A Randomized, Observer-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Safety, Tolerability and Immunogenicity of Three Prime-Boost Regimens of the Candidate Prophylactic Vaccines for Ebola Ad26.ZEBOV and MVA-BN-Filo in Healthy Adults in Europe
Phase: PHASE2
Conditions: Ebola Viral Disease
Sponsor: Janssen Vaccines & Prevention B.V.

1
Status: Approved, Date: 20 April 2017
Janssen Vaccines & Prevention B.V.*
Clinical Protocol
A Randomized, Observer-blind, Placebo-controlled, Phase 2 Study to Evaluate the Safety, 
Tolerability and Immunogenicity of Three Prime-boost Regimens of the Candidate Prophylactic 
Vaccines for Ebola Ad26.ZEBOV and MVA-BN-Filo in Healthy Adults in Europe
Protocol VAC52150EBL2001; Phase 2
AMENDMENT 5
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.
EudraCT NUMBER: 2015-000596-27
Status:
Approved  
Date:
20 April 2017
Prepared by:
Janssen Vaccines & Prevention B.V.  
EDMS number:
EDMS-ERI-98259076, 16.0
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.
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
2
Approved, Date: 20 April 2017
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF ATTACHMENTS............................................................................................................................ 4
LIST OF IN-TEXT TABLES.......................................................................................................................... 4
PROTOCOL AMENDMENTS....................................................................................................................... 5
SYNOPSIS.................................................................................................................................................. 18
TIME AND EVENTS SCHEDULE .............................................................................................................. 25
ADDITIONAL TIME AND EVENTS SCHEDULE .......................................................................................28
ABBREVIATIONS ...................................................................................................................................... 30
DEFINITIONS OF TERMS..........................................................................................................................31
1.
INTRODUCTION................................................................................................................................32
1.1.
Background.................................................................................................................................... 32
Nonclinical Studies ..................................................................................................................... 32
1.1.1.
Clinical Studies ...........................................................................................................................34
1.1.2.
1.1.2.1.
Safety Profile of Ad26-based Vaccines................................................................................... 34
1.1.2.2.
Safety Profile of MVA-BN-based Vaccines ............................................................................. 36
1.1.2.3.
Relevant Safety Information from Ongoing VAC52150 Studies.............................................. 37
1.1.2.4.
Viral Shedding .........................................................................................................................37
1.2.
Risk Benefit Section.......................................................................................................................38
Known Benefits...........................................................................................................................38
1.2.1.
Potential Benefits........................................................................................................................38
1.2.2.
Known Risks...............................................................................................................................38
1.2.3.
Potential Risks............................................................................................................................38
1.2.4.
Overall Benefit/Risk Assessment ...............................................................................................40
1.2.5.
1.3.
Overall Rationale for the Study...................................................................................................... 41
2.
OBJECTIVES AND HYPOTHESIS ................................................................................................... 43
2.1.
Objectives ...................................................................................................................................... 43
2.2.
Hypothesis ..................................................................................................................................... 43
3.
STUDY DESIGN AND RATIONALE ................................................................................................. 43
3.1.
Overview of Study Design.............................................................................................................. 43
3.2.
Study Design Rationale.................................................................................................................. 48
4.
SUBJECT POPULATION.................................................................................................................. 50
4.1.
Inclusion Criteria ............................................................................................................................51
4.2.
Exclusion Criteria ...........................................................................................................................52
4.3.
Prohibitions and Restrictions ......................................................................................................... 55
5.
TREATMENT ALLOCATION AND BLINDING................................................................................. 56
6.
DOSAGE AND ADMINISTRATION .................................................................................................. 58
6.1.
General Instructions and Procedures ............................................................................................58
6.2.
Criteria for Postponement of Vaccination ...................................................................................... 58
6.3.
Contraindications to Boost Vaccination .........................................................................................59
7.
TREATMENT COMPLIANCE............................................................................................................ 59
8.
PRESTUDY AND CONCOMITANT THERAPY ................................................................................ 60
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VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
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Approved, Date: 20 April 2017
9.
STUDY EVALUATIONS.................................................................................................................... 61
9.1.
Study Procedures...........................................................................................................................61
Overview..................................................................................................................................... 61
9.1.1.
