and 85, in healthy adults, including elderly subjects, and on Days 1 and 29 and 
Days 1 and 57 in HIV-infected subjects and healthy children in 2 age strata. 

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
To assess the neutralizing capacity of the EBOV GP-specific humoral immune responses, as
measured by virus neutralization assay, to the EBOV GP of different vaccination schedules 
of Ad26.ZEBOV and MVA-BN-Filo administered IM as heterologous prime-boost 
regimens on Days 1 and 29, Days 1 and 57, or Days 1 and 85, in healthy adults, including 
elderly subjects, and on Days 1 and 29 and Days 1 and 57 in HIV-infected subjects and 
healthy children in 2 age strata.

To explore humoral and cellular immune responses to different EBOV GPs and the 
adenovirus and/or MVA backbone of the various vaccination schedules tested. 

To explore humoral and cellular immune responses to filovirus GPs and/or TAFV NP, if 
assays are available.

To assess humoral immune responses, as measured by ELISA, to the EBOV GP at various 
time points following a third vaccination with Ad26.ZEBOV at least 1 year post prime in 
approximately 90 healthy adults, including elderly subjects, in Cohort 1 (Groups 1 and 2).
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 randomized, observer-blind, placebo-controlled, parallel-group, multicenter, Phase 2 
study in Africa to evaluate the safety, tolerability and immunogenicity of different heterologous 
prime-boost regimens using Ad26.ZEBOV at a dose of 5x1010 vp as prime and MVA-BN-Filo at 
a dose of 1x108 Inf U (nominal titer) as boost at a 28-, 56- or 84-day interval in healthy adult and 
elderly subjects. The same prime-boost schedules, except for the 84-day interval, will be 
evaluated in HIV-infected subjects and healthy children in 2 age strata. At selected sites in 
Cohort 1 (Groups 1 and 2), a third vaccination with Ad26.ZEBOV will be administered at least 
1 year post prime to subjects who consent to this (Cohort 1 substudy). Subjects who received a 
late boost vaccination or did not receive the boost vaccination at all due to a study pause will not 
be included in the Cohort 1 substudy. 
This study will enroll a planned total number of 1,056 subjects, who have never received a 
candidate Ebola vaccine and have no prior exposure to Ebola virus (including travel to epidemic 
Ebola areas less than 1 month prior to screening) or a diagnosis of Ebola virus disease.
The study is comprised of 3 cohorts, which will be enrolled sequentially (see Figure 1): healthy 
adult and elderly subjects (aged 18 to 70 years inclusive, Cohort 1), HIV-infected subjects (aged 
18 to 50 years inclusive, Cohort 2a) and healthy children in 2 age strata (adolescents aged 12 to 
17 years inclusive, Cohort 2b; children aged 4 to 11 years inclusive, Cohort 3). The prime-boost 
regimens that will be evaluated in this study will differ only in the timing of the boost 
vaccination (ie, 28, 56 or 84 days after prime, respectively referred to as Groups 1, 2 and 3), 
while the dose of each study vaccine (Ad26.ZEBOV, MVA-BN-Filo or placebo) and the 

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sequence of prime-boost vaccination will be identical. Groups 1 and 2 will be evaluated in each 
cohort, while Group 3 (84-day interval) will be evaluated in Cohort 1 only. 
In Cohort 1, subjects will be enrolled in parallel and randomized in a 1:1:1 ratio to Groups 1, 
2 and 3 at baseline until a target of 132 subjects have been included in Group 3. Afterwards, 
randomization in this cohort will proceed in a 1:1 ratio to Groups 1 and 2. In Cohorts 2a, 2b, 
and 3, subjects will be enrolled in parallel and randomized in a 1:1 ratio to Groups 1 and 2 at 
baseline. Within each group (for all cohorts), subjects will be randomized in a 5:1 ratio to receive 
Ad26.ZEBOV and MVA-BN-Filo versus placebo.
Available interim analysis results of 7-day post-prime safety and immunogenicity data from the 
ongoing and/or planned Phase 1 studies (studies in Europe, US and Africa) will be provided
before the start of the present study, which will start with Cohort 1. Progression to the next 
cohort will proceed following favorable IDMC review:

Cohorts 2a and 2b can start when 25% of subjects in Cohort 1 have completed their 7-day 
post-prime visit.

Cohort 3 can start when 50% of subjects in Cohort 2b have completed their 7-day 
post-prime visit.
The real-time monitoring of blinded data will be conducted by the sponsor. The interim data 
(unblinded) will be provided to and reviewed by the IDMC. The decision to open Cohorts 2a, 2b,
and 3 will be based on the sponsor’s and the IDMC’s review of the interim safety data. 
Progression to the next cohort will also take into account pre-specified pausing rules (see 
Section 9.3.2). 

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A schematic overview of the study design is presented in Figure 1.
Figure 1:
Schematic Overview of the Study 
Group 1:
Day 1, Day 29
Group 2:
Day 1, Day 57
Group 3:
Day 1, Day 85 
(in Cohort 1 
only)
Cohort 1
Cohort 1 Substudy (Day 365)
Healthy adult and elderly subjects (220/44 in Group 1, 
220/44 in Group 2 and 110/22 in Group 3)
Healthy adult and elderly subjects 
(total of 90* in Groups 1 and 2)
Cohort 2a
HIV-infected subjects 
(55/11 in Groups 1 and 2)
Cohort 2b
Adolescents (12-17 years incl.) 
(55/11 in Groups 1 and 2)
Cohort 3
Children (4-11 years incl.) 
(55/11 in Groups 1 and 2)
Number/number: number of subjects per group randomized to Ad26.ZEBOV and MVA-BN-Filo/placebo.

Cohorts 2a and 2b: starts when 25% of subjects from Cohort 1 have reached the 7-day post-prime visit

Cohort 3: starts when 50% of subjects from Cohort 2b have reached the 7-day post-prime visit
*
Subjects who received Ad26.ZEBOV and MVA-BN-Filo will receive Ad26.ZEBOV as third vaccination at 
least 1 year post prime. Subjects who received placebo will receive placebo as third vaccination at least 1 year 
post prime.
Within each cohort, study-site personnel (except for those with primary responsibility for study 
vaccine preparation and dispensing), and subjects will be blinded to the study vaccine allocation 
until the last subject in that cohort has completed the study. Refer to Section 5 for further details 
on blinding in case of interim analyses.
The study consists of a screening phase of up to 8 weeks (starting from the moment the subject 
signs the ICF and/or informed assent), a vaccination phase in which subjects will be vaccinated 
at baseline (Day 1) followed by a boost vaccination on Day 29, 57 or 85, and a post-vaccination 
phase and long-term follow-up phase until Day 365. The Cohort 1 substudy consists of a 
vaccination phase in which subjects will be vaccinated at least 1 year post prime vaccination, a 
post-vaccination phase, and a long-term follow-up phase until the 1-year post third vaccination 
visit. All subjects within a cohort will be followed in a blinded manner by the site until the last 
subject in that cohort has completed the study. Any subject who completed either the 6-month 
post-prime and/or the Day 365 visit prior to approval of Amendment 2 was required to attend the 
6-month post-boost and the Day 365 visit after approval of Amendment 2. Refer to Section 9.1.6
for study procedures that need to be followed in case of a study pause.
The baseline visit may be scheduled as soon as the results of all screening assessments are 
known (but should occur within 8 weeks from screening, see Section 9.1.2) and show that the 
subject is eligible for inclusion. The administration of the prime vaccination will occur on Day 1 
(baseline), after the completion of all baseline assessments. 

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All subjects will receive the study vaccine (Ad26.ZEBOV, MVA-BN-Filo or placebo) through 
IM injection (0.5 mL) in the deltoid muscle: 
Ad26.ZEBOV (5x1010 vp) on Day 1, followed by a boost vaccination of MVA-BN-Filo 
(1x108 Inf U) on Day 29, 57 or 85; OR
Placebo (0.9% saline) on Day 1, followed by a boost vaccination of placebo (0.9% saline) on 
Day 29, 57 or 85.
In a substudy at selected sites, approximately 90 healthy adult subjects in Cohort 1 (Groups 1 
and 2) will receive a third vaccination with Ad26.ZEBOV at 5x1010 vp or placebo at least 1 year 
post prime vaccination.
Refer to Section 6 for further details on dosage and administration. Subjects will remain at the 
site for a total of 60 (±15) minutes (after prime and boost vaccinations) or 30 (±15) minutes
(after the third vaccination) post-vaccination to monitor for the development of any acute 
reactions, or longer if deemed necessary by the investigator (eg, in case of grade 3 adverse 
events). 
The investigators, together with the sponsor’s medical monitor, will be responsible for the safety 
monitoring of the study, and will halt vaccination of further subjects in case any of the 
pre-specified pausing rules described in Section 9.3.2 have been met. Criteria for postponement 
of vaccination at the scheduled time for vaccine administration and contraindications to boost
and third vaccinations have been defined and will be applied by the investigator (not including 
those occurring because of study hold) (see Sections 6.2 and 6.3 respectively). Discontinuation 
of study vaccine should occur in any subject meeting the criteria outlined in Section 10.2.
Safety will be assessed by collection of solicited local and systemic adverse events 
(reactogenicity), unsolicited adverse events, serious adverse events, and IREs. The subjects will 
be closely observed by study-site personnel for the first 30 (±10) minutes after each vaccination,
and again at 60 (±15) minutes after prime and boost vaccinations, and any unsolicited, solicited 
local or systemic adverse events will be documented during this period. Upon discharge from the 
site, subjects will receive a diary, a thermometer and a ruler to measure solicited local reactions 
and body temperature. Subjects will be instructed to record solicited local and systemic adverse 
events in the diary in the evening after each vaccination and then daily for the next 7 days at 
approximately the same time each day. Diaries should be completed at home by the subject (or 
parent, legal guardian or caregiver, as applicable). For illiterate subjects or those having 
difficulty completing the diary independently, the sites will make arrangements to have the diary 
completed according to their local practice. The investigator will document unsolicited adverse 
events from signing of the ICF/assent onwards until 42 days post-last vaccination (excluding the 
third vaccination), and again from the day of the third vaccination until 28 days thereafter for 
subjects in the Cohort 1 substudy (note: events that started before the third vaccination but are 
still present at the time of third vaccination should also be recorded). The investigator will 
document serious adverse events and IREs from signing of the ICF/assent onwards until the end 
of the study. The primary (or secondary for Cohort 1 substudy) endpoints are adverse events, 

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serious adverse events, IREs and solicited local and systemic adverse events (see Section 11.1). 
Other safety assessments include an ECG for subjects ≥18 years of age (performed at screening), 
physical examination, vital signs (blood pressure, pulse/heart rate, body temperature), clinical 
laboratory and pregnancy testing. 
In addition, the investigator will collect samples for immunogenicity assessments at the time 
points indicated in the Time and Events Schedule. Samples to assess humoral responses will be 
taken from all subjects; samples to assess cellular immune responses will be taken from subjects 
at selected sites (targeted at 165 subjects [138 Ad26.ZEBOV and MVA-BN-Filo, and 
27 placebo] in Cohort 1 and 33 subjects [28 Ad26.ZEBOV and MVA-BN-Filo, and 5 placebo] in 
each of the other cohorts). Peripheral blood mononuclear cell (PBMC) sampling at selected sites 
will continue until the targeted number of subjects is reached. Samples to assess cellular immune 
responses are optional for subjects in the Cohort 1 substudy and may only be collected in a 
subset of subjects. Subjects giving informed consent for the study will be informed that their 
leftover blood samples will be stored for potential future research. Subjects participating at 
selected sites where PBMC samples are collected will be asked explicitly to consent for potential 
future genetic research to be performed on PBMC samples. Subjects can withdraw consent for 
their samples to be used for future research at any time (see Section 16.2.5).
The primary analysis will be conducted when all subjects in Cohort 1 have completed the 
6-month post-boost visit or discontinued earlier, to aid in the assessment of which vaccination 
schedule will be the best candidate for future studies and implementation in the field. Study-site 
personnel, subjects and sponsor personnel involved in subject level data review will remain 
blinded until the last subject in that cohort has completed the study. Sponsor personnel involved 
in the conduct of the primary analysis and in making future decisions for the program will be 
unblinded to the data of Cohort 1, but will remain blinded to the data of the other cohorts.
For the Cohort 1 substudy of subjects who received the third vaccination, an interim analysis 
may be performed when all subjects have completed the 6-month post third vaccination visit, or 
discontinued earlier.
In each cohort, after completion of the 6-month post-boost visit by all subjects, an interim
analysis will be conducted on safety and selected immunogenicity data and the cohort will be 
unblinded to the sponsor. Subjects who completed the 6-month post-prime visit prior to approval 
of Amendment 2 were required to attend the 6-month post-boost visit after approval of 
Amendment 2.  
The final analysis will be performed when all subjects have completed the last study-related visit 
or discontinued earlier (including subjects participating in the Cohort 1 substudy).
While Cohort 1 was enrolling, the sponsor halted all vaccinations in this study due to the 
occurrence of a serious and very rare condition, Miller Fisher syndrome, reported in study 
VAC52150EBL2001 (described in Section 1.1.2.3) until a revised ICF was prepared and 
approval to restart the study was granted by the relevant competent authority. This interruption in 
dosing affected over 200 consented subjects, some who were awaiting prime vaccination and 

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some awaiting boost vaccination. When approval was granted to restart the study under 
Amendment 1, a late boost vaccination has been offered to those subjects who were out-of-
window for the boost vaccination, unless it was prohibited. Those subjects who agreed to the late 
boost have been following the procedures as outlined in Amendment 1. 
All subjects (including placebo) who were primed prior to the pause and did not/will not receive 
a late boost vaccination are being followed every 3 months after the prime vaccination for safety 
until Day 365 (see Additional Time and Events Schedule for subjects who do not receive a boost 
vaccination because of a study pause). Therefore, non-serious adverse events will be reported 
until the 42-day post-last vaccination (excluding third vaccination) visit rather than the 42-day
post-boost vaccination visit. Serious adverse events and IREs will be reported throughout the 
study until Day 365 (for details, see Section 9.3.1). 
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 placebo) 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 placebo) (unless local 
regulations have additional requirements for follow-up) will be eligible for enrollment into the 
VAC52150 Vaccine Development Roll-over study (VAC52150EBL4001) for long-term 
surveillance (for a total of up to 60 months after the prime vaccination) (see Section 9.1.8 for 
details). After unblinding, only female subjects and the children of female subjects who received 
Ad26.ZEBOV and/or MVA-BN-Filo will remain in the VAC52150 Vaccine Development Roll-
over study for long-term surveillance. After unblinding, female subjects and the children of
female subjects who received placebo and have already been enrolled into the VAC52150 
Vaccine Development Roll-over study will be discontinued from further participation in the roll-
over study.
3.2.
Study Design Rationale
The study design is largely driven by the accelerated development approach of the Ad26.ZEBOV 
and MVA-BN-Filo prime-boost combination. Based on the growing availability of data from the 
entire development program as the study proceeds, modifications to the study design may be 
considered. For instance, if the results from the 28-day prime-boost interval (or any other 
interval) are not favorable based on the evaluation of the NHP and Phase 1 data (safety and 
immunogenicity) as soon as these become available, the enrollment in this group will be stopped 
(if not yet completed). When enrollment in one of the regimens will be stopped, the number of 
subjects still to be enrolled for this regimen will be randomized to the other regimen(s) to ensure 
that the same number of subjects can be included in an overall safety database of the 
Ad26.ZEBOV and MVA-BN-Filo prime-boost regimen.
The interruption in dosing and subsequent restart has required changes to the management of the 
subjects affected by the pause. All subjects (including placebo) who were primed prior to the 
pause and did not/will not receive a late boost vaccination will be followed for safety. Subjects 

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who did/will receive a late boost vaccination will follow the same post-boost vaccination 
schedule as those subjects unaffected by the pause (for details, see Section 9.1.6).
Immunogenicity data from a Phase 1 study (VAC52150EBL1002) demonstrated stability of the 
binding antibody 
response 
out 
to 
1 
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 1-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 
strongly suggests that robust anamnestic responses can be induced after re-exposure to an EBOV 
antigen, in this case mimicked by a third vaccination. Administration of a third vaccination with
Ad26.ZEBOV at least 1 year post prime for approximately 90 subjects in Cohort 1 will extend 
the findings to an African population and confirm the immunogenicity profile from the Phase 1 
study.
Control and Blinding
Randomization will be used to minimize bias in the assignment of subjects to vaccination 
schedules (groups), to increase the likelihood that known and unknown subject attributes 
(eg, demographic and baseline characteristics) are evenly balanced across groups, and to enhance 
the validity of possible statistical comparisons across groups.
In addition, randomization will be used to minimize bias in the assignment of subjects to study 
vaccine (Ad26.ZEBOV and MVA-BN-Filo versus placebo). Placebo recipients are included for 
blinding purposes and safety analyses, and will provide control specimens for immunogenicity 
assays. For the purposes of regulatory submission, a placebo control will be used up to 6 months
post-boost to establish the frequency and magnitude of changes in clinical and immunologic 
endpoints that may occur in the absence of Ad26.ZEBOV or MVA-BN-Filo. The nature of the 
study vaccine (Ad26.ZEBOV and MVA-BN-Filo versus placebo) will be blind 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 procedure, and by the administration of vaccine in a masked 
syringe by a blinded vaccine administrator (see Definitions of Terms). No additional placebo 
injections will be administered to mask the vaccination schedule across groups.
Study Groups
The 3 vaccination schedules (Groups 1, 2, and 3) will only differ in the timing of the boost 
vaccination (ie, 28-, 56-, or 84-day interval), while the dose of each vaccine and the sequence of 
vaccination will be identical. The prime vaccine consists of Ad26.ZEBOV at a dose of 5x1010 vp 
and the boost vaccine consists of MVA-BN-Filo at a dose of 1x108 Inf U, which corresponds to 
the dose of 1x108 TCID50 that is used in the current Phase 1 studies. The safety, tolerability and 
immunogenicity results for the 3 vaccination schedules will be evaluated in the study. The 
84-day interval may be evaluated in the special populations at a later point in time of the 
development program. The safety, tolerability and immunogenicity results of a third vaccination

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with Ad26.ZEBOV at a dose of 5x1010 vp (at least 1 year post prime vaccination) will be 
evaluated in the Cohort 1 substudy. 
Future Research
Subjects giving informed consent for the study will be informed that their leftover blood samples 
(serum and/or PBMC) will be stored for potential future research (see Section 16.2.5). Future 
scientific research may be conducted to further investigate Ebola vaccine- and disease-related 
questions. This may include the development of new or the improvement of existing techniques 
to characterize EBOV-directed immune responses or diagnostic tests. Subjects participating at 
selected sites where PBMC samples are collected will be asked explicitly to consent for potential 
future genetic research to be performed on PBMC samples. Subjects can withdraw consent for 
their samples to be used for future research at any time.
4.
SUBJECT POPULATION
Screening of subjects for eligibility will be performed within 8 weeks before administration of 
study vaccine on Day 1. Subjects (or parent[s]/legal guardian for pediatric subjects less than 
18 years of age) 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. Assent should be 
obtained from children capable of understanding the nature of the study, typically subjects 
7 years of age and older, depending on local regulations and practice (see also Sections 1.1 and
16.2.3). Signing of the ICF and/or informed assent needs to be done before the first study-related 
activity.
The inclusion and exclusion criteria for enrolling subjects in this study are described in the 
following 2 subsections. If there is a question about the inclusion or exclusion criteria below, the 
investigator must consult with the appropriate sponsor representative and resolve any issues 
before enrolling a subject in the study. Waivers are not allowed.
For a discussion of the statistical considerations of subject selection, refer to Section 11.2, 
Sample Size Determination.
NOTE: The investigator 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 any available laboratory 
results or the receipt of additional medical records) after screening but before Day 1 so the 
subject no longer meets the eligibility criteria, then the subject should be excluded from further 
participation in the study. Section 17.4 describes the required documentation to support meeting 
the enrollment criteria.

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4.1.
Inclusion Criteria 
Inclusion Criteria for Healthy Adult and Elderly Subjects
4.1.1.
Each potential subject must satisfy all of the following criteria to be enrolled in the study.
1. 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 with the conduct of the study.
2. Subject must be a man or woman aged 18 (or the legal age of consent in the jurisdiction 
in which the study is taking place) to 70 years of age, inclusive at randomization.
3. Subject must be healthy in the investigator’s clinical judgment on the basis of medical 
history, ECG, physical examination and vital signs performed at screening.
4. Criterion modified per Amendment 2
4.1.
Subject must be healthy on the basis of 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. However, the 
subject should not be included when hemoglobin is lower than the institutional normal 
reference range (or below the values in Attachment 4 when that range is not available).
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: In case of menstruation, urinalysis must be postponed but a result should be 
available before the prime vaccination. All urinalyses should be collected as freshly 
voided, mid-stream, clean catch samples obtained after proper cleansing.
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.

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5. Criterion modified per Amendment 2
5.1.
Before randomization (on Day 1), a sexually active woman must be either:

Of childbearing potential and practicing a highly effective method of birth control 
consistent with local regulations regarding the use of birth control methods for 
subjects participating in clinical studies, beginning at least 28 days prior to 
vaccination. The sponsor considers the following methods of birth control to be 
highly effective: established use of oral, injected or implanted hormonal methods of 
contraception; placement of an intrauterine device or intrauterine system; barrier 
methods (condom or occlusive cap [diaphragm or cervical/vault caps] with 
spermicidal foam/gel/film/cream/suppository); male partner sterilization (the 
vasectomized partner should be the sole partner for that subject). More restrictive 
measures may be required by the site. 
Note: Abstinence or natural family planning are not acceptable birth control methods. 
OR

Not of childbearing potential: postmenopausal (>45 years of age with amenorrhea for 
at least 2 years or ≤45 years of age with amenorrhea for at least 6 months and a 
serum follicle stimulating hormone (FSH) level >40 mIU/mL); permanently 
sterilized (eg, bilateral tubal occlusion [which includes tubal ligation procedures as 
consistent with local regulations], hysterectomy, bilateral salpingectomy, bilateral 
oophorectomy); or otherwise be incapable of pregnancy. 
Note: If the social situation of a woman changes after start of the study (eg, woman who 
is not heterosexually active becomes active), she must begin a highly effective method of 
birth control, as described above.
Note: Women ≤45 years of age with amenorrhea for ≤6 months are considered of 
childbearing potential and do not need FSH testing.
6. A woman of childbearing potential must have a negative serum β-human chorionic 
gonadotropin -hCG) pregnancy test at screening and a negative urine -hCG pregnancy 
test immediately prior to each study vaccine administration.
Note: If the pregnancy test result is positive, in order to maintain subject confidentiality, 
the investigator will ensure adequate counseling and follow-up will be made available
particularly for adolescent subjects.
7. Criterion modified per Amendment 2
7.1.
A man who is sexually active with a woman of childbearing potential must be willing 
to use condoms for sexual intercourse beginning prior to enrollment, unless a vasectomy 
was performed more than 1 year prior to screening.
8. Subject must be available and willing to participate for the duration of the study visits and 
follow-up.
9. Subject must be willing and able to comply with the protocol requirements, including the 
Prohibitions and Restrictions specified in Section 4.3.
10. Subject must be willing to provide verifiable identification.

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11. Subject must have a means to be contacted.
12. Criterion modified per Amendment 2
12.1. Subject must pass the test of understanding (TOU) (Attachment 1).
Note: If subjects fail the TOU test on the first attempt, subjects must be retrained on the 
purpose of the study and must take the test again (2 repeats are allowed). If subjects fail 
on the third attempt, they should not continue with screening or consenting procedures.
Additional Inclusion Criteria for HIV-infected Subjects
4.1.2.
All of the inclusion criteria for healthy adult and elderly subjects (see Section 4.1.1) must be met 
by adults who are HIV-infected with the following additions/clarifications:
13. Subject must be a man or woman aged 18 (or the legal age of consent in the jurisdiction 
in which the study is taking place) to 50 years of age, inclusive at randomization.
14. Subject must have a documented HIV-infection for at least 6 months prior to screening.
15. Criterion modified per Amendment 3
15.1. Subject must be on a stable regimen of Highly Active Antiretroviral Therapy
(HAART), taking into account the following criteria:
a.
HAART is defined as potent anti-HIV treatment including a combination of 
≥3 antiretroviral agents (ARVs; low-dose ritonavir does not count as an ARV) 
whose purpose is to reduce viral load to undetectable levels. Mono- or bitherapy 
will not be allowed.
b. HAART is considered stable if subjects did not change their ARVs within the last 
4 consecutive weeks prior to start of screening. Changes in formulations are 
allowed.
c.
A subject entering the study on HAART should have a screening CD4+ cell count 
>350 cells/L. Two documented results from at least 4 weeks apart are preferred.
Viral load assessments may be used to establish effectiveness of viral suppression.
d. Subject must be willing to continue their HAART throughout the study as 
directed by their local physician.
16. Subject must be in an otherwise reasonably good medical condition (absence of acquired 
immunodeficiency syndrome [AIDS]-defining illnesses or clinically significant disease), 
diagnosed on the basis of physical examination, medical history and the investigator’s 
clinical judgment (refer to Section 4.1.1 for details).

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Inclusion Criteria for Pediatric Subjects 
4.1.3.
Each potential subject must satisfy all of the following criteria to be enrolled in the study:
17. Parent(s)/legal guardian must have signed an ICF indicating that they understand the 
purpose of, and procedures required for, the study, are willing/able to adhere to the 
prohibitions and restrictions specified in the protocol and study procedures, and are 
willing for their child to participate in the study. Informed assent must be obtained from 
adolescents and older children, depending on local regulations and practice (see also 
Section 4).
Note: Consent from both parents might be required according to local regulations and 
practice.
18. Criterion modified per Amendment 3
18.1. Criterion modified per Amendment 2
18.2. Subject must be male or female whose age on the day of randomization is within one 
of the 2 age strata in the study: 12-17 years or 4-11 years (all ages inclusive).
19. Subject must be healthy in the investigator’s clinical judgment (and the parent(s)/legal 
guardian) on the basis of medical history, physical examination and vital signs performed 
at screening.
20. Criterion modified per Amendment 2
20.1. Subject must be healthy on the basis of 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. However, the 
subject should not be included when hemoglobin is lower than the institutional normal 
reference range (or below the values in Attachment 4 when that range is not available).
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: In case of menstruation, urinalysis must be postponed but a result should be 
available before the prime vaccination. All urinalyses should be collected as freshly 
voided, mid-stream, clean catch samples obtained after proper cleansing.
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.

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21. Criterion modified per Amendment 2
21.1. Before randomization (on Day 1), a female subject must be either:
-
Of childbearing potential and practicing a highly effective method of birth control 
consistent with local regulations regarding the use of birth control methods for 
subjects participating in clinical studies, beginning at least 28 days prior to 
vaccination. The sponsor considers the following methods of birth control to be 
highly effective: established use of oral, injected or implanted hormonal methods of 
contraception; placement of an intrauterine device or intrauterine system; barrier 
methods (condom or occlusive cap [diaphragm or cervical/vault caps] with 
spermicidal foam/gel/film/cream/suppository); male partner sterilization (the 
vasectomized partner should be the sole partner for that subject). More restrictive 
measures may be required by the site.
Note: Abstinence or natural family planning are not acceptable birth control methods for 
sexually active women of any age. 
OR
-
Not of childbearing potential: premenarchal.
Note: If the social situation of a female subject changes after start of the study (eg, female 
subject who is not heterosexually active becomes active), she must begin a highly 
effective method of birth control, as described above.
22. A female subject of childbearing potential must have a negative serum β-hCG pregnancy 
test at screening and a negative urine β-hCG pregnancy test immediately prior to each 
study vaccine administration.
Note: If the pregnancy test result is positive, in order to maintain subject confidentiality, 
the investigator will ensure adequate counseling and follow-up will be made available.
23. Criterion modified per Amendment 2
23.1. A male subject who is sexually active with a female subject of childbearing potential 
must be willing to use condoms for sexual intercourse beginning prior to enrollment.
24. Subject and parent(s)/legal guardian are available and willing to participate for the 
duration of the study visits and follow-up.
25. Subject and parent(s)/legal guardian must be willing and able to comply with the protocol 
requirements, including the Prohibitions and Restrictions specified in Section 4.3.
26. Subject and parent(s)/legal guardian must have a means to be contacted.

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27. Criterion modified per Amendment 2
27.1. The parent(s)/legal guardian must pass the TOU (Attachment 1). Older children and 
adolescents who provided assent according to local regulations and practice, must also 
pass the TOU.
Note: If the subject/parent(s)/legal guardian fails the TOU test on the first attempt, he/she 
must be retrained on the purpose of the study and must take the test again (2 repeats are 
allowed). If subjects fail on the third attempt, they should not continue with screening or 
consenting procedures.
28. Subject has received all routine immunizations appropriate for his or her age as reported 
by the parent(s)/legal guardian, according to local routine vaccination schedules. Subjects 
are allowed to catch up on routine immunizations if needed (support for beneficial 
vaccines may be offered to participants).
4.2.
Exclusion Criteria 
Exclusion Criteria for Healthy Adult and Elderly Subjects
4.2.1.
Any potential subject who meets any of the following criteria will be excluded from participating 
in the study. 
1. Has received any candidate Ebola vaccine.
2. Diagnosed with Ebola virus disease, or prior exposure to Ebola virus, including travel to 
epidemic Ebola areas less than 1 month prior to screening. 
Note: Participation of international volunteers to Ebola operations is allowed, but they 
should comply with the prohibitions and restrictions as specified in Section 4.3.
3. Has received any experimental candidate Ad26- or MVA-based vaccine in the past.
Note: Receipt of any approved vaccinia/smallpox vaccine or Ad-based candidate vaccine 
other than Ad26 at any time prior to study entry is allowed.
4. Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or 
vaccine products (including any of the constituents of the study vaccines 
[eg, polysorbate 80, ethylenediaminetetraacetic acid (EDTA) or L-histidine for 
Ad26.ZEBOV vaccine; tris (hydroxymethyl)-amino methane (THAM) for MVA-BN-Filo 
vaccine]), including known allergy to egg, egg products and aminoglycosides.
5. Subject with acute illness (this does not include minor illnesses such as diarrhea or mild 
upper respiratory tract infection) or body temperature ≥38.0ºC on Day 1 will be excluded 
from enrollment at that time, but may be rescheduled for enrollment at a later date.
6. HIV type 1 or type 2 infection.
Note: If the HIV test result is positive, in order to maintain subject confidentiality, the 
investigator will ensure adequate counseling and follow-up will be made available
especially in adolescent subjects.

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7. Criterion modified per Amendment 3
7.1.
A woman who is pregnant, breast-feeding or planning to become pregnant while 
enrolled in the study or within at least 3 months after the prime vaccination, up to 
1 month after the boost vaccination (whichever takes longer), or within at least 3 months 
after the third vaccination.
8. Presence of significant conditions (eg, history of seizure disorders, (auto)immune disease 
or deficiency, any spleen disease, active malignancy, ongoing tuberculosis treatment, 
other systemic infections) or clinically significant findings during screening of medical 
history, ECG (for subjects ≥18 years of age), physical examination, vital signs or 
laboratory testing for which, in the opinion of the investigator, participation would not be 
in the best interest of the subject (eg, compromise the safety or well-being) or that could 
prevent, limit, or confound the protocol-specified assessments.
Note: Subjects who have recently received treatment for acute, uncomplicated malaria 
are eligible for participation if at least 3 days have elapsed from the conclusion of a 
standard, recommended course of therapy for malaria; subjects who are acutely ill with 
malaria at the time of screening should complete therapy and wait an additional 3 days 
after completion before screening for the study.
Note: Subjects with sickle cell trait can be included.
9. Criterion modified per Amendment 3
9.1.
History of or underlying liver or renal insufficiency, or significant cardiac, vascular, 
pulmonary (eg, persistent asthma), gastrointestinal, endocrine, neurologic, hematologic, 
rheumatologic, psychiatric or metabolic disturbances.
10. History of malignancy other than squamous cell or basal cell skin cancer, unless there has 
been surgical excision that is considered cured. Subjects with malignancies who are 
currently being treated or are not surgical cures are excluded.
11. Major surgery (per the investigator’s judgment) within the 4 weeks prior to screening or 
planned major surgery through the course of the study (from screening until completion 
of the study, see Section 10.1).
12. Post-organ and/or stem cell transplant whether or not with chronic immunosuppressive 
therapy.
13. Receipt of any disallowed therapies as noted in Section 8 before the planned 
administration of the prime vaccine on Day 1.
14. Received an investigational drug or investigational vaccine or used an invasive 
investigational medical device within 3 months prior to screening, or current or planned 
participation in another clinical study during the study. 
Note: Participation in an observational clinical study is allowed.
15. Criterion modified per Amendment 2
15.1. Donation of a unit of blood within 8 weeks before Day 1 or plans to donate blood until 
42 days post-last vaccination.

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16. Receipt of blood products or immunoglobulin within 3 months prior to screening and 
during participation in the study.
17. Current or past abuse of alcohol, recreational or narcotic drugs,
which in the 
investigator’s opinion would compromise the subject’s safety and/or compliance with the 
study procedures.
18. History of chronic urticaria (recurrent hives).
19. Subject cannot communicate reliably with the investigator.
20. Subject who, in the opinion of the investigator, is unlikely to adhere to the requirements 
of the study.
21. Employee of the investigator or study site, with direct involvement in the proposed study 
or other studies under the direction of that investigator or study site, as well as family
members of the employees or the investigator. 
Additional Exclusion Criteria for HIV-infected Subjects
4.2.2.
HIV-infected subjects must not meet any of the exclusion criteria for healthy adult and elderly 
subjects (see Section 4.2.1) with the exception of #6 which is not applicable to this population.
Exclusion Criteria for Pediatric Subjects 
4.2.3.
Any potential subject who meets any of the following criteria will be excluded from participating 
in the study:
22. Has received any candidate Ebola vaccine.
23. Diagnosed with Ebola virus disease, or prior exposure to Ebola virus, including travel to 
epidemic Ebola areas less than 1 month prior to screening. 
24. Has received any experimental candidate Ad26- or MVA-based vaccine in the past.
Note: Receipt of any approved vaccinia/smallpox vaccine or Ad-based candidate vaccine 
other than Ad26 at any time prior to study entry is allowed.
25. 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, EDTA or L-histidine for Ad26.ZEBOV vaccine; THAM for 
MVA-BN-Filo vaccine]), including known allergy to egg, egg products and 
aminoglycosides, or to neomycin or streptomycin.
26. Subject with acute illness (this does not include minor illnesses such as diarrhea or mild 
upper respiratory tract infection) or body temperature ≥38.0ºC on Day 1 will be excluded 
from enrollment at that time, but may be rescheduled for enrollment at a later date.
27. Criterion modified per Amendment 3
27.1. HIV type 1 or type 2 infection.
Note: If the HIV test result is positive, in order to maintain subject confidentiality, the 
investigator will ensure adequate counseling and follow-up will be made available.

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28. A female subject who is pregnant, breast-feeding or planning to become pregnant while 
enrolled in the study or within 3 months after the prime vaccination or up to 1 month 
after the boost vaccination (whichever takes longer). 
29. Criterion modified per Amendment 3
29.1. Weight-per-height below 10th percentile according to the Centers for Disease Control 
and Prevention (CDC) growth charts (4- to 11-year-olds).5
30. Presence of significant conditions (eg, history of seizure disorders, (auto)immune disease 
or deficiency, any spleen disease, active malignancy, ongoing tuberculosis treatment, 
other systemic infections) or clinically significant findings during screening of medical 
history, physical examination, laboratory testing or vital signs for which, in the opinion of 
the investigator, participation would not be in the best interest of the subject 
(eg, compromise the safety or well-being) or that could prevent, limit, or confound the 
protocol-specified assessments.
Note: Subjects who have recently received treatment for acute, uncomplicated malaria 
are eligible for participation if at least 3 days have elapsed from the conclusion of a 
standard, recommended course of therapy for malaria; subjects who are acutely ill with 
malaria at the time of screening should complete therapy and wait an additional 3 days 
after completion before screening for the study.
31. Criterion modified per Amendment 3
31.1 History of or underlying liver or renal insufficiency, or significant cardiac, vascular, 
pulmonary (eg, persistent asthma), gastrointestinal, endocrine, neurologic, hematologic, 
rheumatologic, psychiatric or metabolic disturbances.
32. Major congenital anomalies or known cytogenetic disorders (eg, Down’s syndrome). 
Subjects with sickle cell trait can be included.
33. Major surgery (per the investigator’s judgment) within the 4 weeks prior to screening or 
planned major surgery through the course of the study (from screening until completion 
of the study, see Section 10.1).
34. Receipt of any disallowed therapies as noted in Section 8 before the planned 
administration of the prime vaccine on Day 1.
35. Received an investigational drug or investigational vaccine or used an invasive 
investigational medical device within 3 months prior to screening, or current or planned 
participation in another clinical study during the study.
Note: Participation in an observational clinical study is allowed.
36. Receipt of blood products or immunoglobulin within 3 months prior to screening and 
during participation in the study.
37. History of chronic urticaria (recurrent hives), eczema and/or atopic dermatitis.
38. Criterion modified per Amendment 2
38.1. Subject lives in an orphanage.

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39. Subject’s parent(s)/legal guardian cannot communicate reliably with the investigator.
40. Subject or parent(s)/legal guardian who, in the opinion of the investigator, is unlikely to 
adhere to the requirements of the study.
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 3
1.1.
Criterion modified per Amendment 2
1.2.
Female subjects of childbearing potential must remain on a highly effective method of 
birth control consistent with local regulations regarding the use of birth control methods 
for subjects participating in clinical studies (see inclusion criteria) until at least 3 months 
after the prime vaccination or up to 1 month after the boost vaccination (whichever takes
longer). If the social situation of a female subject changes after start of the study 
(eg, female subject who is not heterosexually active becomes active), she must begin a 
highly effective method of birth control, as described above in Sections 4.1 and 4.2, until 
at least 3 months after the prime vaccination or up to 1 month after the boost vaccination 
(whichever takes longer).* Female subjects of childbearing potential participating in the 
Cohort 1 substudy will be asked to use adequate birth control measures for sexual 
intercourse from at least 14 days before to at least 3 months after the third vaccination.
Note: A period of 3 months after vaccination with Ad26.ZEBOV and 1 month after 
vaccination with MVA-BN-Filo should be respected, whichever takes longer. 
Note: Prior to each study vaccine administration, a urine pregnancy test should be 
performed for female subjects of childbearing potential.
2. Criterion modified per Amendment 3
2.1.
Criterion modified per Amendment 2
2.2.
Male subjects who did not have a vasectomy performed more than 1 year prior to 
screening and who are sexually active with a female subject of childbearing potential 
must use condoms for sexual intercourse until at least 3 months after the prime 
vaccination or up to 1 month after the boost vaccination (whichever takes longer).* Male 
subjects participating in the Cohort 1 substudy who did not have a vasectomy performed 
more than 1 year prior to the third vaccination and who are sexually active with a female 
subject of childbearing potential must use condoms for sexual intercourse until at least 
3 months after the third vaccination.
*After unblinding (see Sections 3.1 and 11 for details), subjects who received 
placebo may stop birth control measures or resume their pre-study birth control 
measures.