Screening Phase ........................................................................................................................63
9.1.2.
Vaccination Phase......................................................................................................................64
9.1.3.
Post-vaccination Phase .............................................................................................................. 65
9.1.4.
Open-label Long-term Follow-up Phase..................................................................................... 66
9.1.5.
VAC52150 Vaccine Development Roll-over Study .................................................................... 67
9.1.6.
9.2.
Safety Evaluations .........................................................................................................................67
Safety Endpoints.........................................................................................................................67
9.2.1.
Safety Assessments ................................................................................................................... 67
9.2.2.
Pausing Rules.............................................................................................................................72
9.2.3.
9.3.
Immunogenicity Evaluations .......................................................................................................... 73
Immunogenicity Endpoints.......................................................................................................... 73
9.3.1.
Immunogenicity Assessments.................................................................................................... 74
9.3.2.
9.4.
Vaccine-induced Seropositivity...................................................................................................... 76
9.5.
Sample Collection and Handling.................................................................................................... 77
10.
SUBJECT COMPLETION/DISCONTINUATION OF STUDY 
VACCINATION/WITHDRAWAL FROM THE STUDY....................................................................... 77
10.1.
Completion..................................................................................................................................... 77
10.2.
Discontinuation of Study Vaccination/Withdrawal From the Study................................................ 77
10.3.
Withdrawal From the Use of Research Samples........................................................................... 79
11.
STATISTICAL METHODS................................................................................................................. 79
11.1.
Analysis Sets.................................................................................................................................. 80
11.2.
Sample Size Determination ........................................................................................................... 80
11.3.
Subject Information ........................................................................................................................81
11.4.
Safety Analyses .............................................................................................................................81
11.5.
Immunogenicity Analyses .............................................................................................................. 82
11.6.
Interim Analyses.............................................................................................................................82
11.7.
Independent Data Monitoring Committee ...................................................................................... 83
11.8.
Trial Management Team and Clinical Steering Committee ...........................................................83
12.
ADVERSE EVENT REPORTING ...................................................................................................... 83
12.1.
Definitions ...................................................................................................................................... 83
Adverse Event Definitions and Classifications ........................................................................... 83
12.1.1.
Attribution Definitions.................................................................................................................. 85
12.1.2.
Severity Criteria ..........................................................................................................................86
12.1.3.
12.2.
Special Reporting Situations.......................................................................................................... 87
12.3.
Procedures..................................................................................................................................... 87
All Adverse Events......................................................................................................................87
12.3.1.
Serious Adverse Events ............................................................................................................. 88
12.3.2.
Immediate Reportable Events .................................................................................................... 89
12.3.3.
Pregnancy................................................................................................................................... 89
12.3.4.
12.4.
Contacting Sponsor Regarding Safety...........................................................................................90
13.
PRODUCT QUALITY COMPLAINT HANDLING.............................................................................. 90
13.1.
Procedures..................................................................................................................................... 90
13.2.
Contacting Sponsor Regarding Product Quality............................................................................ 90
14.
STUDY VACCINE INFORMATION ................................................................................................... 91
14.1.
Description of Study Vaccines ....................................................................................................... 91
14.2.
Packaging and Labeling................................................................................................................. 91
14.3.
Preparation, Handling, and Storage...............................................................................................91
14.4.
Study Vaccine Accountability......................................................................................................... 92
15.
STUDY-SPECIFIC MATERIALS....................................................................................................... 93
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VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
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Approved, Date: 20 April 2017
16.
ETHICAL ASPECTS .........................................................................................................................93
16.1.
Study-specific Design Considerations ...........................................................................................93
16.2.
Regulatory Ethics Compliance....................................................................................................... 93
Investigator Responsibilities....................................................................................................... 93
16.2.1.
Independent Ethics Committee or Institutional Review Board ................................................... 94
16.2.2.
Informed Consent .......................................................................................................................95
16.2.3.
Privacy of Personal Data ............................................................................................................ 96
16.2.4.
Long-term Retention of Samples for Additional Future Research.............................................. 97
16.2.5.
Country Selection .......................................................................................................................97
16.2.6.
17.
ADMINISTRATIVE REQUIREMENTS ..............................................................................................97
17.1.