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3. Criterion modified per Amendment 3
3.1.
Women should not breast-feed while enrolled in the study until at least 3 months after 
the prime vaccination or up to 1 month after the boost vaccination (whichever takes
longer). Women participating in the Cohort 1 substudy should not breast-feed while 
enrolled in the study until at least 3 months after the third vaccination.
4. Criterion modified per Amendment 3
4.1.
Criterion modified per Amendment 2
4.2.
Traveling to epidemic Ebola areas is prohibited while enrolled in the study from the 
start of screening onwards until the 42-day post-last vaccination (excluding third 
vaccination) or 21-day post third vaccination visit. Subjects who subsequently travel to
these areas should have returned at least 1 month before the long-term follow-up visits 
(6 months post-last vaccination and Day 365 [1 year post third vaccination for Cohort 1 
substudy]). Any traveling to epidemic Ebola areas should be documented in the case 
report form (CRF). 
Note: Subjects travelling to epidemic Ebola areas will be excluded from follow-up 
collection of blood for immunogenicity assessments if they contract Ebola virus disease
(see also exclusion criterion #2 and #23 in Sections 4.2.1 and 4.2.3, respectively).
5. Subjects should not use any disallowed therapies as described in Section 8.
5.
TREATMENT ALLOCATION AND BLINDING
Vaccination Schedule Allocation
Based on the subject’s demographics, a subject will be enrolled in one of the cohorts at study 
entry. Central randomization will be implemented in this study. In Cohort 1, subjects will be 
enrolled in parallel and randomized in a 1:1:1 ratio to Groups 1, 2 and 3 at baseline until a target 
of 132 subjects have been included in Group 3. Afterwards, randomization in this cohort will 
proceed in a 1:1 ratio to Groups 1 and 2. In Cohorts 2a, 2b, and 3, subjects will be enrolled in 
parallel and randomized in a 1:1 ratio to Groups 1 and 2 at baseline. Subjects will be randomly 
assigned to groups within cohorts (stratified by PBMC sampling capability of the selected sites), 
and within groups and age strata randomly assigned to Ad26.ZEBOV and MVA-BN-Filo, or 
placebo in a 5:1 ratio, based on a computer-generated randomization schedule prepared before 
the study by or under the supervision of the sponsor. The randomization within each group will 
be balanced by using randomly permuted blocks. Within Cohort 1, there will be stratification by 
age group (adults: ≥18 to ≤50 years of age, versus elderly: >50 years of age). The interactive web 
response system (IWRS) will assign a unique code, which will dictate the assignment and 
matching vaccination schedule for the subject. The requestor must use his or her own user 
identification and personal identification number when contacting the IWRS, and will then give 
the relevant subject details to uniquely identify the subject. For participants of the substudy, 
subjects who received Ad26.ZEBOV and MVA-BN-Filo will receive Ad26.ZEBOV as third 
vaccination. Subjects who received placebo will receive placebo as third vaccination.

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Blinding
For each cohort, subjects and study-site personnel will be blinded to the study vaccine allocation 
within groups until the last subject in that cohort has completed the study. A subject will be 
considered to have completed the study if he or she has completed all assessments at the 6-month
post-boost vaccination visit or at the Day 365 (1-year post third vaccination for Cohort 1 
substudy)
visit, whichever occurs later. Qualified study-site personnel with primary 
responsibility for study vaccine preparation and dispensing, and not involved in any other
study-related procedure will be unblinded to the study vaccine allocation. The study vaccines 
will be administered by a blinded study vaccine administrator (see Definitions of Terms).
For each cohort, sponsor personnel will be blinded to study vaccine allocation within groups 
until the last subject in that cohort has completed the 6-month post-boost visit or discontinued 
earlier. All subjects within a cohort will be followed in a blinded manner by the site until the last 
subject in that cohort has completed the study. Any subject who completed either the 6-month 
post-prime and/or the Day 365 visit prior to approval of Amendment 2 was required to attend the 
6-month post-boost and the Day 365 visit after approval of Amendment 2. Refer to Sections 3.1
and 11 for further details on unblinding and primary and interim analyses.
The investigator will not be provided with randomization codes. The codes will be maintained 
within the IWRS, which has the functionality to allow the investigator to break the blind for an 
individual subject.
Data that may potentially unblind the study vaccine assignment (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 can include making special provisions, such as segregating the data in question from view 
by the investigators, clinical team, or others as appropriate until the time of database lock and 
unblinding. The pharmacy and preparation of study vaccines will be monitored by an 
independent study vaccine monitor (see Section 17.8).
Under normal circumstances, the blind for the sponsor should not be broken within a cohort until 
the last subject in that cohort has completed the 6-month post-boost visit or discontinued earlier. 
Otherwise, the blind should be broken only if 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 study vaccine by contacting the IWRS. It is 
recommended that the investigator contacts the sponsor or its designee if possible to discuss the 
particular situation, before breaking the blind. Telephone contact with the sponsor or its designee 
will be available 24 hours per day, 7 days per week. In the event the blind is broken, the sponsor 
must be informed as soon as possible. The date and reason for the unblinding must be 
documented by the IWRS, in the appropriate section of the CRF, and in the source document. 
The documentation received from the IWRS indicating the code break must be retained with the 
subject's source documents in a secure manner. 
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 

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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
An overview of the study vaccination schedules is provided in Table 1.
Table 1:
Study Vaccination Schedules Groups 1-3
Cohort
N (per group)
Prime 
(D1)
Boost
(D29, D57 or D85)
1
Healthy adult and elderly subjects (18-70 years inclusive)
264 
(Groups 1 & 2)
220
Ad26.ZEBOV 5x1010 vp
MVA-BN-Filo 1x108 Inf U
44
placebo 
placebo
132
(Group 3)
110
Ad26.ZEBOV 5x1010 vp
MVA-BN-Filo 1x108 Inf U
22
placebo 
placebo
2a
HIV-infected subjects (18-50 years inclusive)
66
55
Ad26.ZEBOV 5x1010 vp
MVA-BN-Filo 1x108 Inf U
11
placebo
placebo
2b
Adolescents (12-17 years inclusive)
66
55
Ad26.ZEBOV 5x1010 vp
MVA-BN-Filo 1x108 Inf U
11
placebo
placebo
3
Children (4-11 years inclusive)
66
55
Ad26.ZEBOV 5x1010 vp
MVA-BN-Filo 1x108 Inf U
11
placebo
placebo
Inf U: infectious units; N: number of subjects per group to receive study vaccine; vp: viral particles
Table 2: 
Cohort 1 Substudy Vaccination Schedule (Groups 1-2, Selected Sites)
Cohort
N (total Groups 1-2)
Third Vaccination
(at least 1 year post prime)
1
Healthy adult and elderly subjects (18-70 years inclusive)
90*
Ad26.ZEBOV 5x1010 vp
placebo 
N: total number of subjects in Groups 1 and 2 to receive study vaccine; vp: viral particles
* Subjects who received Ad26.ZEBOV and MVA-BN-Filo will receive Ad26.ZEBOV as third vaccination. Subjects who 
received placebo will receive placebo as third vaccination.
6.1.
General Instructions and Procedures
All subjects will receive a vaccination, according to randomization, on Day 1 (Groups 1 to 3) and 
on Day 29 (Group 1), Day 57 (Group 2) or Day 85 (Group 3) at the following dose levels:

Ad26.ZEBOV: 5x1010 vp, supplied in a single use vial (0.5 mL extractable).

MVA-BN-Filo: 1x108 Inf U (nominal titer; target fill is 1.9x108 Inf U per dose, range: 
1.27-2.67x108 Inf U), supplied in a single use vial (0.5 mL extractable).

Placebo: 0.9% saline (0.5 mL extractable).

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At selected sites, approximately 90 healthy adult subjects in Cohort 1 (Groups 1 and 2) will 
receive a third vaccination with Ad26.ZEBOV at 5x1010 vp or placebo at least 1 year post prime 
vaccination (substudy).
Study vaccines (Ad26.ZEBOV, MVA-BN-Filo or placebo) will be administered as 0.5-mL IM 
injections into the deltoid muscle by a blinded study vaccine administrator (see Definitions of 
Terms). In each subject, the boost vaccination should preferably be administered in the opposite 
deltoid from the prime vaccination (unless local site reaction cannot be assessed reliably in the 
opposite arm) and it should be recorded in the CRF in which arm the vaccination has been 
administered. The injection site should be free from any injury, local skin problem, significant 
tattoo or other issue that might interfere with evaluating the arm after injection (eg, subjects with 
a history of skin cancer must not be vaccinated at the previous tumor site). No local or topical 
anesthetic will be used prior to the injection. The third vaccination can be administered in either 
deltoid.
Discontinuation of study vaccine administration should occur in any subject meeting the criteria 
outlined in Section 10.2. Criteria for postponement of vaccination and contraindications to boost
and third vaccinations have been defined in Sections 6.2 and 6.3, respectively. Refer to 
Section 9.3.2 for details on the pre-specified pausing rules to halt vaccination of further subjects. 
Subjects will remain at the site for a total of 60 (±15) minutes (after prime and boost 
vaccinations) or 30 (±15) minutes (after the third vaccination) post-vaccination to monitor for the 
development of any acute reactions, or longer if deemed necessary by the investigator (eg, in 
case of grade 3 adverse events). As with any vaccine, allergic reactions following vaccination 
with the study vaccine are possible. Therefore, appropriate drugs and medical equipment to treat 
acute anaphylactic reactions must be immediately available and a medically qualified member of 
study-site personnel trained to recognize and treat anaphylaxis must be present in the clinic 
during the entire vaccination procedure and post-vaccination monitoring period.
The investigator must provide emergency care as needed for any subject who experiences a life-
threatening event. All sites will have facilities, equipment and the ability to manage an 
anaphylactic reaction. If additional therapy is required, the investigator will arrange for transport 
to the closest appropriate facility for continuing care.  
The Site Investigational Product Procedures Manual specifies the maximum time that will be 
allowed between preparation and administration of the study vaccine.

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6.2.
Criteria for Postponement of Vaccination
A subject will not be given the prime, boost, or third (Cohort 1 substudy only) vaccination if 
he/she experiences any of the following events at the scheduled time for vaccination:

Acute illness at the time of vaccination (this does not include minor illnesses such as 
diarrhea or mild upper respiratory tract infection);
Note: If a subject is acutely ill with malaria at the time of either prime, boost, or third
vaccination, at least 3 days must elapse from the conclusion of a standard, recommended 
course of therapy for malaria before vaccination.

Fever (body temperature ≥38.0°C) at the time of vaccination.
Subjects experiencing any of the events described above may be vaccinated up to 10 days 
beyond the window allowed for the scheduled vaccination, or be withdrawn from that 
vaccination at the discretion of the investigator and after consultation with the sponsor (see 
Section 10.2).
Note: In case the boost or third vaccination is postponed, the timing of the post-boost or post 
third vaccination visits will be planned relative to the actual vaccination day (see Sections 9.1.1
and 9.1.7).
6.3.
Contraindications to Boost and Third Vaccinations
A subject will not be given the boost or third vaccination if he or she experiences any of the 
following events at any time after the prime or boost vaccination, respectively: 
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 prime vaccination.
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 as 
described in Section 10.2.
An ad hoc IDMC meeting may be requested via the sponsor for any single event or combination 
of multiple events which are considered to jeopardize the safety of the subjects.

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7.
TREATMENT COMPLIANCE
All study vaccines will be administered on site by a blinded study vaccine administrator (see 
Definitions of Terms). The date and time of each study vaccine administration will be recorded 
in the CRF.
8.
PRESTUDY AND CONCOMITANT THERAPY
Prestudy therapies administered up to 30 days prior to the start of screening and previous 
vaccinia/smallpox vaccination at any time prior to study entry must be recorded in the CRF. 
Concomitant therapies must be recorded from screening onwards until 42 days after the last 
vaccination (excluding third vaccination). For subjects in the Cohort 1 substudy, concomitant 
therapies should be recorded again from the day of the third vaccination until 28 days post third 
vaccination. Thereafter, concomitant therapies are only to be recorded if given in conjunction 
with serious adverse events and IREs that meet the criteria outlined in Sections 12.3.2
and 12.3.3, respectively. Any vaccines received during the study should be recorded. 
All therapies (prescription or over-the-counter medications, including vaccines, vitamins, herbal 
supplements; non-pharmacologic therapies such as electrical stimulation, acupuncture, special 
diets, exercise regimens) must be recorded in the CRF. Recorded information will include a 
description of the type of the drug, treatment period, dosing regimen, route of administration, and 
its indication.
Subjects must use adequate birth control measures prior to randomization as described in 
Section 4.
Subjects are allowed to receive all routine immunizations (including rotavirus for pediatric 
subjects) according to local vaccination schedules, taking into account the following restrictions:

Routine immunizations with inactivated vaccines (including rotavirus for pediatric subjects) 
should be administered at least 15 days before or after administration of any study vaccine 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. 

Routine immunizations with live attenuated vaccines are prohibited in the period from 
30 days before baseline (Day 1) to 30 days after the last vaccination.
However, if a vaccine is indicated in a post-exposure setting (eg, rabies or tetanus), it must take 
priority over the study vaccine.
Analgesic/antipyretic medications and nonsteroidal anti-inflammatory drugs may be used 
post-vaccination only in case of medical need (eg, body temperature ≥38.0°C or pain) and their 
use must be documented. Use of these medications as routine prophylaxis prior to study vaccine 
administration is prohibited.
Chronic or recurrent use of medications that modify the host immune response (eg, cancer 
chemotherapeutic agents, systemic corticosteroids, immunomodulators) are prohibited. 

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HIV-infected subjects must be on a stable HAART regimen for at least 4 weeks prior to 
screening. These medications must be documented in the concomitant medication form as a prior 
medication and any changes to their regimen must also be recorded.
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in 
which prohibited therapies are administered. Prohibited therapies will be captured as protocol 
deviations.
9.
STUDY EVALUATIONS
9.1.
Study Procedures
Refer to Section 9.1.6 for the procedures to be followed in case of a study pause and to 
Section 9.1.7 for procedures to be followed for subjects participating in the Cohort 1 substudy.
Overview
9.1.1.
The Time and Events Schedule summarizes the frequency and timing of safety, tolerability and 
immunogenicity measurements and evaluations applicable to this study. Details for all study 
procedures are provided in the following sections. Additional unscheduled study visits may be 
required if in the investigator’s opinion, further clinical or laboratory evaluation is needed.
Visit Windows
The screening visit has to be performed within 8 weeks prior to the baseline visit (ie, the day of 
the subject’s prime vaccination, Day 1). If a subject did not receive study vaccine on the planned 
day of vaccination, the timings of the next visits post-vaccination (see Time and Events 
Schedule) will be determined relative to the actual day of vaccination. Visit windows that will be 
allowed are summarized in Table 3. The subject should be encouraged to come within these time 
windows.

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Table 3:
Visit Windows
Visit Description
Day
Window 
Seven Days Post-prime Vaccination 
Day 8 for all groups
±2 days
Fourteen Days Post-prime Vaccination 
(only in Groups 2 and 3 from Cohort 1) 
Day 15 for Group 2 
and Group 3
±2 days
Boost Vaccination
Day 29 for Group 1
Day 57 for Group 2
Day 85 for Group 3
±3 days
Seven Days Post-boost Vaccination 
Day 36 for Group 1
Day 64 for Group 2
Day 92 for Group 3
±2 days
Twenty-one Days Post-boost Vaccination 
Day 50 for Group 1
Day 78 for Group 2
Day 106 for Group 3
±3 days
Forty-two Days Post-boost Vaccination 
Day 71 for Group 1
Day 99 for Group 2
Day 127 for Group 3
±3 days
Follow-up 6 Months Post-boosta
Day 209 for Group 1
Day 237 for Group 2
Day 265 for Group 3
±15 days
Follow-up 1 Year Post-prime
Day 365 for all groups
±30 days
Refer to Table 6 (Section 9.1.7) for the visit windows that will be allowed for the Cohort 1 substudy.
a Subjects who completed the 6-month post-prime visit (which has been replaced with the 6-month post-boost visit 
per protocol Amendment 2) prior to approval of Amendment 2 were required to also attend the 6-month post-boost 
visit after approval of Amendment 2.
Blood Sampling Volumes
Approximately 200 to 400 mL of blood (including PBMC samples) will be drawn from adults
and adolescents (12-17 years of age inclusive) over a period of 1 year, and remains well below
the limits of standard blood donation.
For children (<12 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. In order 
to meet the planned safety, serologic and cellular endpoints, it might be necessary to slightly 
exceed the guideline of 1% of the total blood volume at any single time. The sites will be 
instructed that the procedures should preferably be performed in the following order, according 
to their importance: safety, serology and cellular. The total volume of blood is estimated at 80 to 
90 mL/kg body weight; 3% is 2.4 mL blood per kg body weight.9 The allowable blood volume 
calculations are based on the 10th percentile for growth charts for 4- to 11-year-old children.5
For details on the approximate blood sampling volumes collected by visit and the cumulative 
blood volumes in Cohorts 1 and 2, refer to the Time and Events Schedule. For Cohort 3, the 
approximate blood sampling volumes collected by visit and the cumulative blood volumes for 
the immunogenicity assessments are provided in the Time and Events Schedule, while the site’s 
Standard Operating Procedure will be followed with regard to the blood volumes for the clinical 
laboratory assessments.

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Additional serum or urine pregnancy tests may be performed, as determined necessary by the 
investigator or required by local regulation, to establish the absence of pregnancy at any time 
during the subject's participation in the study.
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples.
Screening Phase
9.1.2.
Up to 8 weeks before baseline (the day of the subject’s prime vaccination, Day 1) and after 
signing and dating the ICF and/or assent (see Section 16.2.3), screening assessments will be 
performed as indicated in the Time and Events Schedule. Screening may be split into multiple 
days or visits. In exceptional cases, the screening phase can be extended if discussed with and 
approved (documented) by the sponsor, eg, if not all the test results become available during the 
allocated 8 weeks; this will be evaluated on a case-by-case basis.
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 were used from at least 28 days before the prime vaccination with a negative 
serum -hCG pregnancy test at screening and a negative urine test immediately prior to each 
study vaccination (see Section 4). 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 1 month after the boost vaccination 
(whichever takes longer) (see Section 4.3). 
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 
written informed consent/assent prior to each subject’s study participation. The procedures 
indicated in the Time and Events Schedule will only be performed after the subject’s written 
informed consent/assent has been obtained. 
After reading but before signing the ICF/assent, the TOU will be administered. Subjects who fail 
may repeat the test twice (and have to pass the third time to be eligible). Subjects must pass the 
TOU before starting the screening procedures. The TOU is a questionnaire to document the 
subject’s understanding of the study (for details, see Section 16.1).
The following is performed to determine eligibility requirements as specified in the inclusion and 
exclusion criteria:

Review of all inclusion and exclusion criteria;

Review of medical history (including concomitant diseases) and demographics;

Review of prestudy therapies (up to 30 days prior to the start of screening), previous 
vaccinia/smallpox vaccination if known (at any time prior to study entry; not applicable for 
Cohort 3) and concomitant therapies;

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
Serum pregnancy test (for female subjects of childbearing potential);

Blood sampling for hematology and chemistry (fasting or non-fasting);

Urine sampling for urinalysis;

Serology testing: HIV type 1 or type 2 (for Cohorts 1, 2b, and 3 only); 

CD4+ cell count for HIV-infected subjects;

FSH assessment (for women >45 years of age with amenorrhea for less than 2 years or 
≤45 years of age with amenorrhea for more than 6 months);

ECG recording for subjects ≥18 years of age;

Full physical examination (including height and body weight; a genitourinary examination is 
not required);

Measurement of vital signs (blood pressure, pulse/heart rate, body temperature).
All adverse events and pregnancies will be collected from the time a signed and dated ICF is 
obtained. 
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 screening to 
assess eligibility. The safety laboratory assessments are to be performed within 28 days prior to 
the prime vaccination (including Day 1 before vaccination) and may be repeated once if they fall 
outside this time window. If rescreening is required, all screening procedures (except TOU) 
should be repeated. Study subjects who qualify for inclusion will be contacted and scheduled for 
enrollment and prime vaccination within 8 weeks.
Vaccination Phase (Prime and Boost)
9.1.3.
If eligible, the subject will come for the baseline visit (Day 1). The investigator should ensure 
that all enrollment criteria have been met during screening. If a subject’s clinical status changes 
(including available laboratory results or receipt of additional medical records) after screening 
but before the prime vaccination (Day 1) such that the subject no longer meets all enrollment 
criteria, then the subject should be excluded from further participation in the study. If the initial 
laboratory sampling occurred more than 8 weeks before baseline (Day 1), sampling will need to 
be repeated.
Eligible subjects will be allocated (by central randomization) to a vaccination schedule as 
described in Section 5. 
The subjects will be vaccinated as described in Section 6, with prime vaccinations administered 
at Day 1 for all groups, and boost vaccinations at Day 29 (Group 1), Day 57 (Group 2) or Day 85 
(Group 3) unless any of the pre-specified criteria not to proceed with vaccination are met (refer 
to Sections 6.2, 6.3 and 10.2 for details) or if a pause for vaccination of further subjects has been 
installed (see Section 9.3.2).