Protocol Amendments.................................................................................................................... 97
17.2.
Regulatory Documentation ............................................................................................................ 98
Regulatory Approval/Notification ................................................................................................98
17.2.1.
Required Prestudy Documentation.............................................................................................98
17.2.2.
17.3.
Subject Identification, Enrollment, and Screening Logs ................................................................99
17.4.
Source Documentation................................................................................................................... 99
17.5.
Case Report Form Completion .................................................................................................... 100
17.6.
Data Quality Assurance/Quality Control ...................................................................................... 100
17.7.
Record Retention .........................................................................................................................100
17.8.
Monitoring .................................................................................................................................... 101
17.9.
Study Completion/Termination..................................................................................................... 102
Study Completion/End of Study................................................................................................102
17.9.1.
Study Termination..................................................................................................................... 102
17.9.2.
17.10.
On-site Audits...............................................................................................................................102
17.11.
Use of Information and Publication..............................................................................................102
REFERENCES.......................................................................................................................................... 105
ATTACHMENTS....................................................................................................................................... 107
INVESTIGATOR AGREEMENT ............................................................................................................... 113
LAST PAGE.............................................................................................................................................. 113
LIST OF ATTACHMENTS
Attachment 1: 
Toxicity Tables for Use in Trials Enrolling Healthy Adults........................................... 107
LIST OF IN-TEXT TABLES 
Table 1:
Schematic Overview of Study Design, Cohorts and Groups.................................................... 44
Table 2:
Schematic Overview of Study Vaccination Schedules in the Three Groups Pooled 
Across Cohorts I, II and III ........................................................................................................ 45
Table 3:
Visit Windows............................................................................................................................62
Table 4:
Overview of Core Immunogenicity Assessments in Cohorts II and III...................................... 74
Table 5:
Overview of Specific Immunogenicity Assessments by Academic Consortium Partners 
in Cohort I ................................................................................................................................. 75
Table 6:
Overview of Additional Immunogenicity Assessments by Academic Consortium 
Partners in Cohort II.................................................................................................................. 76
Table 7:
Probability of Observing at Least One Adverse Event Given a True Adverse Event 
Incidence................................................................................................................................... 81
Table 8:
Magnitude of Pairwise Difference to be Detected Between Vaccine Regimens With 
Sample Size of 164 Subjects.................................................................................................... 81
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
5
Approved, Date: 20 April 2017
PROTOCOL AMENDMENTS
Protocol Version 
Issue Date
Amendment Type
Original Protocol
27 March 2015
-
Amendment 1
07 May 2015
Substantial
Amendment 2
18 August 2015
Substantial
Amendment 3
26 January 2016
Substantial
Amendment 4
01 September 2016
Substantial
Amendment 5
20 April 2017
Substantial
Amendments below are listed beginning with the most recent amendment.
Amendment_5 (this document)
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 was created due to significant delays in scheduled 
boost vaccinations caused by study pauses required for safety evaluations. Since many subjects in France have 
had no boost vaccination and many subjects in the United Kingdom (UK) have had a late boost vaccination, it 
will be very difficult to evaluate the planned dosing regimens. Therefore, no further subjects will be recruited in 
the entire study (ie, UK and France). Additional data on the planned dosing regimens will be obtained from other
studies. Vaccinated subjects in both countries will still be followed per protocol for safety.
The changes made to the clinical protocol VAC52150EBL2001 are listed below, including the rationale of each 
change and a list of all applicable sections.
Rationale: Due to significant delays in scheduled boost vaccinations caused by study pauses required for safety 
evaluations, enrollment in the entire study (ie, UK and France) will not be resumed. Since many subjects in 
France have had no boost vaccinations and many subjects in the UK have had a late boost vaccination, it will be 
very difficult to evaluate the planned dosing regimens. Therefore, no further subjects will be recruited in the
entire study (ie, UK and France).
SYNOPSIS
3 STUDY DESIGN AND RATIONALE
5 TREATMENT ALLOCATION AND BLINDING
9.1.2 Screening Phase
10.2 Discontinuation of Study Vaccination/Withdrawal From the Study
11.2 Sample Size Determination
Rationale: Subjects in France who agree to continue the long-term follow-up after Day 365 and reach the 
Day 365 visit before the roll-over study VAC52150EBL4001 is opened, will have further follow-ups in the 
current study until they have started in the roll-over study or for an additional 12 months (whichever comes first) 
or discontinued earlier. Information was added to clarify the procedures that need to be followed for these 
subjects.
SYNOPSIS
Time and Events Schedule
3.1 Overview of Study Design
9.1.1 Overview
9.1.5 Open-label Long-term Follow-up Phase
9.2.2 Safety Assessments
10.1 Completion
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VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
6
Approved, Date: 20 April 2017
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.
SYNOPSIS
2.1 Objectives
9.3.1 Immunogenicity Endpoints
Rationale: PBMC and serum samples for exploratory immunogenicity assessments collected in France may be 
analyzed in the UK and vice versa. Samples will be shared between clinical sites to allow exploratory 
immunogenicity endpoint analyses with the reduced subject numbers.
9.3.2 Immunogenicity Assessments
Rationale: As a result of the pause, the gap between the completion dates of the 2 countries (UK and France) will 
be smaller than originally expected. Therefore, it is no longer necessary to unblind by country. 
SYNOPSIS
Time and Events Schedule
Additional Time and Events Schedule
3.1 Overview of Study Design
5 TREATMENT ALLOCATION AND BLINDING
9.1.5 Open-label Long-term Follow-up Phase
Rationale: A statement has been added that due to delays in scheduled boost vaccinations caused by study 
pauses, the primary and final statistical analysis may be combined. 
11 STATISTICAL METHODS
Rationale: The statement that pre-specified decision criteria will be used for vaccination schedule selection, 
based on immune response results and absence of safety concerns, was removed. The majority of the studies were
designed in parallel because of the outbreak of the Ebola virus disease and decisions were made based on 
available data instead.
3.2 Study Design Rationale
Rationale: The statistical methods for clinical laboratory tests, vital signs, ECGs, and physical examination were 
revised. Since only small mean fluctuations are expected, limited interest will be on the summary statistics over 
time and the analyses will focus on worst abnormalities and toxicity gradings.
SYNOPSIS
11.4 Safety Analyses
Rationale: Information was added regarding the immunogenicity analysis.
11.1 Analysis Sets
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VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
7
Approved, Date: 20 April 2017
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
ABBREVIATIONS
3 STUDY DESIGN AND RATIONALE
4 SUBJECT POPULATION
5 TREATMENT ALLOCATION AND BLINDING
8 PRESTUDY AND CONCOMITANT THERAPY
9.1.1 Overview
9.1.2 Screening Phase
9.1.6 VAC52150 Vaccine Development Roll-over Study
9.2.2 Safety Assessments
9.3.2 Immunogenicity Assessments
10.1 Completion
11 STATISTICAL METHODS
Rationale: The protocol has been updated to be in line with the current protocol template (version 
1 November 2016).
TITLE PAGE
12.1.1 Adverse Event Definitions and Classifications
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VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
8
Approved, Date: 20 April 2017
Amendment_4 (01 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: The sponsor halted vaccinations following a case of Miller Fisher 
syndrome after receipt of MVA-BN-Filo or placebo in this clinical study, until a revised ICF containing updated 
safety language for the current study VAC52150EBL2001 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. As requested by the Agence Nationale de Sécurité du Médicament et des produits de santé
(ANSM), wording on the collection of Immediate Reportable Events was added after observation of the case of 
Miller Fisher syndrome. Randomization to Group 3 will be stopped to focus on the schedules for which an 
indication will be sought.
The changes made to the clinical protocol VAC52150EBL2001 are listed below, including the rationale of each 
change and a list of all applicable sections.
Rationale: As requested by the ANSM, wording on the collection of “Immediate Reportable Events” was added 
after one subject in this study 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
Additional Time and Events Schedule
1.1.2.3 Relevant Safety Information from Ongoing VAC52150 Studies
1.2.5 Overall Benefit/Risk Assessment
3.1 Overview of Study Design
8 PRESTUDY AND CONCOMITANT THERAPY
9.1.3 Vaccination Phase
9.1.4 Post-vaccination Phase
9.1.5 Open-label Long-term Follow-up Phase
9.2.1 Safety Endpoints
9.2.2 Safety Assessments
12.1.1 Adverse Event Definitions and Classifications
12.2 Special Reporting Situations
12.3.1 All Adverse Events
12.3.3 Immediate Reportable Events
Rationale: As a result of the pause, some subjects will be outside the protocol-defined boost vaccination 
window. Information was added to clarify the procedures that need to be followed for these subjects.