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Before each vaccination (prime and boost), a urine pregnancy test (for female subjects of 
childbearing potential), a targeted physical examination and measurements of vital signs will be 
performed and blood will be drawn for safety and immunogenicity assessments. Refer to 
Section 9.4 for further details on the immunogenicity evaluations. 
Study vaccine will be prepared on-site by unblinded qualified study-site personnel not involved 
in any other study-related procedure who will place a blinding tape on the syringe to mask its 
content and send the vaccine to a blinded study vaccine administrator (see Definitions of Terms)
for administration to the subject (see Section 14.3 for details). Refer to Section 6 for further 
details on dosage and administration and post-vaccination monitoring.
All adverse events, serious adverse events, IREs and pregnancies will be collected and 
documented on the CRF, together with the information on any concomitant medications. For 
reporting of IREs, refer to Section 12.3.3.
Upon discharge from the site, subjects will be provided with a diary, a thermometer, and a ruler 
to measure and record local solicited adverse events and body temperature. Subjects will also 
record solicited local and systemic adverse events (reactogenicity) in the diary in the evening 
after vaccination and then daily for the next 7 days at approximately the same time each day. 
Diaries should be completed at home by the subject (or parent, legal guardian or caregiver, as 
applicable). For illiterate subjects or those having difficulty completing the diary independently, 
the sites will make arrangements to have the diary completed according to their local practice. A 
modified diary is available for pre-verbal children. Subjects will be instructed to contact the 
investigator immediately in case they experience an unsolicited adverse event (not listed on the 
diary card) or for any severe (grade 3) solicited adverse event (listed on the diary card). 
Subjects in Groups 2 and 3 from Cohort 1 will come for an additional visit on Day 15, and will 
have blood drawn for immunogenicity assessments. 
In all groups, subjects will come to the site at 7 days after each vaccination as indicated in the 
Time and Events Schedule. The subject’s diary will be reviewed by study-site personnel. The 
investigator will examine the injection site for occurrences of erythema, induration/swelling, 
pain/tenderness or itching at these visits in order to complete the relevant parts of the CRF. 
Blood samples will be taken for safety (all subjects, after each vaccination) and immunogenicity 
(Cohorts 1 and 2a only, after boost vaccination) evaluations.
Post-vaccination Phase
9.1.4.
In all groups, subjects will come to the site at 21 and 42 days after the boost vaccination as 
indicated in the Time and Events Schedule. The investigator will examine the injection site for 
occurrences of erythema, induration/swelling, pain/tenderness or itching at these visits in order to 
complete the relevant parts of the CRF. 
All adverse events, serious adverse events, IREs and pregnancies will be collected and 
documented on the CRF, together with the information on any concomitant medications. For 
reporting of IREs, refer to Section 12.3.3.

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Subjects will also have blood drawn for immunogenicity assessments at the specified visits in the 
Time and Events Schedule. Refer to Section 9.4 for further details on the immunogenicity 
evaluations.
Subjects will be instructed to contact the investigator before the next visit (ie, 6 months post-
boost) if they experience any adverse event or intercurrent illness that they perceive as relevant 
and/or can be possibly related to study vaccine in their opinion. 
Long-term Follow-up
9.1.5.
When all subjects in a cohort have completed their 6-month post-boost visit or discontinued 
earlier, that cohort will be unblinded to the sponsor. All subjects within a cohort will be followed 
in a blinded manner by the site until the last subject in that cohort has completed the study. Any 
subject who completed either the 6-month post-prime and/or the Day 365 visit prior to approval 
of Amendment 2 was required to attend the 6-month post-boost and the Day 365 visit after 
approval of Amendment 2.
Serious adverse event information and IREs will be collected until the end of the study, and 
concomitant therapies should only be recorded if given in conjunction with serious adverse 
events and IREs. Pregnancies will be reported until the end of the study. Subjects will have blood 
drawn for immunogenicity assessments at the 6-month post-boost and Day 365 visits. Refer to 
Section 9.4 for further details on the immunogenicity evaluations. Physical examinations will be 
performed as indicated in the Time and Events Schedule.
Approximately 90 healthy adult subjects in Cohort 1 (Groups 1 and 2, at selected sites) will 
participate in a substudy. Refer to Section 9.1.7 for procedures to be followed for subjects 
participating in the Cohort 1 substudy.
Procedures in Case of a Study Pause
9.1.6.
A study pause can affect subjects that are either awaiting prime vaccination or boost vaccination. 
After approval is granted to restart the study, subjects who are awaiting prime vaccination and 
whose screening period is longer than the protocol-defined 8 weeks as a result of the study 
pause, will be allowed to rescreen once (following the screening procedures described in 
Section 9.1.2, excluding TOU). These subjects need to sign a new ICF/assent. Subjects that are 
rescreened due to the pause must have new safety laboratory assessments (including HIV, FSH 
[if applicable], ECG, hematology, biochemistry, urinalysis, vital signs and physical examination)
within 28 days of the prime vaccination. The TOU does not need to be repeated. After screening, 
these subjects will follow the same study procedures as those subjects who were unaffected by 
the study pause (described in Sections 9.1.3 to 9.1.5).
Subjects who are outside the protocol-defined boost vaccination window due to the study pause 
may choose to receive a late boost vaccination, if allowed by the sponsor and/or the relevant 
oversight authorities. Visit windows for the subjects who elect to receive a late boost vaccination 
are summarized in Table 4. These subjects need to sign a specific ICF/assent. Subjects who agree 

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to the late boost vaccination will follow the same post-boost vaccination schedule as those 
subjects whose boost vaccination was unaffected by the study pause (see Section 9.1.4). 
Note: For female subjects of childbearing potential, it should be confirmed that adequate birth 
control measures were used from at least 28 days before the prime vaccination and boost 
vaccination, with a negative serum -hCG pregnancy test at screening and a negative urine test 
immediately prior to each study vaccination (see Section 4). 
Table 4: 
Visit Windows for Subjects Who Elect to Receive a Late Boost Vaccination
Visit Description
Day
Window 
Seven Days Post-prime Vaccination 
Day 8 for all groups
±2 days
Fourteen Days Post-prime Vaccination 
(only in Groups 2 and 3 from Cohort 1) 
Day 15 for Group 2 
and Group 3
±2 days
Boost Vaccination
Seven Days Post-boost Vaccination
±2 days
Twenty-one Days Post-boost Vaccination 
±3 days
Forty-two Days Post-boost Vaccination 
±3 days
Follow-up 6 Months Post-boost
±15 days
Follow-up 1 Year Post-prime
Day 365 for all groups
±30 days
Visit windows for the subjects who are not willing or not allowed to receive a late boost 
vaccination are summarized in Table 5. These subjects need to sign a specific ICF/assent. All 
post-prime vaccination visits need to be performed despite the interruption in dosing. After the 
7-day post-prime and 14-day post-prime (only in Groups 2 and 3 from Cohort 1) visits, these 
subjects will be followed every 3 months after the prime vaccination for safety only (and 
immunogenicity on the 6-month and 1-year post-prime visits), until Day 365 (see Additional 
Time and Events Schedule for subjects who do not receive a boost vaccination because of a 
study pause). Information for these time points (except for the 6-month and 1-year post-prime 
visits) may be collected either by telephone contact, visit to the site or by a home visit, according 
to local practice. For subjects in Groups 2 and 3 from Cohort 1, failure to obtain the blood 
samples for immunogenicity assessments on the additional visit on Day 15 will be considered as 
a minor protocol deviation.

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Table 5: 
Visit Windows for Subjects Who are Not Willing or Not Allowed to Receive the Late Boost 
Vaccination
Visit Descriptiona
Day
Window 
Seven Days Post-prime Vaccination 
Day 8 for all groups
±2 days
Fourteen Days Post-prime Vaccination 
(only in Groups 2 and 3 from Cohort 1) 
Day 15 for Group 2 
and Group 3
±2 days
Three Months Post-prime Vaccinationb
Day 90 for all groups
±30 days
Six Months Post-prime Vaccination
Day 180 for all groups
±30 days
Nine Months Post-prime Vaccinationb
Day 270 for all groups
±30 days
One Year Post-prime vaccination
Day 365 for all groups
±30 days
a Subjects will be asked to return to the site approximately every 3 months after the prime vaccination for safety 
assessments, until the 1-year post-prime follow-up visit (note: the 3-month and 9-month post-prime visits may be 
conducted by best local practice, see footnote b). In case the subject is unable to return for these visits, this will not 
constitute a major protocol deviation and subjects will be considered lost to follow-up.
b The 3-month and 9-month post-prime visits may be conducted by best local practice: either by telephone contact, 
site visit or home visit.
Adverse events, whether serious or non-serious, will be collected at all visits from signing of the 
ICF onwards until 42 days after the last vaccination (ie, Day 42 post-prime vaccination for 
subjects who did not receive a boost vaccination). Thereafter, reporting will be limited to all 
serious adverse events and IREs up to the subject’s last study-related procedure. Solicited local 
and systemic adverse events (reactogenicity, see below) will be reported by the subject until 
7 days after each administration of study vaccine. Adverse events will be followed by the 
investigator as specified in Section 12. Subjects will be instructed to contact the investigator 
before the next visit (ie, 6 months post-boost visit, or 3 months post-prime visit for subjects who 
are not willing or not allowed to receive a late boost vaccination) if they experience any adverse 
event or intercurrent illness that they perceive as relevant and/or can be possibly related to study 
vaccine in their opinion. 
Subjects will have blood drawn for immunogenicity assessments as indicated in the Time and 
Events Schedule and Additional Time and Events Schedule (for subjects who do not receive a 
boost vaccination because of a study pause). Refer to Section 9.4 for further details on the 
immunogenicity evaluations. Physical examinations and vital signs will be performed as 
indicated in the Time and Events Schedule and Additional Time and Events Schedule (for 
subjects who do not receive a boost vaccination because of a study pause).

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Cohort 1 Substudy (Third Vaccination)
9.1.7.
The Cohort 1 Substudy Time and Events Schedule summarizes the frequency and timing of 
safety, tolerability and immunogenicity measurements and evaluations applicable to this 
substudy. Details for all study procedures are provided in the following paragraphs. Additional 
unscheduled study visits may be required if in the investigator’s opinion, further clinical or 
laboratory evaluation is needed.
Subjects who received a late boost vaccination or did not receive the boost vaccination at all due 
to a study pause will not be included in the Cohort 1 substudy. 
Visit Windows
If a subject did not receive study vaccine on the planned day of vaccination, the timings of the 
next visits post-vaccination (see Cohort 1 Substudy Time and Events Schedule) will be 
determined relative to the actual day of vaccination. Visit windows that will be allowed are 
summarized in Table 6. The subject should be encouraged to come within these time windows.
Table 6: 
Visit Windows
Visit Description
Daya
Window 
Third Vaccination (12-15m pp)
3rd Vaccination
Four Days Post Third Vaccination
Day 5 Post 3rd Vaccination
±1 days
Seven Days Post Third Vaccination
Day 8 Post 3rd Vaccination
±2 days
Twenty-one Days Post Third Vaccination
Day 22 Post 3rd Vaccination
±3 days
Follow-up 6 Months Post Third Vaccination 
Day 180 Post 3rd Vaccination
±15 days
Follow-up 1 Year Post Third Vaccination 
Day 365 Post 3rd Vaccination
±30 days
a The day of administration of the third vaccination is Day 1 of the substudy. Similarly, D2 Post 3rd vaccination is the 
second day of the substudy, ie, 1 day after the third vaccination.
Blood Sampling Volumes
During the Cohort 1 substudy, approximately 80 mL (or 200 mL, in case optional PBMC 
samples are taken) of blood will be drawn over a period of 1 year, which remains well below the 
limits of standard blood donation.
For details on the approximate blood sampling volumes collected by visit and the cumulative 
blood volumes in the Cohort 1 substudy, refer to the Cohort 1 Substudy Time and Events 
Schedule.
Additional serum or urine pregnancy tests may be performed, as determined necessary by the 
investigator or required by local regulation, to establish the absence of pregnancy at any time 
during the subject's participation in the Cohort 1 substudy.
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples.
Subjects participating in the Cohort 1 substudy need to sign an additional ICF before the first 
substudy-related activity. 

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All male and female subjects participating in the Cohort 1 substudy, except for female subjects 
of non-childbearing potential, will be asked to use adequate birth control measures for sexual 
intercourse from at least 14 days before to at least 3 months after the third vaccination.
Before the third vaccination, a urine pregnancy test (for female subjects of childbearing 
potential), a targeted physical examination and measurements of vital signs will be performed.
Subjects will have blood drawn for immunogenicity assessments as indicated in the Cohort 1 
Substudy Time and Events Schedule. Refer to Section 9.4 for further details on the 
immunogenicity evaluations. Physical examinations will be performed as indicated in the
Cohort 1 Substudy Time and Events Schedule.
Study vaccine will be prepared on-site by unblinded qualified study-site personnel not involved 
in any other study-related procedure who will place a blinding tape on the syringe to mask its 
content and send the vaccine to a blinded study vaccine administrator (see Definitions of Terms)
for administration to the subject (see Section 14.3 for details). Refer to Section 6 for further 
details on dosage and administration and post-vaccination monitoring.
Adverse events, whether serious or non-serious, will be collected at all visits from the day of the 
third vaccination onwards until 28 days thereafter. Thereafter, reporting will be limited to all 
serious adverse events and IREs up to the subject’s last study-related procedure. Solicited local 
and systemic adverse events (reactogenicity, see below) will be reported by the subject until 
7 days after each administration of study vaccine. Adverse events will be followed by the 
investigator as specified in Section 12. Subjects will be instructed to contact the investigator 
before the next visit if they experience any adverse event or intercurrent illness that they perceive 
as relevant and/or can be possibly related to study vaccine in their opinion. 
VAC52150 Vaccine Development Roll-over Study
9.1.8.
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 placebo) and children born to vaccinated female subjects who becam e 
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 placebo) (unless local 
regulations have additional requirements for follow-up) will be eligible for enrollment into the 
VAC52150 Vaccine Development Roll-over study for long-term surveillance (for a total of up to 
60 months after the prime vaccination). After unblinding, only female subjects and the children
of female subjects enrolled in this study who received Ad26.ZEBOV and/or MVA-BN-Filo will 
remain in the VAC52150 Vaccine Development Roll-over study for long-term safety 
surveillance. After unblinding, female subjects and the children of female subjects who received 
placebo and have already been enrolled into the VAC52150 Vaccine Development Roll-over 
study will be discontinued from further participation in the roll-over study.
9.2.
Endpoints
Refer to Section 11.1 for an overview of safety and immunogenicity endpoints.

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9.3.
Safety Evaluations
Safety Assessments
9.3.1.
The study will include the following evaluations of safety and tolerability as described below and 
according to the time points provided in the Time and Events Schedule. Any clinically 
significant abnormalities occurring from signing of the ICF onwards until 42 days after the last
vaccination (excluding third vaccination), and again from the day of the third vaccination until 
28 days thereafter for subjects in the Cohort 1 substudy, must be recorded on the Adverse Event 
section of the CRF. Thereafter, reporting will be limited to all serious adverse events and IREs. 
Any clinically significant abnormalities (including those persisting at the end of the study/early 
withdrawal) will be followed by the investigator until resolution or until a clinically stable 
endpoint is reached (see Section 12). For reporting of IREs, refer to Section 12.3.3.
The investigators, together with the sponsor’s medical monitor, will be responsible for the safety 
monitoring of the study, and will halt vaccination of further subjects in case any of the 
pre-specified pausing rules described in Section 9.3.2 have been met. Further safety measures 
with regards to vaccination are described in Sections 6.2 and 6.3.
An IDMC will be appointed by the sponsor formed with recommendations from the Clinical 
Steering Committee before the start of the study to perform regular review of the safety data 
during the study. Details regarding the IDMC are provided in Section 11.8.
Adverse Events
All adverse events, whether serious or non-serious, will be collected at all visits from signing of 
the ICF onwards until 42 days after the last vaccination (excluding third vaccination), and again 
from the day of the third vaccination until 28 days thereafter for subjects in the Cohort 1 
substudy. Thereafter, reporting will be limited to all serious adverse events and IREs up to the 
subject’s last study-related procedure. Solicited local and systemic adverse events 
(reactogenicity, see below) will be reported by the subject until 7 days after each administration 
of study vaccine. Adverse events will be followed by the investigator as specified in Section 12.
Solicited Adverse Events
Solicited adverse events (see Definitions of Terms) are precisely defined events that subjects are 
specifically asked about and which are noted by subjects in the diary. The subjects will be 
closely observed by study-site personnel for the first 30 (±10) minutes after each administration 
of study vaccine and again at 60 (±15) minutes after prime and boost vaccinations, and any 
unsolicited, solicited local or systemic adverse events will be documented during this period.
Upon discharge from the site, subjects will receive a diary, a thermometer and a ruler to measure 
body temperature and solicited local reactions. Subjects will be instructed to record solicited 
local and systemic adverse events in the diary in the evening after each administration of study 
vaccine and then daily for the next 7 days (until the 7-day post-vaccination visits) at 
approximately the same time each day to serve as a reminder to the subject for the next visit. On 
the 7-day post-vaccination visits, the diary needs to be completed on site before the subject 
leaves the site. The investigator should discuss the information from the diary with the subject, 

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document the relevant information in the clinic chart, and complete the relevant parts of the CRF 
as described in the CRF Completion Guidelines.
On-site and diary reported solicited adverse events will be captured on a separate CRF page as 
described in the CRF Completion Guidelines, in contrast to the unsolicited adverse events which 
will be reported on the Adverse Event page of the CRF. The investigator must record in the CRF 
his/her opinion concerning the relationship of the adverse event to study vaccine.
Solicited Local (Injection Site) Adverse Events
Subjects will also be instructed on how to note occurrences of erythema, induration/swelling 
(measured using the ruler supplied), pain/tenderness and itching at the injection site in the 
evening after each administration of study vaccine and then daily for the next 7 days in the diary
at approximately the same time each day. 
Solicited Systemic Adverse Events
Subjects will be instructed on how to record daily body temperature using a thermometer 
provided for home use. Subjects should record the body temperature in the evening after each 
vaccination 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. 
Subjects will also be instructed on how to note the following symptoms in the evening after each 
administration of study vaccine and then daily for the next 7 days in the diary at approximately 
the same time each day: 
Nausea/vomiting

Arthralgia

Fever
Headache

Fatigue/malaise
Myalgia

Chills
If a solicited local or systemic adverse event is not resolved the 7-day post-vaccination visit, the 
follow-up will be captured on the diary. The subject will be instructed to record the date of last 
symptoms and maximum severity in the diary after resolution.
Cardiac Events
In case any cardiac sign or symptom develops after the boost vaccination, the subject should be 
referred to a local cardiologist where the appropriate work-up which might include an ECG 
and/or troponin I assessments, if available, should be performed.  
Clinical Laboratory Tests 
Blood samples for serum chemistry and hematology, and for other tests (see below) and a urine 
sample for urinalysis will be collected at the time points indicated in the Time and Events 
Schedule. The investigator must review the laboratory results, document this review, and record 
any clinically relevant changes occurring during the study in the Adverse Event section of the 
CRF until 42 days after the last vaccination (excluding third vaccination), and again from the day 

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of the third vaccination until 28 days thereafter for subjects in the Cohort 1 substudy. Thereafter,
only serious adverse events and IREs need to be recorded. The laboratory reports must be filed
with the source documents. For reporting of IREs, refer to Section 12.3.3.
Approximate blood volume expected to be drawn per visit for clinical laboratory assessments: 

10 mL for Cohorts 1, 2a and 2b. Note: in Cohort 2a (HIV-infected subjects), an additional 2 
mL will be taken for monitoring of CD4+ cell count at screening, on Day 1, on the day of 
the boost vaccination and 42 days after the boost vaccination. 

6 mL at screening and 4 mL at other visits for Cohort 3 (4 to 11 years of age). These blood 
volumes are approximate and the site should follow their own Standard Operating 
Procedures for phlebotomy in children.
The following tests will be performed by the local laboratory, unless otherwise specified:

Hematology Panel 
-
hemoglobin
-
hematocrit
-
red blood cell count
-
white blood cell count with differential
-
platelet count

Serum Chemistry Panel 
-
sodium
-
potassium
-
blood urea nitrogen 
-
aspartate aminotransferase 
-
alanine aminotransferase 
-
total bilirubin
-
creatinine
-
FSH (in women >45 years of age with amenorrhea for less than 2 years or 
≤45 years of age with amenorrhea for more than 6 months)

Urinalysis – Dipstick
-
specific gravity
-
pH
-
glucose
-
protein
-
blood
-
ketones
In case of positive urinalysis dipstick results for >1+ protein or blood, the sediment will be 
examined microscopically (only RBC will be documented).

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Additional clinical laboratory assessments to be performed are as follows:

Serum pregnancy test for female subjects of childbearing potential at screening;

Urine pregnancy test for female subjects of childbearing potential before each study 
vaccination;

CD4+ cell count for HIV-infected subjects (Cohort 2a) at screening, on Day 1, on the day of 
the boost vaccination and at 42 days after the boost vaccination;

Serology: HIV type 1 and type 2.
Laboratory values will be determined according to the Toxicity Table for Use in Trials Enrolling 
Healthy Adults (Attachment 2) or the Toxicity Table for Use in Trials Enrolling Children Greater 
Than 3 Months of Age (Attachment 3).
Electrocardiogram
A single, 12-lead ECG will be performed for subjects ≥18 years of age at screening and 
interpreted locally. Additional ECG monitoring may be performed at other time points if 
clinically indicated. During the collection of ECGs, subjects should be in a quiet setting without 
distractions (eg, television, cell phones). Subjects should rest in a supine position for at least 
5 minutes before ECG collection and should refrain from talking or moving arms or legs. If 
blood sampling or vital sign measurement is scheduled at the same time point as ECG recording, 
the procedures should be performed in the following order: vital signs, ECG, blood draw.
Vital Signs (blood pressure, pulse/heart rate, body temperature)
Vital sign measurements will be performed at the time points indicated in the Time and Events 
Schedule. Blood pressure and pulse/heart rate measurements will be assessed (at rest) with a 
completely automated device. Manual techniques will be used only if an automated device is not 
available. Confirmatory measurements can be performed if inconsistent with a prior 
measurement.
Body temperature is preferably measured axillary. If the body temperature was measured at 
another site this needs to be captured in the CRF. 
Physical Examination 
A full physical examination including height and body weight will be performed at screening. 
Calculation of the body mass index (BMI; Cohorts 1 and 2) or growth percentiles according to 
CDC growth charts (Cohort 3; see Section 4.2.3), will be recorded in the CRF. At other visits, an 
abbreviated, symptom-directed physical examination will be performed as indicated based on 
any clinically relevant issues, clinically relevant symptoms and medical history. The symptom-
directed physical examination may be repeated if deemed necessary by the investigator. Physical 
examinations will be performed by the investigator or by a designated medically-trained 
clinician. 
A full physical examination includes the following: general appearance, eyes, ears, nose, throat, 
cardiovascular system, respiratory system, gastrointestinal system, and skin and mucous 

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membranes. A genitourinary exam is not required. A neurological and musculoskeletal 
examination as well as an examination of the lymph nodes will also be performed. An
abbreviated, symptom-directed physical examination includes examination of the injection 
site(s), heart, lungs and abdomen.
The height should be measured barefooted at the screening visit. To obtain the actual body 
weight, subjects must be weighed lightly clothed.
Pausing Rules
9.3.2.
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. These pausing rules are not applicable for the third vaccination.
Any cohort
If any of the following events occur in any subject in any cohort who received at least one dose 
of study vaccine in the study (at any site), the site investigator will halt the vaccination of further 
subjects in all cohorts and the sponsor’s medical monitor will be notified immediately. The 
sponsor’s medical monitor will inform all the other investigators to halt further vaccination as 
well.

Death in any subject, considered at least possibly related to the study vaccine; OR

An anaphylactic reaction within 24 hours of vaccination or the presence of generalized 
urticaria within 72 hours of vaccination in any subject, considered at least possibly related to 
the study vaccine; OR

A life-threatening or other serious adverse event in any subject, considered at least possibly 
related to the study vaccine.
Cohorts 1, 2 and 3
If any of the following events occur in any subject from Cohorts 1, 2 or 3 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:

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

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

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). 

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In case of occurrence of any of the events described above, the sponsor’s medical monitor will 
notify the IDMC immediately. Dosing will be halted and health authorities will be notified. 
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 criteria for pausing will be re-set each time and the 
same criteria have to be met again to halt further vaccination. 
9.4.
Immunogenicity Evaluations
Venous blood samples will be collected for the determination of immune responses at the time 
points indicated in the Time and Events Schedule. Samples for assessment of humoral immune 
responses will be taken from all subjects. Samples for assessment of cellular immunity will be 
taken from subjects at selected sites with the capabilities to process PBMC (targeted at 
165 subjects [138 Ad26.ZEBOV and/or MVA-BN-Filo, and 27 placebo] in Cohort 1 and 
33 subjects [28 Ad26.ZEBOV and/or MVA-BN-Filo, and 5 placebo] in each of the other 
cohorts). Samples to assess cellular immune responses are optional for subjects in the Cohort 1 
substudy and may only be collected in a subset of subjects. Blood volumes are presented in 
Table 7 below.
Sample collection and processing will be performed by the study-site personnel according to 
current versions of approved standard operating procedures. The Laboratory Manual contains 
further details regarding the collection, handling, labeling, and shipment of blood samples to the 
respective laboratories.

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Table 7:
Whole Blood Volumes for Immunogenicity Assessments
Cohort
Humoral Immune 
Response 
(mL)
Cellular Immune 
Response 
(mL)
Approximate Total 
Blood Volume for 
Immunogenicity Assays 
(mL)
1
Healthy adult and elderly 
subjects
10
40
200b/300/350c
Cohort 1 substudy subjects
10
40a
350d/360/400c,d/410c
[430d/480/480c,d/530c]
2a
HIV-infected subjects
10
40
300
2b
Adolescents 
(12-17 years inclusive)
10
20
150
3
Children 
(4-11 years inclusive)
9-, 10- and 11-year old:
5
10
65
6-, 7- and 8-year old:
2.5
6
36.5
4- and 5-year old:
2.5
4
28.5
a These samples are optional and may only be collected in a subset of subjects.
b Only for subjects who do not receive a boost vaccination because of a study pause.
c Subjects in Groups 2 and 3 from Cohort 1 have an extra visit on Day 15, to assess the immune response after 
prime vaccination.
d In case the pre-third vaccination blood sample coincides with the Day 365 blood sample. 
* Approximate total blood volumes including optional PBMC samples.
The immunologic assessments and purposes are summarized in Table 8. The exploratory assay 
package may include, but might not be limited to, the listed assays.
Table 8:
Summary of Immunologic Assessments
Sample
Purpose (non-exhaustive)
Serum, taken 
from all subjects
(N=1,056)
- Analysis of antibodies binding to EBOV GP (ELISA), possibly using different EBOV GPs
- Analysis of neutralizing antibodies to EBOV GP (Virus neutralization assay), possibly 
using different EBOV GPs
- Binding and/or neutralizing antibodies to adenovirus and/or MVA (Adenovirus and/or 
MVA ELISA and/or neutralization assay)
- Analysis of anti-EBOV GP, filovirus GPs and/or TAFV NP antibody characteristics, 
including IgG subtyping (molecular antibody characterization )
- …
PBMC, taken 
from subjects at 
selected sites*
- T-cell IFN-γ responses to EBOV GP (ELISpot)
- Analysis of T-cell responses to EBOV GP, filovirus GPs and/or TAFV NP (including 
CD4/8, IL-2, IFN-γ, TNF-α and/or activation markers) (ICS)
- …
IgG: immunoglobulin G; ICS: intracellular cytokine staining; IFN: interferon; IL: interleukin; TNF: tumor 
necrosis factor
* (targeted at 165 subjects [138 Ad26.ZEBOV and/or MVA-BN-Filo, and 27 placebo] in Cohort 1 and 
33 subjects [28 Ad26.ZEBOV and/or MVA-BN-Filo and 5 placebo] in each of the other cohorts). PBMC 
samples are optional for subjects in the Cohort 1 substudy and may only be collected in a subset of subjects.

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9.5.
Vaccine-induced Seropositivity 
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 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. The potential of a study participant becoming 
PCR-positive after vaccination is being assessed in a Phase 1 study (VAC52150EBL1002).
Subjects should not donate blood during participation in the study (from the start of screening 
onwards; see Sections 4.1.2 and 4.2.3). 
Consent will be obtained to contact the doctors that the subject sees regularly, to let them know 
that the subject is taking part in this study. It is important for all of the subject's doctors to know 
that the subject may be administered experimental vaccines. Subjects participating in the study 
will be provided with a "wallet (study) card" and instructed to carry this card with them for the 
duration of the study (see Section 12.3.1).
9.6.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the CRF or laboratory 
requisition form.
Refer to the Time and Events Schedule for the timing and frequency of all sample collections.
Instructions for the collection, handling, storage, and shipment of samples are found in the 
laboratory manual that will be provided. Collection, handling, storage, and shipment of samples 
must be under the specified, and where applicable, controlled temperature conditions as indicated 
in the laboratory manual.
10.
SUBJECT COMPLETION/DISCONTINUATION OF STUDY 
VACCINE/WITHDRAWAL FROM THE STUDY
10.1.
Completion
A subject will be considered to have completed the study if he or she has completed all 
assessments at the 6-month post-boost vaccination visit or at the Day 365 visit, whichever occurs 
later. A subject in the Cohort 1 substudy will be considered to have completed the study if he or 
she has completed all assessments at the 1-year post third vaccination visit.
10.2.
Discontinuation of Study Vaccine/Withdrawal From the Study
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.

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A subject’s study vaccine (prime or boost) must be discontinued at the discretion of the 
investigator and after consultation with the sponsor for any of the events in Section 6.2.
A subject's study vaccine should be permanently discontinued if:

The investigator believes that for safety reasons (eg, adverse event) it is in the best interest 
of the subject to discontinue study vaccine;

The subject becomes pregnant;

The subject has confirmed Ebola virus disease through natural exposure to the virus (eg, by 
travel to an affected country);

The subject experiences any of the events described in Section 6.3;

The randomization code is broken by the investigator or the study-site personnel. 
Subjects meeting any of the reasons listed above must not receive any further study vaccine, but 
should continue to be monitored for safety and for immunogenicity according to the protocol if 
this does not result in safety risks for the subject. In case of early discontinuation of study 
vaccine due to an adverse event, the investigator will collect all information relevant to the 
adverse event and safety of the subject, and will follow the subject to resolution, or until reaching 
a clinically stable endpoint. In case of a study pause, subjects who were primed prior to the pause 
and did not yet receive a boost vaccination need to follow the visits as described in Table 5. 
Once they receive the late boost vaccination, these subjects need to follow the visits as described 
in Table 4.
Withdrawal From the Study
Each subject has the right to withdraw from the study at any time for whatever reason. 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.
A subject will be withdrawn from the study for any of the following reasons:

Decision by the investigator to withdraw a subject for repeated failure to comply with 
protocol requirements;

Decision by the sponsor to stop or cancel the study;

Decision 
by 
local 
regulatory 
authorities 
and 
Independent 
Ethics 
Committee 
(IEC)/Institutional Review Board (IRB) to stop or cancel the study;

Lost to follow-up;

Withdrawal of consent;

Death.
If a subject withdraws early from the study for any of the reasons listed above (except in case of 
death), early withdrawal assessments should be obtained (ie, physical examination and 

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immunogenicity assessments for serum and PBMCs). 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), but the subject has the right to refuse. 
If a subject is lost to follow-up, every reasonable effort must be made by the study site personnel 
to contact the subject and determine the reason for discontinuation/withdrawal. The measures 
taken to follow up must be documented.
When a subject withdraws before completing the study, the reason for withdrawal is to be 
documented in the CRF and in the source document. Study vaccine assigned to the withdrawn 
subject may not be assigned to another subject. For subjects who withdraw from the study after 
randomization but before the prime vaccination, an additional subject will be enrolled who will 
receive the same vaccination regimen as the withdrawn subject. Subjects who withdraw from the 
study after receiving the prime vaccination will not be replaced.
10.3.
Withdrawal From the Use of Research Samples
A subject who withdraws from the study will have the following options for storage of samples 
for potential future use:

The collected samples will be retained and used in accordance with the subject's original 
informed consent for storage of samples for future use.

The subject may withdraw consent for storage of samples for potential future use (see 
Section 16.2.5), in which case the samples will be destroyed and no further testing will take 
place. To initiate the sample destruction process, the investigator must notify the sponsor 
study site contact of withdrawal of consent for the storage of leftover samples for future 
research and request sample destruction. The sponsor study site contact will, in turn, contact 
the biomarker representative to execute sample destruction. If requested, the investigator 
will receive written confirmation from the sponsor that the samples have been destroyed.
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. Specific details will be provided in the Statistical Analysis Plan (SAP). 
The primary analysis will be conducted when all subjects in Cohort 1 have completed the 
6-month post-boost visit or discontinued earlier, to aid in the assessment of which vaccination 
schedule will be the best candidate for future studies and implementation in the field. Study-site
personnel, subjects and sponsor personnel involved in subject level data review will remain 
blinded until the last subject in that cohort has completed the study. Sponsor personnel involved 
in the conduct of the primary analysis and in making future decisions for the program will be 
unblinded to the data of Cohort 1, but will remain blinded to the data of the other cohorts.
Interim analyses may be performed as described in Section 11.7.

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The final analysis will be performed when all subjects have completed the last study-related visit 
or discontinued earlier (including subjects participating in the Cohort 1 substudy).
A general description of the statistical methods to be used to analyze the safety and 
immunogenicity data is outlined below. 
Details on how to handle the data from subjects with a late boost will be described in the SAP, 
developed before unblinding.
Subjects who are outside the protocol-defined boost vaccination window due to a study pause
and elect not to receive a late boost vaccination will not be replaced.
11.1.
Endpoints
Primary Endpoints
11.1.1.

Adverse events, collected until the 42-day post-last vaccination (excluding third vaccination)
visit.

Serious adverse events and IREs, collected from signing of the ICF onwards until the end of 
the study.

Solicited local and systemic adverse events (reactogenicity), collected until 7 days after each 
study vaccine administration.
Secondary Endpoint
11.1.2.
Humoral immune response

Binding antibody levels elicited by vaccination using EBOV GP ELISA at 21 days post
boost.
Safety and tolerability (Cohort 1 substudy)

Adverse events, collected from the day of the third vaccination onwards until 28 days 
thereafter (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 and IREs, collected from signing of the original ICF onwards until 
the end of the study (including Cohort 1 substudy).

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Exploratory Endpoints
11.1.3.
Additional exploratory analyses may be performed to further investigate study vaccine-elicited 
immune responses. These may include, but might not be limited to, the following assays: 
Humoral immune response

Binding antibody levels elicited by vaccination using EBOV GP ELISA at other relevant 
time points (including Cohort 1 substudy).

Neutralizing antibody responses against the EBOV GP defined as the serum titer that is able 
to inhibit viral infection by a certain percentage (IC50, IC80 and/or IC90) using virus 
neutralization assay. 

Binding and/or neutralizing antibody responses against the Ad26 and/or MVA vector, using 
adenovirus and/or MVA ELISA and/or neutralization assays.

Humoral responses to different EBOV GPs and/or filovirus GPs and/or TAFV NP if assays 
are available.

Molecular characterization of study vaccine-elicited antibodies which may include, but will 
not be limited to: Fc characterization, isotype analysis and epitope mapping.
Cellular immune response

The presence and functional capacity of T cells may be determined using pathogen-specific 
stimulation of PBMC with EBOV GP peptides using IFN-ELISpot assays. Cytokine-
producing T cells can be quantified using ELISpot technology.

Activation of CD4+ and CD8+ T cell subsets and their cytokine expression patterns may be 
determined by flow cytometry after EBOV GP-specific stimulation (including, but not 
limited to, IFN-, interleukin [IL]-2, and tumor necrosis factor [TNF]-) using intracellular 
cytokine staining (ICS). Exploratory phenotypic and functional analysis may be included.

Cellular responses to filovirus GPs and/or TAFV NP if assays are available.
11.2.
Sample Size Determination
An overall planned sample size of 1,056 subjects includes 880 subjects to receive Ad26.ZEBOV 
and MVA-BN-Filo prime-boost vaccination to substantially contribute to an overall safety data 
base of the Ad26.ZEBOV and MVA-BN-Filo prime-boost regimen. 
In Cohort 1, a total of 550 subjects are planned to be vaccinated with Ad26.ZEBOV and 
MVA-BN-Filo across the vaccination schedules (220 in Groups 1 and 2, 110 in Group 3). In the 
other cohorts (2a, 2b, and 3), 55 subjects per vaccination schedule (Groups 1 and 2) are planned 
to be vaccinated with Ad26.ZEBOV and MVA-BN-Filo, or a total of 110 subjects per 
subpopulation.