SYNOPSIS
Time and Events Schedule
Additional Time and Events Schedule
3.1 Overview of Study Design
11.5 Immunogenicity Analyses
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VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
9
Approved, Date: 20 April 2017
Rationale: As a result of the pause, subjects whose screening period was longer than the protocol-defined 
12 weeks will be allowed to rescreen once, but must have safety laboratory assessments (ie, serum chemistry and 
hematology, troponin I testing, serology, pregnancy testing, urinalysis) within 28 days of the prime vaccination.
Time and Events Schedule
3.1 Overview of Study Design
9.1.2 Screening Phase
Rationale: Randomization to Group 3 will be stopped to focus on the schedules for which an indication will be 
sought.
SYNOPSIS
3.1 Overview of Study Design
3.2 Study Design Rationale
5 TREATMENT ALLOCATION AND BLINDING
10.2 Discontinuation of Study Vaccination/Withdrawal From the Study
11.2 Sample Size Determination
Rationale: The percentage of subjects who will have blood samples taken for assessment of cellular immune 
responses was decreased from a target of 50% to 10% of all subjects.
SYNOPSIS
Time and Events Schedule
3.1 Overview of Study Design
9.3.2 Immunogenicity Assessments
Rationale: It was clarified that in France, blood samples will be collected from and analyzed in no more than
25 subjects in Groups 1 and 2. Collection and analysis of blood samples in France in Group 3 was deleted, 
because randomization to this group will be stopped.
Additional Time and Events Schedule
9.3.2 Immunogenicity Assessments
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
9.2.2 Safety Assessments
12.2 Special Reporting Situations
Rationale: Further details regarding enrollment into the VAC52150 roll-over study have been added, such as the 
inclusion of placebo subjects before unblinding of the current study.
SYNOPSIS
3.1 Overview of Study Design
9.1.6 VAC52150 Vaccine Development Roll-over Study
12.3.4 Pregnancy
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
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Approved, Date: 20 April 2017
Rationale: All secondary immunogenicity objectives and endpoints were shifted to exploratory objectives and 
endpoints, except for immune responses measured by ELISA.
SYNOPSIS
2.1 Objectives
9.3.1 Immunogenicity Endpoints
Rationale: Safety information following MVA-BN-Filo vaccine administration based on the pooled safety data 
from studies VAC52150EBL1001 and VAC52150EBL1002 has been included.
1.1.2.2 Safety Profile of MVA-BN-based Vaccines
REFERENCES
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
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
ABBREVIATIONS
1.1.2 Clinical Studies
1.3 Overall Rationale for the Study
2.1 Objectives
3.1 Overview of Study Design
4.1 Inclusion Criteria
10.2 Discontinuation of Study Vaccination/Withdrawal From the Study
11 STATISTICAL METHODS
11.1 Analysis Sets
11.2 Sample Size Determination
12.1.1 Adverse Event Definitions and Classifications
Rationale: The protocol has been updated to be in line with the current protocol template (version 6 June 2016).
4.1 Inclusion Criteria
17.5 Case Report Form Completion
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VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
11
Approved, Date: 20 April 2017
Amendment_3 (26 January 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 US Food and Drug Administration [FDA]) to extend the safety 
follow-up to 6 months post-boost. This request was originally made for protocols VAC52150EBL3002 and 
VAC52150EBL3003 and has now also been implemented for this protocol.
The changes made to the clinical protocol VAC52150EBL2001 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 6-month visit has been changed to 6-month post-boost 
visit. In addition, a statement has been added that subjects who already attended the 6-month post-prime visit 
(which has been replaced with the 6-month post-boost visit per the current protocol amendment) will be required 
to also attend the 6-month post-boost visit.