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The probability of detecting an adverse event in each of the populations, and total, is given in 
Table 9, for various true incidence rates. In case a specific adverse event is not observed, the 
one-sided 97.5% upper confidence limit of the true incidence rate of this adverse event is less 
than 6.5%, 3.3%, 1.7%, 0.8%, 0.7% and 0.5%, for sample sizes of 55, 110, 220, 440, 550 and 
880 subjects, respectively.
Table 9:
Probability of Observing at Least One Adverse Event Given a True Adverse Event Incidence
True Adverse Event 
Incidence (%)
N=55
N=110
N=220
N=440
N=550
N=880
0.1
5%
10%
20%
36%
42%
59%
0.5
24%
42%
67%
89%
94%
99%
1.0
42%
67%
89%
99%
100%
100%
2.5
75%
94%
100%
100%
100%
100%
5.0
94%
100%
100%
100%
100%
100%
10.0
100%
100%
100%
100%
100%
100%
Having immunogenicity data available for 55, 110 or 220 subjects per group on Ad26.ZEBOV or 
MVA-BN-Filo within a cohort, the following pairwise differences in immune response (ELISA 
antibody levels against EBOV GP) between vaccine schedules can be detected at any given time 
point, for a given variability in ELISA antibody levels (Table 10).
Table 10:
Magnitude of Pairwise Difference to be Detected Between Vaccine Regimens for a Given 
Sample Size 
Variability ELISA antibody
levels (SD, log10 scale)
Detectable difference, log10 scale *
n1=n2=55
n3=110, n1,n2=220
n1=n2=220
0.3
0.19
0.13
0.11
0.4
0.25
0.18
0.14
0.5
0.31
0.22
0.18
SD: standard deviation
* 90% power, 5% significant level for 2-sided hypothesis, accounting for multiple testing in Cohort 1
11.3.
Analysis Sets
The Full Analysis set includes all subjects who were randomized and received at least one dose
of study vaccine, regardless of the occurrence of protocol deviations. Safety data will be analyzed 
based on the Full Analysis set.
The Immune Response Analysis set includes all randomized and vaccinated subjects, who have 
data from baseline and at least one post-vaccination immunogenicity blood draw.
The Per Protocol Analysis set for the main study includes all randomized and vaccinated 
subjects, who received both the prime and boost (administered not more than 10 days outside the 
visit window) vaccinations, have immunogenicity data from baseline and at least one post-
vaccination evaluable immunogenicity sample, and have no major protocol violations
influencing the immune response.

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A similar Per Protocol Analysis set will be used for the Cohort 1 substudy for the time points 
after the third vaccination.
The immunogenicity analysis will be based on the Per Protocol Analysis set. As sensitivity 
analysis, the immunogenicity data will also be analyzed based on the Immune Response Analysis 
set, provided more than 10% of subjects in the Immune Response Analysis set are excluded from 
the Per Protocol Analysis set.
Details on how to handle the data from subjects with a late boost will be described in the SAP, 
developed before unblinding.
11.4.
Subject Information
For all subjects, demographic characteristics (eg, age, height, weight, BMI, race, and sex) and 
screening/baseline characteristics (eg, physical examination, medical history) will be tabulated 
and summarized with descriptive statistics.
11.5.
Safety Analyses
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively 
(including 95% confidence intervals, if applicable). 
Similar safety summaries will be created for the subjects who received a third vaccination, 
details will be provided in the SAP.
Baseline for all safety parameters will be defined as the last value before the prime vaccination.
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 after 
vaccination (solicited local, solicited systemic, and unsolicited) will be included in the analysis. 
For each adverse event, the number and percentage of subjects who experience at least one 
occurrence of the given event will be summarized by group. 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 for solicited adverse events will be done on those subjects in the Full Analysis set for 
whom reactogenicity assessments are available in the database. The analysis of unsolicited 
adverse events will be done based on the Full Analysis set. 
Physical Examination
Physical examination abnormalities following vaccination will be tabulated by most severe
abnormality grade. 
For Cohorts 1 and 2, BMI will be calculated using the recording of height at screening. Body 
weight and BMI results will be tabulated and summarized descriptively.

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For Cohort 3, percentiles of weight and height (according to CDC growth charts, see 
Section 4.2.3) will be tabulated and summarized descriptively.
Vital signs 
The percentage of subjects with values beyond clinically important limits will be summarized.
Vital signs abnormalities following vaccination will be tabulated by most severe abnormality 
grade.
Clinical Laboratory Tests
Laboratory abnormalities will be determined according to the toxicity grading tables, and in 
accordance with the normal ranges of the clinical laboratory. The most severe laboratory 
abnormalities following vaccination will be tabulated per regimen.
11.6.
Immunogenicity Analyses
Descriptive statistics (actual values and changes from baseline, including 95% confidence 
intervals, if applicable) will be calculated for continuous immunologic parameters by time point. 
Graphical representations of changes in immunologic parameters will be prepared, as applicable. 
Frequency tabulations will be calculated for discrete (qualitative) immunologic parameters by 
time point. In addition, differences between the vaccination schedules will be described at the 
21-day post-boost, 6-month post-boost, and Day 365 visits. Similar summaries will be provided 
for the time points after the third vaccination for the Cohort 1 substudy population.
Details on the statistical analysis of the immunogenicity data and on the data for subjects who 
received a late boost vaccination will be provided in the SAP.
11.7.
Interim Analyses
For the Cohort 1 substudy of subjects who received the third vaccination, an interim analysis 
may be performed when all subjects have completed the 6-month post third vaccination visit, or 
discontinued earlier. 
In each cohort, after completion of the 6-month post-boost visit by all subjects, an interim 
analysis will be conducted on safety and selected immunogenicity data and the cohort will be 
unblinded to the sponsor.
A separate interim SAP will be prepared before the conduct of an interim analysis.
11.8.
Independent Data Monitoring Committee
An IDMC will be established to monitor data on an ongoing basis to ensure the continuing safety 
of the subjects enrolled in this study. The committee will meet periodically to review interim 
data. Ad hoc IDMC meetings may be requested via the sponsor for any single event or 
combination of multiple events which are considered to jeopardize the safety of the subjects. 
After the review, the IDMC will make recommendations regarding the continuation of the study. 
The details will be provided in a separate IDMC charter.

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The IDMC will be appointed by the sponsor with recommendations from the Clinical Steering 
Committee (see Section 11.9) before the start of the 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, and procedures will be documented in its charter. Any safety 
reports/interim data from the cohorts in this study reviewed by the IDMC and the 
recommendations of the IDMC will be shared with the local health authorities and the 
IECs/IRBs.
11.9.
Trial Management Team and Clinical Steering Committee 
Oversight of the study will be conducted by the Trial Management Team which will consist of 
members from the sponsor as well as key collaborators from participating countries. This Trial 
Management Team will be responsible for protocol development and ensuring proper study 
execution. As part of the consortium agreement between the sponsor, INSERM and the London 
School of Hygiene and Tropical Medicine, a Clinical Steering Committee with representatives 
from each consortium partner has been established to guide the overall clinical development 
plan, including this study. The Clinical Steering Committee is responsible for overseeing the 
EBOVAC2 collaboration activities and for making decisions on specific issues.
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
Adverse Event Definitions and Classifications
12.1.1.
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])
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).

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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 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) by the sponsor to the 
Health Authorities and by the investigator to the IEC/IRB according to regulatory and local 
requirements. 
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An adverse event is considered unlisted if the nature or severity is not consistent with the 
applicable product reference safety information. For Ad26.ZEBOV and MVA-BN-Filo, the 
expectedness of an adverse event will be determined by whether or not it is listed in the 
Investigator's Brochures and Addenda, if applicable.14,15
Adverse Event Associated with the Use of the Study Vaccine
An adverse event is considered associated with the use of the study vaccine if the attribution is 
possibly, probably, or very likely by the definitions listed in Section 12.1.2, Attribution 
Definitions.
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.

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
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.
Attribution Definitions
12.1.2.
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 underlying disease(s), concomitant drug(s). This applies to all adverse 
events, whether serious or non-serious. Assessment of causality must be done by a licensed study 
physician (the investigator or designee).
The investigator will use the following guidelines to assess the causal relationship of an adverse 
event 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.

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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. 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.
Severity Criteria 
12.1.3.
Adverse events and laboratory data will be coded for severity using the toxicity grading tables in
Attachment 2 and Attachment 3. 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. 
12.2.
Special Reporting Situations
Safety events of interest on a sponsor study vaccine that may require expedited reporting or 
safety evaluation include, but are not limited to:

Administration of an overdose of study vaccine 

Accidental or occupational exposure to a study vaccine

Administration error involving a study vaccine (with or without subject/patient exposure to 
the 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.

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12.3.
Procedures
All Adverse Events
12.3.1.
All adverse events and special reporting situations, whether serious or non-serious, will be 
reported from the time a signed and dated ICF/assent is obtained until the 42-day post-last 
vaccination visit (excluding third vaccination), and again from the day of the third vaccination
until 28 days thereafter for subjects in the Cohort 1 substudy. Serious adverse events and IREs
will be collected from signing of the ICF onwards until the end of the study. Subjects will be 
instructed to record solicited local and systemic adverse events (reactogenicity) in the diary in 
the evening after each vaccination and then daily for the next 7 days at approximately the same 
time each day.
Serious adverse events must be reported by the investigator 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 events 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. To ensure 
that all adverse events are captured in a timely manner, the CRF will be entered in real-time and 
subjected to review to identify adverse events which may invoke pausing rules.
The investigator must review both post-injection reactogenicity and other adverse event CRF to 
insure the prompt and complete identification of all events that require expedited reporting as 
serious adverse events, invoke pausing rules or are other serious and unexpected events.
All adverse events, regardless of seriousness, severity, or presumed relationship to study 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. 
Participating investigators and IEC/IRB will receive a blinded SUSAR summary, unless 
otherwise specified.

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For all studies with an outpatient phase, including open-label studies, the subject must be 
provided with a "wallet (study) card" and instructed to carry this card with them for the duration 
of the study indicating the following:

Study number

Statement, in the local language(s), that the subject is participating in a clinical study and 
that results from Ebola virus serological screening tests should be interpreted with caution as 
the subject could have a false positive test (not truly infected with Ebola virus) as a result of 
an immune response to the candidate Ebola vaccine.  

Investigator's name and 24-hour contact telephone number

Local sponsor's name and 24-hour contact telephone number (for medical staff only)

Site number

Subject number

Any other information that is required to do an emergency breaking of the blind
Serious Adverse Events
12.3.2.
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.
Information regarding serious adverse events will be transmitted to the sponsor using the Serious 
Adverse Event Form, which must be completed and signed by a physician from the study site, 
and transmitted to the sponsor within 24 hours. The initial and follow-up reports of a serious 
adverse event should be made by facsimile (fax).
All serious adverse events that have not resolved by the end of the study, or that have not 
resolved upon discontinuation of the subject's participation in the study, must be followed until 
any of the following occurs:

The event resolves

The event stabilizes

The event returns to baseline, if a baseline value/status is available

The event can be attributed to agents other than the study vaccine or to factors unrelated to 
study conduct

It becomes unlikely that any additional information can be obtained (subject or health care 
practitioner refusal to provide additional information, lost to follow-up after demonstration 
of due diligence with follow-up efforts)

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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.
The cause of death of a subject in a study, whether or not the event is expected or associated with 
the study vaccine, is considered a serious adverse event.
Immediate Reportable Events
12.3.3.
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 in Section 12.1.1) 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 serious adverse event criteria (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 
complete IRE Form page 3 to be included as part of the Serious Adverse Event report.
Pregnancy
12.3.4.
Pregnancies will be reported from signing of the ICF until the end of the study.
All initial reports of pregnancy in female subjects or partners of male subjects 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 

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becomes pregnant during the study must be promptly withdrawn from further study vaccination 
but should continue participation in the study for safety follow-up.
Because the effect of the study vaccine on sperm is unknown, pregnancies in partners of male 
subjects included in the study will be reported as noted above.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required to be sent to the sponsor.
The parent(s)/legal guardian of children born to vaccinated female subjects who become 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 placebo), will be approached to consent 
for enrollment of their children into the VAC52150 Vaccine Development Roll-over study (see 
Section 9.1.8).
12.4.
Contacting Sponsor Regarding Safety
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding safety issues or questions regarding the study are listed in the Contact Information 
page(s), which will be provided as a separate document.
13.
PRODUCT QUALITY COMPLAINT HANDLING
A product quality complaint (PQC) is defined as any suspicion of a product defect related to 
manufacturing, labeling, or packaging, ie, any dissatisfaction relative to the identity, quality, 
durability, or reliability of a product, including its labeling or package integrity. A PQC may have 
an impact on the safety and efficacy of the product. Timely, accurate, and complete reporting and 
analysis of PQC information from studies are crucial for the protection of 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.
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 in the Contact Information page(s), which will be 
provided as a separate document.

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14.
STUDY VACCINE INFORMATION
14.1.
Description of Study Vaccines
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 suspension to be thawed before use. Each vial contains 
an extractable volume of 0.5 mL. Refer to the Investigator's Brochure for a list of excipients.14
The Ad26.ZEBOV vaccine is manufactured by IDT Biologika GmbH for Janssen Vaccines & 
Prevention B.V., The Netherlands.
MVA-BN-Filo
MVA-BN-Filo is a recombinant multivalent vaccine intended for active immunization against 
Ebola and Marburg virus infection. MVA-BN-Filo is strongly attenuated; the vaccine is 
propagated in primary chicken embryo fibroblast cells and does not replicate in human cells.
The MVA-BN-Filo vaccine is supplied at a concentration of 2x108 Inf U/mL (nominal titer) in 
2-mL 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.15
The MVA-BN-Filo vaccine is manufactured by IDT Biologika GmbH for Janssen Vaccines & 
Prevention B.V., The Netherlands.
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 on site without prior approval from the 
sponsor.
Further details for study vaccine packaging and labeling can be found in the Site Investigational 
Product Procedures Manual.

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14.3.
Preparation, Handling, and Storage
Study vaccine must be stored at controlled temperatures: Ad26.ZEBOV vials must be stored at 
≤-65C and MVA-BN-Filo vials must be stored at ≤–20C.
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.
Blinding will be achieved by preparation of study vaccine by unblinded qualified study-site 
personnel not involved in any other study-related procedure, and by the administration of vaccine 
in a masked syringe by a blinded study vaccine administrator (see Definitions of Terms).
Details on the preparation, the holding time and storage conditions from the time of preparation 
to administration of Ad26.ZEBOV and MVA-BN-Filo are provided in the Site Investigational 
Product Procedures Manual.
14.4.
Study 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 
study vaccine will be documented on the study vaccine return form. When the study site is an 
authorized destruction unit and study vaccine supplies are destroyed on-site, this must also be 
documented on the study vaccine return form.
Potentially hazardous materials such as used ampules, needles, syringes and vials containing 
hazardous liquids, should be disposed of immediately in a safe manner and therefore will not be 
retained for study vaccine accountability purposes.
Study vaccine should be dispensed under the supervision of the investigator or a qualified 
member of the study-site personnel, or by a qualified staff member. Study vaccine will be 
supplied only to subjects participating in the study. Returned study vaccine must not be 
dispensed again, even to the same subject. Study vaccine may not be relabeled or reassigned for 
use by other subjects. 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.

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15.
STUDY-SPECIFIC MATERIALS
The investigator will be provided with the following supplies:

Investigator’s Brochures and Addenda (if applicable) for Ad26.ZEBOV and MVA-BN-Filo 

Site Investigational Product Procedures Manual

Laboratory Manual

IWRS Manual 

Electronic Data Capture (eDC) Manual/electronic CRF Completion Guidelines and 
Randomization Instructions

Sample ICF

Subject diaries

TOU

Rulers, thermometers

Subject wallet cards

Recruitment tools, as applicable
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 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 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 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 should be 
obtained from children (minors) capable of understanding the nature of the study, typically subjects 
7 years of age and older, depending on the local regulations and practice. 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.

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Approximately 200 to 400 mL of blood (including PBMC samples) will be drawn from adults
and adolescents (12-17 years of age inclusive) over a period of 1 year, and remains well below 
the limits of standard blood donation.
For children (<12 years), the trial-related blood volumes obtained (including any losses during 
phlebotomy) will not exceed 3% of the total blood volume during a period of 4 weeks. In order 
to meet the planned safety, serologic and cellular endpoints, it might be necessary to slightly 
exceed the guideline of 1% of the total blood volume at any single time. The sites will be 
instructed that the procedures should preferably be performed in the following order, according 
to their importance: safety, serology and cellular. The total volume of blood is estimated at 80 to 
90 ml/kg body weight: 3% is 2.4 ml blood per kg body weight.9 The allowable blood volume 
calculations are based on the 10th percentile for growth charts for 4- to 11-year-old children.5
Test of Understanding
The TOU is a short assessment of the subject’s understanding of key aspects of the study
(Attachment 1). 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 after reading but before signing the ICF/assent by all subjects (as 
required per local regulations and practice, see Section 4), prior to enrollment into the study. The 
TOU is reviewed one-on-one with the subject and a member of the study team. Subjects 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.
16.2.
Regulatory Ethics Compliance
Investigator Responsibilities
16.2.1.
The investigator is responsible for ensuring that the study is performed in accordance with the 
protocol, current ICH guidelines on Good Clinical Practice (GCP), and applicable regulatory and 
country-specific requirements.
GCP is an international ethical and scientific quality standard for designing, conducting, 
recording, and reporting studies that involve the participation of human subjects. Compliance 
with this standard provides public assurance that the rights, safety, and well-being of study 
subjects are protected, consistent with the principles that originated in the Declaration of 
Helsinki, and that the study data are credible.

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Independent Ethics Committee or Institutional Review Board
16.2.2.
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

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, unless required locally), the ICF, applicable 
recruiting materials, and subject compensation programs, and the sponsor has received a copy of 
this approval. This approval letter must be dated and must clearly identify the IEC/IRB and the 
documents being approved.
During the study the investigator (or sponsor where required) will send the following documents 
and updates to the IEC/IRB for their review and approval, where appropriate:

Protocol amendments (excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct)

Revision(s) to ICF and any other written materials to be provided to subjects

If applicable, new or revised subject recruiting materials approved by the sponsor

Revisions to compensation for study-related injuries or payment to subjects for participation 
in the study, if applicable

New edition(s) of the Investigator's Brochure and amendments/addenda

Summaries of the status of the 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

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
New information that may adversely affect the safety of the subjects or the conduct of the 
study

Deviations from or changes to the protocol to eliminate immediate hazards to the subjects

Report of deaths of subjects under the investigator's care

Notification if a new investigator is responsible for the study at the site

Development Safety Update Report and Line Listings, where applicable

Any other requirements of the IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct), the amendment and applicable ICF revisions 
must be submitted promptly to the IEC/IRB for review and approval before implementation of 
the change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where 
required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/ IRB 
about the study completion.
Informed Consent and Assent Form
16.2.3.
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) and assent form 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. 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. It also denotes that the subject agrees to 
allow his or her study physician to recontact the subject for the purpose of obtaining consent for 
additional safety evaluations, if needed.

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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.
If the subject or legally acceptable representative is unable to read or write, an impartial witness 
should be present for the entire informed consent process (which includes reading and explaining 
all written information) and should personally date and sign the ICF after the oral consent of the 
subject or legally acceptable representative is obtained.
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 
obtained from children (minors) capable of understanding the nature of the study, typically 
subjects 7 years of age and older, depending on local regulations and practice. Written assent 
should be obtained from subjects who are able to write. A separate assent form written in 
language the subject can understand should be developed for adolescents. After having obtained 
the assent, a copy of the assent form must be given to the subject, and to the subject's parent or if 
applicable legally acceptable representative.
Privacy of Personal Data
16.2.4.
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.
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 immunogenicity 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 

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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.
Long-term Retention of Samples for Additional Future Research 
16.2.5.
Samples collected in this study, for which consent has been obtained and for which additional 
material is available after study-specific testing is complete, may be stored for up to 15 years (or 
according to local regulations) for potential future research. Subjects participating at selected 
sites where PBMC samples are collected will be asked explicitly to consent for potential future 
genetic research to be performed on PBMC samples. Samples will only be used to understand 
Ebola vaccine- and disease-related questions and to develop tests/assays related to the 
characterization of EBOV-directed immune responses or diagnostic tests. The research may 
begin at any time during the study or the post-study storage period.
Stored samples will be coded throughout the sample storage and analysis process and will not be 
labeled with personal identifiers. Subjects may withdraw consent for their samples to be stored 
for potential future research at any time (see Section 10.3, Withdrawal From the Use of Research 
Samples). In such case, their blood samples will be destroyed after all the tests specified for this 
study have been concluded.
The sponsor will be responsible for the overall management of the sample inventory, shipping 
plan, allocation and storage of samples. The sponsor will establish a Material Transfer 
Agreement between all relevant parties (site, sponsor and the central laboratory charged with 
shipment and distribution of the samples). These Material Transfer Agreements will take into 
account national regulations and will be submitted for ethics approval and be in place before a 
site will be activated. Samples will be stored securely at facilities as directed by the sponsor.
Country Selection
16.2.6.
This study will only be conducted in those countries where the intent is to launch or otherwise 
help ensure access to the developed product if the need for the product persists, unless explicitly 
addressed as a specific ethical consideration in Section 16.1, Study-Specific Design 
Considerations.
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 

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sponsor. When the change(s) involve(s) only logistic or administrative aspects of the study, the 
IEC/IRB (where required) only needs to be notified.
During the course of the study, in situations where a departure from the protocol is unavoidable, 
the investigator or other physician in attendance will contact the appropriate sponsor 
representative (listed in the Contact Information page(s), which will be provided as a separate
document). Except in emergency situations, this contact should be made before implementing 
any departure from the protocol. In all cases, contact with the sponsor must be made as soon as 
possible to discuss the situation and agree on an appropriate course of action. The data recorded 
in the CRF and source documents will reflect any departure from the protocol, and the source 
documents will describe this departure and the circumstances requiring it.
17.2.
Regulatory Documentation
Regulatory Approval/Notification
17.2.1.
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities 
in each respective country, if applicable. A study may not be initiated until all local regulatory 
requirements are met.
Required Prestudy Documentation
17.2.2.
The following documents must be provided to the sponsor before shipment of study vaccine to 
the study site:

Protocol and amendment(s), if any, signed and dated by the principal investigator

A copy of the dated and signed (or sealed, where appropriate per local regulations), written 
IEC/IRB approval of the protocol, amendments, ICF, any recruiting materials, and if 
applicable, 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.

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
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. In cases where the subject is not randomized into the study, the date seen and 
date of birth will be used.
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.
17.4.
Source Documentation
At a minimum, source documents consistent in the type and level of detail with that commonly 
recorded at the study site as a basis for standard medical care, must be available for the 
following: subject identification, eligibility, and study identification; study discussion and date of 
signed informed consent; dates of visits; results of safety and immunogenicity parameters as 
required by the protocol; record of all adverse events and follow-up of adverse events; 
concomitant medication; study 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. The author of an entry in the source 
documents should be identifiable.
Specific details required as source data for the study and source data collection methods will be 
reviewed with the investigator before the study and will be described in the monitoring 
guidelines (or other equivalent document).
The information contained in the subject diary is primary data. Either the physical diary or diary 
information collected in the subject’s medical record will be considered a source document. 
Information from the diary provided to subjects to record solicited local and systemic adverse 

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events until 7 days after each vaccination, will be reviewed by the investigator or designee to 
transcribe into the relevant parts of the CRF as described in the CRF Completion Guidelines.
17.5.
Case Report Form Completion
Case report forms are prepared and provided by the sponsor for each subject in electronic format.
All CRF entries, corrections, and alterations must be made by the investigator or authorized 
study-site personnel. The investigator must verify that all data entries in the CRF are accurate 
and correct.
The study data will be transcribed by study-site personnel from the source documents onto an 
electronic CRF, if applicable. Study-specific data will be transmitted in a secure manner to the 
sponsor.
Data must be entered into the CRF in English. The CRF must be completed as soon as possible 
after a subject visit and the forms should be available for review at the next scheduled 
monitoring visit.
If necessary, queries will be generated in the eDC tool. If corrections to a CRF are needed after 
the initial entry into the CRF, this can be done in either of the following ways:

Investigator and study-site personnel can make corrections in the eDC tool at their own 
initiative or as a response to an auto query (generated by the eDC tool).

Sponsor or sponsor delegate can generate a query for resolution by the investigator and 
study-site personnel.
17.6.
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 CRF for accuracy and completeness during on-site 
monitoring visits and after transmission to the sponsor; any discrepancies will be resolved with 
the investigator or designee, as appropriate. After upload of the data into the study database they 
will be verified for accuracy and consistency with the data sources.
17.7.
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all CRF 
and all source documents that support the data collected from each subject, as well as all study 
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a 
Clinical Trial, and all study documents as specified by the applicable regulatory requirement(s). 
The investigator/institution will take measures to prevent accidental or premature destruction of 
these documents.

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Essential documents must be retained until at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. These documents will be 
retained for a longer period if required by the applicable regulatory requirements or by an 
agreement with the sponsor. It is the responsibility of the sponsor to inform the 
investigator/institution as to when these documents no longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who will 
accept the responsibility. The sponsor must be notified in writing of the name and address of the 
new custodian. Under no circumstance shall the investigator relocate or dispose of any study 
documents before having obtained written approval from the sponsor.
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any 
documentation relating to this study, the investigator/institution must permit access to such 
reports.
17.8.
Monitoring
The sponsor will perform on-site monitoring visits as frequently as necessary. The monitor will 
record dates of the visits in a study site visit log that will be kept at the study site. The first 
post-initiation visit will be made as soon as possible after enrollment has begun. At these visits, 
the monitor will compare the data entered into the CRF with the source documents (eg, 
hospital/clinic/physician’s office medical records). The nature and location of all source 
documents will be identified to ensure that all sources of original data required to complete the 
CRF are known to the sponsor and study-site personnel and are accessible for verification by the 
sponsor study-site contact. If electronic records are maintained at the study site, the method of 
verification must be discussed with the study-site personnel.
Direct access to source documents (medical records) must be allowed for the purpose of 
verifying that the recorded data are consistent with the original source data. Findings from this 
review will be discussed with the study-site personnel. The sponsor expects that, during 
monitoring visits, the relevant study-site personnel will be available, the source documents will 
be accessible, and a suitable environment will be provided for review of study-related 
documents. The monitor will meet with the investigator on a regular basis during the study to 
provide feedback on the study conduct.
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.

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17.9.
Study Completion/Termination
Study Completion/End of Study
17.9.1.
The study is considered completed with the last visit for the last subject participating in the 
study. The final data from the study site will be sent to the sponsor (or designee) after completion 
of the final subject visit at that study site, in the time frame specified in the Clinical Trial 
Agreement.
Study Termination
17.9.2.
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. 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.
The sponsor representatives (ie, auditors) may use an electronic tool to access your Protected 
Health Information remotely. This electronic tool provides a secure electronic gateway between 
the doctor’s computer and the computer of the sponsor representatives and ensures that nobody 
else will be able to access the information that is being transmitted. This secure electronic 
gateway will only be opened for a limited timeframe after which it will be closed and all contents 
will be deleted.
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 

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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.
The investigator understands that the information developed in the study will be used by the 
sponsor in connection with the continued development of Ad26.ZEBOV and MVA-BN-Filo, and 
thus may be disclosed as required to other clinical investigators or regulatory agencies. To permit 
the information derived from the clinical studies to be used, the investigator is obligated to 
provide the sponsor with all data obtained in the study.
The results of the study will be reported in a Clinical Study Report generated by the sponsor and 
will contain data from all study sites that participated in the study as per protocol. Recruitment 
performance or specific expertise related to the nature and the key assessment parameters of the 
study will be used to determine a coordinating investigator. 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 substudy 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 

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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 disclose the existence of and the results of clinical studies as 
required by law.

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REFERENCES
1.
Baden LR, Liu J, Li H, et al. Induction of HIV-1-specific mucosal immune responses following intramuscular 
recombinant adenovirus serotype 26 HIV-1 vaccination of humans. J Infect Dis. 2015;211(4):518-528.
2.
Baden LR, Walsh SR, Seaman MS, et al. First-in-human evaluation of the safety and immunogenicity of a 
recombinant adenovirus serotype 26 HIV-1 Env vaccine (IPCAVD 001). J Infect Dis. 2013;207:240-247.
3.
Baize S, Pannetier D, Oestereich L, et al. Emergence of Zaire Ebola virus disease in Guinea. N Engl J Med. 
2014;371(15):1418-1425.
4.
Barouch DH, Liu J, Peter L, et al. Characterization of humoral and cellular immune responses elicited by a 
recombinant adenovirus serotype 26 HIV-1 Env vaccine in healthy adults (IPCAVD 001). J Infect Dis. 
2013;207:248-256.
5.
Centers for Disease Control and Prevention. Clinical Growth Chart. Available at:
htttp://www.cdc.gov/growthcharts/clinical_charts.htm. Accessed 10 March 2015.
6.
Clinical Study Report MAL-V-A001. A Phase I/IIa, double-blind, randomized, placebo-controlled, 
dose-escalation clinical study evaluating safety, tolerability and immunogenicity of two dose levels of 
recombinant adenoviral serotype Ad35 and serotype Ad26 vectors expressing the malaria Plasmodium 
falciparum circumsporozoite antigen administered as heterologous prime-boost regimen, and assessing 
protective efficacy of the higher dose in a malaria challenge model in unblinded conditions. Crucell 
Holland B.V. (Aug 2014).
7.
Clinical Study Report POX-MVA-013. A randomized, double-blind, placebo-controlled Phase III trial to 
evaluate immunogenicity and safety of three consecutive production lots of IMVAMUNE® (MVA-BN®) 
smallpox vaccine in healthy, Vaccinia-naïve subjects. Bavarian Nordic (Aug 2015).
8.
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.
9.
Ethical considerations for clinical trials on medicinal products conducted with the pediatric population: 
Recommendations of the Ad hoc group for the development of implementing guidelines for Directive 
2001/20/EC relating to good clinical practice in the conduct of clinical trials on medicinal products for human 
use. 2008.
10.
Frey SE, Newman FK, Kennedy JS, et al. Clinical and immunologic responses to multiple doses of 
IMVAMUNE (Modified Vaccinia Ankara) followed by Dryvax challenge. Vaccine. 2007;25(51):8562-8573.
11.
Friedrich B, Trefry J, Biggins J, et al. Potential vaccines and post-exposure treatments for filovirus infections. 
Viruses. 2012;4(9):1619-1650.
12.
Geisbert TW, Bausch DG, Feldmann H. Prospects for immunisation against Marburg and Ebola viruses. Rev 
Med Virol. 2010;20(6):344-357.
13.
IMVANEX suspension for injection. UK Summary of Product Characteristics. Available at: 
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002596/human_med_0016
66.jsp&mid=WC0b01ac058001d124. Accessed 24 March 2015.
14.
Investigator’s Brochure: JNJ-61210474 (Ad26.ZEBOV), Edition 2. Crucell Holland B.V. (Feb 2015). For 
updated information, refer to Edition 4 (23 June 2016) and Addendum 1 to Edition 4 (30 August 2016).
15.
Investigator’s Brochure: MVA-BN-Filo (MVA-mBN226B), Edition 5. Bavarian Nordic A/S (Mar 2015). For 
updated information, refer to Edition 10 (11 July 2016).
16.
Investigator’s Brochure: Ad26.ENVA.01 HIV-1 Vaccine, Edition 3. Crucell Holland B.V. (June 2013).
17.
Investigator’s Brochure: JNJ-55471468-AAA, JNJ-55471494-AAA, JNJ-55471520-AAA (Ad26.Mos.HIV) 
HIV 1 vaccine, Edition 2. Crucell Holland B.V. (Nov 2014).
18.
Investigator’s Brochure: JNJ-55471468-AAA, JNJ-55471494-AAA, JNJ-55471520-AAA (Ad26.Mos.HIV) 
HIV 1 vaccine, Addendum to Edition 2. Crucell Holland B.V. (Dec 2014).

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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19.
Jones SM, Feldmann H, Ströher U, et al. Live attenuated recombinant vaccine protects nonhuman primates 
against Ebola and Marburg viruses. Nat Med. 2005;11(7):786-790.
20.
Karita E, Mutua G, Bekker LG, et al. Safety in a Phase 1 randomized, double-blind, placebo-controlled trial 
evaluating two adenovirus hiv vaccines in three different geographic regions (IAVI-B003/IPCAVD-
004/HVTN091 trial). Poster presented at AIDS Vaccine 2013.
21.
MVA-BN® (Modified Vaccinia Ankara - Bavarian Nordic). Available at: http://id.bavarian-
nordic.com/pipeline/technology-platform/mva-bn.aspx. Accessed 24 March 2015.
22.
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.
23.
Sarwar UN, Costner P, Enama ME, et al. Safety and immunogenicity of DNA vaccines encoding ebolavirus 
and marburgvirus wild type glycoproteins in a phase I clinical trial. J Infect Dis. 2015;211(4):549-557.
24.
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.
25.
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(16):2623-2632.
26.
Vollmar J, Arndtz N, Eckl KM, et al. Safety and immunogenicity of IMVAMUNE, a promising candidate as 
a third generation smallpox vaccine. Vaccine. 2006;24(12):2065-2070.
27.
WHO Child Growth Standards (birth to 24 months). Available at: http://www.who.int/childgrowth/en. 
Accessed 10 March 2015.
28.
WHO Fact Sheet No103 Ebola Virus Disease 2014. Available at: 
http://www.who.int/mediacentre/factsheets/fs103/en/. Accessed 26 February 2015.

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ATTACHMENTS
Attachment 1:
Test of Understanding (TOU)
Note: A culturally appropriate translation will be made available to participating subjects.
Please read each question and answer whether the statement is True or False.
True
  
False
  
1.
The vaccines you will receive in this study will definitely protect against Ebola.
True
  
False
  
2.
Depending on which group you are randomized to, you will need to come to the clinic 
for 7 to up to 12 visits, excluding the screening period, over the next months.
True
  
False
  
3.
The vaccines in this study can give you Ebola.
True
  
False
  
4.
One purpose of this study is to determine if these vaccines are safe to administer to 
humans.
True
  
False
  
5.
Participants in this study will need to avoid engaging in activities that may expose them 
to Ebola virus.
True
  
False
  
6.
You may take other experimental (test) products while you are taking part in this study.
True
  
False
  
7.
You may withdraw from the study at any time if you choose.
True
  
False
  
8.
Women participating in this study are permitted to become pregnant during the study.
True
  
False
  
9.
A participant in this study may experience side effects after vaccination.
True
  
False
  
10. Some participants in this study may develop a positive Ebola test result, despite the fact 
that they do not have Ebola disease.

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Attachment 2:
Toxicity Tables for Use in Trials Enrolling Healthy Adults
The abbreviations used in the following tables are:
ALT: alanine aminotransferase; aPTT: activated partial thromboplastin time; AST: aspartate aminotransferase; AV block: atrioventricular block; bpm: beats per minute; 
CK: creatine kinase; FEV1: forced expiratory volume in 1 second; g: gram; HI: high; HPF: high power field; INR: international normalized ratio; IV: intravenous; LO: 
low; mEq: milliequivalent; mm Hg: millimeter of mercury; N: not graded; PT: prothrombin time; PTT: partial thromboplastin time; QTc: QT-interval corrected for heart 
rate; QTcB: Bazett’s corrected QT interval; QTcF: Fridericia’s corrected QT interval; RBC: red blood cell; Rx: therapy; ULN: upper limit of normal
CLINICAL ADVERSE EVENTS
Grading scale used for clinical adverse events is adapted from the Division of Microbiology and Infectious Diseases (DMID) Toxicity Tables (2014). For adverse events 
not included in the tables below, refer to the severity criteria guidelines in Section 12.1.3.
Cardiovascular
Grade 1
Grade 2
Grade 3
Arrhythmia
Asymptomatic, transient signs, no Rx 
required 
Recurrent/persistent; symptomatic Rx 
required 
Hemorrhage, blood loss 
Estimated blood loss ≤100 mL 
Estimated blood loss >100 mL, no 
transfusion required
Transfusion required
QTcF (Fridericia’s correction) a or 
QTcB (Bazett’s correction)
Asymptomatic, QTc interval 
450-479 ms, OR
Increase in interval <30 ms above 
baseline
Asymptomatic, QTc interval 
480-499 ms, OR
Increase in interval 30-60 ms above 
baselineb
Asymptomatic, QTc interval ≥500 ms, 
OR
Increase in interval ≥60 ms above 
baseline
PR interval (prolonged)
PR interval 0.21-0.25 s
PR interval >0.25 s
Type II 2nd degree AV block OR
Ventricular pause >3.0 s
Respiratory
Grade 1
Grade 2
Grade 3
Cough
Transient; no treatment 
Persistent cough 
Interferes with daily activities
Bronchospasm, acute
Transient; no treatment; 
FEV1 71%-80% of peak flow 
Requires treatment; normalizes with 
bronchodilator; 
FEV1 60%-70% (of peak flow) 
No normalization with bronchodilator; 
FEV1 <60% of peak flow
Dyspnea
Does not interfere with usual and social 
activities
Interferes with usual and social 
activities, no treatment
Prevents daily and usual social 
activity or requires treatment
                                                
a Inclusion dependent upon protocol requirements.
b The Grade 2 increase in interval is changed from 30-50 ms to 30-60 ms since the original DMID Toxicity Tables (2014) did not cover the increase in interval between 
50 and 60 ms.

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Gastrointestinal
Grade 1
Grade 2
Grade 3
Nausea/vomiting
Minimal symptoms; caused minimal 
or no interference with work, school 
or self-care activities
Notable symptoms; required 
modification in activity or use of 
medications; did not result in loss of 
work or cancellation of social activities
Incapacitating symptoms; required bed 
rest and/or resulted in loss of work or 
cancellation of social activities
Diarrhea 
2-3 loose or watery stools or 
<400 g/24 hours
4-5 loose or watery stools or 
400-800 g/24 hours
6 or more loose or watery stools or 
>800 g/24 hours or requires IV hydration
Reactogenicity
Grade 1
Grade 2
Grade 3
Local reactions
Pain/tenderness at injection site
Aware of symptoms but easily 
tolerated; does not interfere with 
activity; discomfort only to touch
Notable symptoms; required 
modification in activity or use of 
medications; discomfort with movement
Incapacitating symptoms; inability to do 
work or usual activities; significant 
discomfort at rest
Erythema/rednessa
2.5-5 cm
5.1-10 cm
>10 cm
Induration/swellingb
2.5-5 cm and does not interfere with 
activity
5.1-10 cm or interferes with activity
>10 cm or prevents daily activity
Itching at the injection site
Minimal symptoms; caused minimal 
or no interference with work, school 
or self-care activities
Notable symptoms; required 
modification in activity or use of 
medications; did not result in loss of 
work or cancellation of social activities
Incapacitating symptoms; required bed 
rest and/or resulted in loss of work or 
cancellation of social activities
Systemic reactions
Allergic reaction 
Pruritus without rash 
Localized urticaria 
Generalized urticaria; angioedema or 
anaphylaxis 
Headache 
Minimal symptoms; caused minimal 
or no interference with work, school 
or self-care activities
Notable symptoms; required 
modification in activity or use of 
medications; did not result in loss of 
work or cancellation of social activities
Incapacitating symptoms; required bed 
rest and/or resulted in loss of work or 
cancellation of social activities
Fatigue/malaise 
Minimal symptoms; caused minimal 
or no interference with work, school 
or self-care activities
Notable symptoms; required 
modification in activity or use of 
medications; did not result in loss of 
work or cancellation of social activities
Incapacitating symptoms; required bed 
rest and/or resulted in loss of work or 
cancellation of social activities
Myalgia
Minimal symptoms; caused minimal 
or no interference with work, school 
or self-care activities
Notable symptoms; required 
modification in activity or use of 
medications; did not result in loss of 
work or cancellation of social activities
Incapacitating symptoms; required bed 
rest and/or resulted in loss of work or 
cancellation of social activities
                                                
a In addition to grading the measured local reaction at the greatest single diameter, the measurement should be recorded as a continuous variable. 
b Induration/swelling should be evaluated and graded using the functional scale as well as the actual measurement. 