SYNOPSIS
Time and Events Schedule
Additional Time and Events Schedule
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 Open-label Long-term Follow-up Phase
11.5 Immunogenicity Analyses
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.
Time and Events Schedule
4.1 Inclusion Criteria
9.1.2 Screening Phase
Rationale: The time of unblinding and database lock for primary analysis has been changed to when all subjects 
have completed the 6-month post-boost visit or discontinued earlier. Subjects who received placebo and reach the 
Day 365 visit prior to unblinding will be required to attend the Day 365 visit.
SYNOPSIS
Time and Events Schedule
Additional Time and Events Schedule
3.1 Overview of Study Design
5 TREATMENT ALLOCATION AND BLINDING
9.1.5 Open-label Long-term Follow-up Phase
10.1 Completion
11 STATISTICAL METHODS
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VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
12
Approved, Date: 20 April 2017
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 
Rationale: 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 Inclusion Criteria
4.3 Prohibitions and Restrictions
Rationale: A statement has been added to allow enrollment of site staff or their family members, provided this is 
governed by institutional procedures and that there is no direct involvement in the proposed study or relationship 
with the investigator.
4.2 Exclusion Criteria
Rationale: One case of chest pain that might be indicative of pericarditis observed in the MVA-BN clinical trial 
program has been added to the Potential Risks section.
1.2.4 Potential Risks
Rationale: The analysis to estimate survival based on immunobridging methodology, linking NHP immune 
response data with human immune response data, will be described in a separate SAP.
11 STATISTICAL METHODS
Rationale: The analysis of response patterns over time for the immunologic parameters was deleted, since this 
analysis will not be performed.
SYNOPSIS
11.5 Immunogenicity Analyses
Rationale: Information regarding the marketing authorization of MVA-BN and the Phase 3 clinical study 
POX-MVA-013 has been updated.
1.1 Background
REFERENCES
Rationale: The VAC52150 Vaccine Development Registry was replaced by a roll-over study. Further details 
regarding enrollment have been added.
SYNOPSIS
3.1 Overview of Study Design
9.1.6 VAC52150 Vaccine Development Roll-over Study
12.3.4 Pregnancy
Rationale: Immunogenicity objectives, endpoints and assessments have been revised and corrected.
SYNOPSIS
2.1 Objectives
9.3 Immunogenicity Evaluations
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
13
Approved, Date: 20 April 2017
Rationale: The protocol has been updated to be in line with the current protocol template (version 14 October 
2015).
4 SUBJECT POPULATION
9.1.3 Vaccination Phase
9.1.4 Post-vaccination Phase
9.2.2 Safety Assessments
9.5 Sample Collection and Handling
10 SUBJECT COMPLETION/DISCONTINUATION OF STUDY VACCINATION/WITHDRAWAL FROM 
THE STUDY
12.1.1 Adverse Event Definitions and Classifications
12.2 Special Reporting Situations
12.3.4 Pregnancy
12.4 Contacting Sponsor Regarding Safety
13.2 Contacting Sponsor Regarding Product Quality
16.2.2 Independent Ethics Committee or Institutional Review Board
16.2.3 Informed Consent
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
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
14
Approved, Date: 20 April 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
Definitions of Terms
1 INTRODUCTION
3 STUDY DESIGN AND RATIONALE
5 TREATMENT ALLOCATION AND BLINDING
6.2 Criteria for Postponement of Vaccination
6.3 Contraindications to Boost Vaccination
9.1.1 Overview
9.1.2 Screening Phase
9.1.3 Vaccination Phase
9.1.5 Open-label Long-term Follow-up Phase
9.2.2 Safety Assessments
9.2.3 Pausing Rules
11.2 Sample Size Determination
11.4 Safety Analyses
REFERENCES
ATTACHMENTS
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
15
Approved, Date: 20 April 2017
Amendment_2 (18 August 2015)
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 was created to implement site-specific requests and 
additional changes.
The table below gives an overview of the rationale for each change and all applicable sections. 
The following changes were made on site-specific request:
Rationale: In the amendment, a statement was added to clarify that subjects who received placebo and reach the 
Day 180 visit prior to unblinding will be required to attend the Day 180 visit. After unblinding, only subjects who 
received active vaccine will enter a long-term follow-up phase.
SYNOPSIS
Time and Events Schedule
Additional Time and Events Schedule
3.1 Overview of Study Design
5 TREATMENT ALLOCATION AND BLINDING
9.1.5 Open-label Long-term Follow-up Phase
Rationale: In the amendment, a statement was added to clarify that the 42-days post-boost (Cohorts I and II), 
Day 180 and Day 365 visits (Cohort I) may be replaced by a telephone call if the subject is not able to come to 
the site.
Time and Events Schedule
9.1.1 Overview
9.1.4 Post-vaccination Phase
9.1.5 Open-label Long-term Follow-up Phase
Rationale: In the amendment, the Day 180 visit window has been extended from 15 to 30 days. 
9.1.1 Overview
Rationale: Modifications for clarity throughout the document.
SYNOPSIS
6.1 General Instructions and Procedures
The following additional changes were made:
Rationale: In the amendment, a statement was added to clarify that unblinding and clinical database lock will be 
done by country.
SYNOPSIS
3.1 Overview of Study Design
5 TREATMENT ALLOCATION AND BLINDING
9.1.5 Open-label Long-term Follow-up Phase
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
16
Approved, Date: 20 April 2017
Rationale: Modifications for clarity throughout the document.
SYNOPSIS
Time and Events Schedule
Additional Time and Events Schedule
1.2.4 Potential Risks
1.2.5 Overall Benefit/Risk Assessment
3.1 Overview of Study Design
4.2 Exclusion Criteria
5 TREATMENT ALLOCATION AND BLINDING
9.2.2 Safety Assessments
11.1 Analysis Sets
11.5 Immunogenicity Analyses
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
17
Approved, Date: 20 April 2017
Amendment_1 (7 May 2015)
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 was created upon request of the Medicines and 
Healthcare Products Regulatory Agency (MHRA). Further modifications were made to implement a site-specific 
request, to update the list of references and to correct minor inconsistencies.
The table below gives an overview of the rationale for each change and all applicable sections. 
Rationale: In the amendment, ‘a severe (grade 3) (non-serious) adverse event considered to be at least possibly 
related to study vaccine (active vaccine or placebo) that persists for 3 or more days, or a severe (grade 3) (non-
serious) laboratory abnormality (including unexplained hematuria) considered to be at least possibly related to 
study vaccine (active vaccine or placebo)’ has been added as contraindication to boost vaccination as requested by 
the MHRA.
6.3 Contraindications to Boost Vaccination
Rationale: In the amendment, a statement has been added as requested by the MHRA to clarify that if any pausing 
rule is met, and following the IDMC review it is deemed appropriate to restart dosing, a request to restart dosing 
with pertinent data must be submitted to the health authorities as a request for a substantial amendment. Dosing can 
restart only after approval of a substantial amendment by the competent authority.
9.2.3 Pausing Rules
Rationale: In the original protocol it was stated that ‘a subject's study vaccine should be permanently discontinued
if (followed by a list of criteria)’. In the amendment, it is clarified as requested by the MHRA that ‘a subject's study 
vaccine will be permanently discontinued in case any of the following listed criteria is met’.
10.2 Discontinuation of Study 
Rationale: Wording was modified in the amendment following a site-specific request to allow study vaccine 
administration by unblinded study-site personnel. The definition has been modified accordingly and wording has 
been added to indicate that the study vaccine administrator will have no other study function.
Definitions of Terms
3.2 Study Design Rationale
5 TREATMENT ALLOCATION AND BLINDING
6.1 General Instructions and Procedures
7 TREATMENT COMPLIANCE
9.1.3 Vaccination Phase
14.3 Preparation, Handling, and Storage
Rationale: The reference list was updated to include the addendum to the Ad26.ZEBOV Investigator’s Brochure 
Edition 2 that was issued in April 2015.
1 INTRODUCTION
1.1 Background
REFERENCES
Rationale: Modifications to correct minor inconsistencies.