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Arthralgia
Minimal symptoms; caused minimal 
or no interference with work, school 
or self-care activities
Notable symptoms; required 
modification in activity or use of 
medications; did not result in loss of 
work or cancellation of social activities
Incapacitating symptoms; required bed 
rest and/or resulted in loss of work or 
cancellation of social activities
Chills
Minimal symptoms; caused minimal
or no interference with work, school 
or self-care activities
Notable symptoms; required 
modification in activity or use of 
medications; did not result in loss of 
work or cancellation of social activities
Incapacitating symptoms; required bed 
rest and/or resulted in loss of work or 
cancellation of social activities
LABORATORY TOXICITY GRADING
Grading scale used for lab assessments is based on ‘FDA’s Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine 
Clinical Trials’, but grade 3 and 4 are pooled below, consistent with the 3 scale toxicity grading used throughout the protocol. If a laboratory value falls within the 
grading as specified below but also within the local laboratory normal limits, the value is considered as normal. For hemoglobin only the change from reference is used 
for the grading. The FDA table does not include toxicity grading for hematocrit, RBC counts or INR. 
Blood, Serum, or Plasma Chemistriesa
LO/HI/N b
Mild 
(Grade 1) 
Moderate 
(Grade 2)
Severe 
(Grade 3)
Sodium (mEq/L or mmol/L)
LO
132-134
130-131
≤129
HI
144-145
146-147
≥148
Potassium (mEq/L or mmol/L)
LO
3.5-3.6
3.3-3.4
≤3.2
HI
5.1-5.2
5.3-5.4
≥5.5
Glucose (mg/dL)
LO
65-69
55-64
≤54
HI c
100-110
111-125
>125
HI d
110-125
126-200
>200
Blood urea nitrogen 
HI
23-26 (mg/dL) or
8.3-9.4 (mmol/L)
27-31 (mg/dL) or
9.5- 11.2 (mmol/L) 
>31 (mg/dL) or
>11.2 (mmol/L)
Creatinine 
N
1.5-1.7 (mg/dL) or
133-151 (µmol/L)
1.8-2.0 (mg/dL) or
152-177 (µmol/L)
>2.0 (mg/dL) or
> 177 (µmol/L)
Calcium (mg/dL)
LO
8.0-8.4
7.5-7.9
<7.5
HI
10.5-11.0
11.1-11.5
>11.5
Magnesium (mg/dL)
LO
1.3-1.5
1.1-1.2
<1.1
Phosphorus (mg/dL)
LO
2.3-2.5
2.0-2.2
<2.0
CK (mg/dL) 
N
1.25-1.5 x ULN
1.6-3.0 x ULN
≥3.1 x ULN
                                                
a Depending upon the laboratory used, reference ranges, eligibility ranges and grading may be split out by sex and/or age.
b Low, High, Not Graded.
c Fasting.
d Non-fasting.

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Blood, Serum, or Plasma Chemistriesa
LO/HI/N b
Mild 
(Grade 1) 
Moderate 
(Grade 2)
Severe 
(Grade 3)
Albumin (g/dL)
LO
2.8-3.1
2.5-2.7
<2.5
Total protein (g/dL)
LO
5.5-6.0
5.0-5.4
<5.0
Alkaline phosphatase (U/L)
N
1.1-2 x ULN
2.1-3 x ULN
>3 x ULN
AST (U/L)
HI
1.1-2.5 x ULN
2.6-5 x ULN
>5 x ULN
ALT (U/L)
HI
1.1-2.5 x ULN
2.6-5 x ULN
>5 x ULN
Bilirubin, serum total (mg/dL) – when accompanied by any 
increase in Liver Function Test 
1.1–1.25 x ULN
1.2 –1.5 x ULN
>1.5 x ULN
Bilirubin, serum total (mg/dL) – when Liver Function Test is 
normal
1.1–1.5 x ULN
1.6–2.0 x ULN
>2.0 x ULN
Amylase (U/L)
N
1.1-1.5 x ULN
1.6-2.0 x ULN
>2.0 x ULN
Lipase (U/L)
N
1.1-1.5 x ULN
1.6-2.0 x ULN
>2.0 x ULN
-
Hematology
LO/HI/N a
Mild 
(Grade 1)
Moderate 
(Grade 2)
Severe 
(Grade 3)
Hemoglobin (women) change from baseline (g/dL)
Hemoglobin (men) change from baseline (g/dL)
LO
Any decrease-1.5
1.6-2.0
>2.0
LO
Any decrease-1.5
1.6-2.0
>2.0
White blood cell count (cell/mm3)
HI
10,800-15,000
15,001-20,000
>20,000
LO
2,500-3,500
1,500-2,499
<1,500
Lymphocytes (cell/mm3)
LO
750-1,000
500-749
< 500
Neutrophils (cell/mm3)
LO
1,500-2,000
1,000-1,499
< 1000
Eosinophils (cell/mm3)
HI
650-1500
1501-5000
> 5000
Platelets (cell/mm3)
LO
125,000-140,000
100,000-124,000
<100,000
Coagulation
PT (seconds)
HI
1.0-1.10 x ULN
1.11-1.20 x ULN
>1.20 x ULN
International Normalized Ratio (INR)b
HI
1.1-1.5 x ULN
1.6-2.0 x ULN
>2.0 x ULN
PTT or aPTT (seconds)
HI
1.0-1.2 x ULN
1.21-1.4 x ULN
>1.4 x ULN
Fibrinogen (mg/dL)
HI
400-500
501-600
>600
LO
150-200
125-149
<125 
Urine 
Protein (dipstick)
HI
Trace
1+
2+
Glucose (dipstick)
HI
Trace
1+
2+
Blood (microscopic) - red blood cells per high power field 
(RBC/HPF)
HI
1-10
11-50 
>50 and/or gross blood
                                                
a Low, High, Not Graded.
b For INR, the values in the table are based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, 2009.

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VITAL SIGNS TOXICITY GRADING
Grading scale used for vital signs is according to DMID Toxicity Tables (2014)
Vital Signs
LO/HI/N a
Mild 
(Grade 1) b
Moderate 
(Grade 2)
Severe 
(Grade 3)
Fever (°C)c
HI
38.0-38.4
38.5-38.9
>38.9
Fever (°F)
HI
100.4-101.1
101.2-102.0
>102.0
Tachycardia 
HI
101-115 bpm
116-130 bpm
>130 bpm or ventricular 
dysrhythmias
Bradycardia 
LO
50-54 or 45-50 bpm 
if baseline <60 bpm
45-49 or 40-44 bpm
if baseline <60 bpm
<45 or <40 bpm 
if baseline <60 bpm
Hypertension (systolic) - mm Hgd
HI
141-150
151-160
>160
Hypertension (diastolic) - mm Hg
HI
91-95
96-100
>100
Hypotension (systolic) - mm Hg
LO
85-89
80-84
<80
Tachypnea - breaths per minute
HI
23-25
26-30
>30
                                                
a Low, High, Not Graded.
b If initial bound of grade 1 has gap from reference range or eligibility range, calculations based on the New England Journal of Medicine (NEJM) reference ranges.
c Axillary temperature. A protocol should select either °C or °F for inclusion.
d Assuming subject is awake, resting, and supine; for adverse events, 3 measurements on the same arm with concordant results.

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Status: Approved, Date: 4 May 2017
Attachment 3:
Toxicity Tables for Use in Trials Enrolling Children Greater Than 3 Months of Age
The abbreviations used in the following tables are:
ALT: alanine aminotransferase; AST: aspartate aminotransferase; CNS: central nervous system; CK: creatine kinase; hpf: high power field; GGT: gamma 
glutamyltransferase; mEq: milliequivalent; PT: prothrombin time; PTT: partial prothrombin time; ULN: upper limit of normal 
CLINICAL ADVERSE EVENTS
Grading scale used for clinical adverse events is adapted from the DMID Pediatric Toxicity Tables for Children Greater Than 3 Months of Age (2007). For adverse 
events not included in the tables below, refer to the severity criteria guidelines in Section 12.1.3.
Gastrointestinal
Grade 1
Grade 2
Grade 3
Nausea/vomiting
Minimal symptoms; caused minimal or no 
interference with work, school or self-care 
activities
Notable symptoms; required modification 
in activity or use of medications; did not 
result in loss of work or cancellation of 
social activities
Incapacitating symptoms; required bed 
rest and/or resulted in loss of work or 
cancellation of social activities
Diarrhea
Slight change in consistency and/or 
frequency of stools
Liquid stools
Liquid stools greater than 4x the 
amount or number normal for the child
Appetite
-
Decreased appetite
Appetite very decreased, no solid food 
taken
Abdominal Pain
Mild
Moderate; no treatment needed
Moderate; treatment needed
Constipation
Slight change in consistency/frequency of 
stool
Hard, dry stools with a change in 
frequency
Abdominal pain
Reactogenicity
Grade 1
Grade 2
Grade 3
Local reactions
Pain/tenderness at injection site
Aware of symptoms but easily tolerated; 
does not interfere with activity; discomfort 
only to touch
Notable symptoms; required modification 
in activity or use of medications; 
discomfort with movement
Incapacitating symptoms; inability to 
do work or usual activities; significant 
discomfort at rest
Erythema/redness
< 10 mm
10-25 mm
26-50 mm
Induration/swelling
< 10 mm
10-25 mm
26-50 mm
Itching at the injection site
Infrequent, brief episode of scratching, 
easily distracted from scratching
Frequent, longer episodes of scratching, 
difficult to distract
Near constant scratching, or scratching 
during sleep; excoriation of skin
Edema
< 10 mm
10-25 mm
26-50 mm
Rash at the injection site
< 10 mm
10-25 mm
26-50 mm
Systemic reactions
Allergic reaction
Pruritus without rash
Pruritic rash
Mild urticaria

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
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Status: Approved, Date: 4 May 2017
Headache
Minimal symptoms; caused minimal or no 
interference with work, school or self-care 
activities
Notable symptoms; required modification 
in activity or use of medications; did not 
result in loss of work/school or 
cancellation of social activities
Incapacitating symptoms; required bed 
rest and/or resulted in loss of 
work/school or cancellation of social 
activities
Fatigue/malaise 
Minimal symptoms; caused minimal or no 
interference with work, school or self-care 
activities
Notable symptoms; required modification 
in activity or use of medications; did not 
result in loss of work/school or 
cancellation of social activities
Incapacitating symptoms; required bed 
rest and/or resulted in loss of 
work/school or cancellation of social 
activities
Myalgia
Minimal symptoms; caused minimal or no 
interference with work, school or self-care 
activities
Notable symptoms; required modification 
in activity or use of medications; did not 
result in loss of work/school or 
cancellation of social activities
Incapacitating symptoms; required bed 
rest and/or resulted in loss of 
work/school or cancellation of social 
activities
Arthralgia
Minimal symptoms; caused minimal or no 
interference with work, school or self-care 
activities
Notable symptoms; required modification 
in activity or use of medications; did not 
result in loss of work/school or 
cancellation of social activities
Incapacitating symptoms; required bed 
rest and/or resulted in loss of 
work/school or cancellation of social 
activities
Chills
Minimal symptoms; caused minimal or no 
interference with work, school or self-care 
activities
Notable symptoms; required modification 
in activity or use of medications; did not 
result in loss of work/school or 
cancellation of social activities
Incapacitating symptoms; required bed 
rest and/or resulted in loss of 
work/school or cancellation of social 
activities
Central Nervous System 
(CNS)
Grade 1
Grade 2
Grade 3
Generalized CNS Symptoms
Dizziness
Level of activity
Slightly irritable OR slightly subdued
Very irritable OR lethargic
Visual
Blurriness, diplopia, or horizontal
nystagmus of <1 hour duration, with 
spontaneous resolution
More than 1 episode of Grade 2 
symptoms per week, or an episode of 
Grade 2 symptoms lasting more than 
1 hour with spontaneous resolution by 
4 hours, or vertical nystagmus
Myelopathy
None
None
Peripheral Nervous System
Grade 1
Grade 2
Grade 3
Neuropathy/Lower Motor 
Neuropathy
Mild transient paresthesia only
Persistent or progressive paresthias, 
burning sensation in feet, or mild 
dyesthesia; no weakness; mild to 
moderate deep tendon reflex changes; 
no sensory loss
Myopathy or Neuromuscular 
Junction Impairment
Normal or mild (<2 x ULN) CK elevation
Mild proximal weakness and/or atrophy 
not affecting gross motor function. Mild 
myalgias with/without mild CK elevation 
(<2 x ULN)
Proximal muscle weakness and/or 
atrophy affecting motor function 
with/without CK elevation; or severe 
myalgias with CK>2 x ULN

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
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Status: Approved, Date: 4 May 2017
Other
Grade 1
Grade 2
Grade 3
Fever 
38.0-38.4 °C or 100.4-101.1 °F
38.5-40 °C or 101.2-104.0 °F
Greater than 40 °C or 104.0 °F
Cutaneous
Localized rash
Diffuse maculopapular rash
Generalized urticaria
Stomatitis
Mild discomfort
Painful, difficulty swallowing, but able to 
eat and drink
Painful: unable to swallow solids
Clinical symptom not otherwise 
specified in this table
No therapy; monitor condition
May require minimal intervention and 
monitoring
Requires medical care and possible 
hospitalization
Laboratory values not otherwise 
specified in this table
Abnormal, but requiring no immediate 
intervention; monitor
Sufficiently abnormal to require 
evaluation as to causality and perhaps 
mild therapeutic intervention, but not of 
sufficient severity to warrant immediate 
changes in study vaccine
Sufficiently severe to require evaluation 
and treatment, including at least 
temporary suspension of study vaccine
LABORATORY TOXICITY GRADING
Serum chemistry
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Bilirubin (when accompanied 
by any increase in other liver 
tests)
1.1-<1.25 x ULN
1.25-<1.5 x ULN
1.5-1.75 x ULN
Bilirubin (when other liver 
function tests are in normal 
range)
1.1-<1.5 x ULN
1.5-<2.0 x ULN
2.0-3.0 x ULN
AST
1.1-<2.0 x ULN
2.0-<3.0 x ULN
3.0-8.0 x ULN
ALT
1.1-<2.0 x ULN
2.0-<3.0 x ULN
3.0-8.0 x ULN
GGT
1.1-<2.0 x ULN
2.0-<3.0 x ULN
3.0-8.0 x ULN
Pancreatic amylase
1.1-1.4 x ULN
1.5-1.9 x ULN
2.0-3.0 x ULN
Uric acid
7.5-9.9 mg/dL
10-12.4 mg/dL
12.5-15.0 mg/dL
CK
See Neuromuscular Toxicity
Creatinine 3 months – 2 years of 
age
0.6-0.8 x ULN
0.9-1.1 x ULN
1.2-1.5 x ULN
Creatinine 2 – 12 years of age
0.7-1.0 x ULN
1.1-1.6 x ULN
1.7-2.0 x ULN
Creatinine greater than 12 years 
of age
1.0-1.7 x ULN
1.8-2.4 x ULN
2.5-3.5 x ULN
Hypernatremia
-
<145-149 mEq/L
150-155 mEq/L
Hyponatremia
-
130-135 mEq/L
129-124 mEq/L
Hyperkalemia
5.0-5.9 mEq/L
6.0-6.4 mEq/L
6.5-7.0 mEq/L
Hypokalemia
3.0-3.5 mEq/L
2.5-2.9 mEq/L
2.0-2.4 mEq/L
Hypercalcemia
10.5-11.2 mg/dL
0.9-1.1 mg/dL
12.0-12.9 mg/dL
Hypocalcemia
7.8-8.4 mg/dL
7.0-7.7 mg/dL
6.0-6.9 mg/dL

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
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Status: Approved, Date: 4 May 2017
Hypomagnesemia
1.2-1.4 mEq/L
0.9-1.1 mEq/L
0.6-0.8 mEq/L
Hyperglycemia
116-159 mg/dL
160-249 mg/dL
250-400 mg/dL
Hypoglycemia
55-65 mg/dL
40-54 mg/dL
30-39 mg/dL
Hematology
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Hemoglobin for children greater 
than 3 months and less than 2 
years of age
9.0-9.9 mg/dL
7.0-8.9 mg/dL
<7.0 mg/dL
Hemoglobin for children greater 
than 2 years of age
10.0-10.9 mg/dL
7.0-9.9 mg/dL
<7.0 mg/dL
Absolute neutrophil count
750-1200/mm3
400-749/mm3
250-399/mm3
Platelets
-
50,000-75,000/mm3
25,000-49,999/mm3
PT
1.1-1.2 x ULN
1.3-1.5 x ULN
1.6-3.0 x ULN
PTT
1.1-1.6 x ULN
1.7-2.3 x ULN
2.4-3.0 x ULN
Urinalysis
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Proteinuria
1+ or < 150 mg/day
2+ or 150-499 mg/day
3+ or 500-1000 mg/day
Hematuria
Microscopic <25 cells/hpf
Microscopic >25 cells/hpf
-

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
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Status: Approved, Date: 4 May 2017
Attachment 4:
Hemoglobin Cut-off Values
Where no institutional normal reference ranges is available for hemoglobin, the following cut-off values are 
proposed. It is imperative to note that there are no standard accepted normative values for hemoglobin in most 
African countries and therefore, the following recommendations are based on the review of several published 
sources and in consultation with the sites involved with the study. In the table below, ‘simplified’ means that the 
number of cut-off categories has been reduced to decrease complexity and facilitate understanding about eligibility. 
Similarly, ‘adjusted for safety’ means that the references may quote lower average or -2 SD values for hemoglobin 
but these values are considered to be too low for these subjects.  
Group
Value (g/dL)
Reference
Outcome
Adult and HIV+
Male 
12.1 
Female 
9.5
LLN value for local sites in Kenya and 
Uganda, current values being used in 
Phase 1
Values kept for consistency
Adolescent 16-18 yrs
Male 
12.1 
Female 
9.5 
Robins reference 10.4 g/dL for girls 
and 12.4 g/dL for boys
Values simplified to 
correspond to adult cut-offs
Adolescent 11-15 yrs
Male 
11.0 
Female 
9.5 
Robins reference 11.0 g/dL for girls 
and boys
Value adjusted down for 
boys, no change for girls
Children 6-10 yrs
11.0 
Robins reference 10.7 g/dL for girls 
and boys
Value simplified
Children 2-5 yrs
11.0 
Robins reference 10.4 g/dL for girls 
and boys, LLN value for local lab in 
Kenya 11.5 g/dL for girls and 
14.5 g/dL for boys, 
Schellenberg reference 8.2-9.3 g/dL 
average anemic defined as 
<11.0 g/dL 
Value simplified and 
adjusted for safety to 
11.0 g/dL
Children 1-2 yrs
11.0 
Schellenberg reference 8.0 g/dL 
average anemic defined as 
<11.0 g/dL, 
DMID toxicity table 11.0 g/dL
Value simplified and 
adjusted for safety to 
11.0 g/dL
Robins E and Blum S. Hematologic Reference Values for African American Children and Adolescents. American J 
Hematology. 2007:82, 611-614.
Schellenberg D, et al. The silent burden of anaemia in Tanzanian children: a community-based study. Bulletin of the 
World Health Organization 2003;81:581-590.
DMID US FDA Guidance document DIVISION OF MICROBIOLOGY AND INFECTIOUS DISEASES (DMID) 
PEDIATRIC TOXICITY TABLES NOVEMBER 2007

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2002 Amendment 3
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Status: Approved, Date: 4 May 2017
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
08May2017, 12:20:28 PM, UTC
Document Approval