1.3 Overall Rationale for the Study
11.1 Analysis Sets
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
18
Approved, Date: 20 April 2017
SYNOPSIS
A Randomized, Observer-blind, Placebo-controlled, Phase 2 Study to Evaluate the Safety, Tolerability 
and Immunogenicity of Three Prime-boost Regimens of the Candidate Prophylactic Vaccines for Ebola 
Ad26.ZEBOV and MVA-BN-Filo in Healthy Adults in Europe
EudraCT number: 2015-000596-27
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. 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 3 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.
Secondary Objective
The secondary objective is to assess humoral immune responses, as measured by ELISA, to the EBOV 
GP 21 days post boost of 3 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.
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
19
Approved, Date: 20 April 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 3 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.

To assess the neutralizing capacity of the EBOV GP-specific humoral immune response, as 
measured by virus neutralization assay, at selected time points of 3 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.

To further explore humoral immune responses at selected time points to different EBOV GPs, 
filovirus GPs and/or TAFV NP as well as the adenovirus and/or MVA backbones of the various 
vaccination schedules tested, if assays are available. 

To explore cellular immune responses at selected time points to different EBOV GPs, filovirus GPs
and/or TAFV NP of the various vaccination schedules tested, if assays are available.
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 study is a randomized, observer-blind, placebo-controlled, parallel-group, multicenter, Phase 2 study 
to evaluate the safety, tolerability and immunogenicity of 3 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 
subjects in Europe (United Kingdom [UK] and France). The 3 prime-boost regimens will only differ 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 vaccination will be identical. 
The subject population will consist of healthy men and women aged between 18 and 65 years (inclusive), 
who never received a candidate Ebola vaccine before and have no prior exposure to Ebola virus 
(including travel to West Africa less than 1 month prior to screening) or a diagnosis of Ebola virus 
disease. 
At study entry, subjects were offered the option to enroll into Cohorts I, II, or III in the UK or into 
Cohorts II or III in France. In Cohorts II and III in both countries, core immunogenicity assessments 
(humoral and cellular assays) will be performed. In Cohort II in both countries, additional 
immunogenicity assessments will be done. In Cohort I, plasmablast response kinetics will be evaluated 
for the determination of the optimal sampling time points of the B-cell response as part of the additional 
immunogenicity assessments in Cohort II in the UK. In the UK, Cohorts I and III may start in parallel, 
while Cohort II in the UK can only start when the peak of B-cell response after prime vaccination in
Cohort I is identified. In France, Cohorts II and III may start in parallel (as there will be no Cohort I) and 
are independent of Cohort I in the UK. 
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
20
Approved, Date: 20 April 2017
Study 
Cohorts
Randomization Ratio 
(Active:Placebo)
Group 1
N=204
Group 2
N=204
Group 3*
N=204
Cohort Total
N=612
UK**
N=321
France**
N=291
Cohort I 
-
10/0
10/0
10/0
30
30
-
Cohort II 
14:1
84/6
84/6
84/6
270
135
135
Cohort III 
10:3
80/24
80/24
80/24
312
156
156
Groups 1, 2, and 3: prime on Day 1, followed by boost 28, 56 or 84 days after prime, respectively; N: number of 
subjects to receive study vaccine (Ad26.ZEBOV, MVA-BN-Filo or placebo)
* Randomization to Group 3 was stopped per Amendment 4 to focus on the schedules for which an indication will 
be sought.
** Enrollment in the entire study (ie, UK and France) will be stopped per Amendment 5.
Subjects in each cohort were randomized at baseline (on Day 1) in a 1:1:1 ratio to Groups 1, 2, and 3 
(ie, the vaccination schedule). Within each group in Cohort I, subjects will receive Ad26.ZEBOV and 
MVA-BN-Filo in an open-label fashion. Randomization in Cohorts II and III was stratified by country. 
Within each group in Cohorts II and III, subjects were randomized to receive the prime-boost vaccination 
with either Ad26.ZEBOV followed by MVA-BN-Filo, or placebo in a 14:1 and 10:3 ratio, respectively. 
Randomization in each group (for Cohorts II and III) was stratified further according to age at 
randomization (≤50 years, >50 years), with at least 20% (of the total of both cohorts) of subjects in the 
>50 years category. Note that enrollment will not be resumed.
Study-site personnel (except for those with primary responsibility for study vaccine preparation and 
dispensing), sponsor personnel and subjects in Cohorts II and III will be blinded to the study vaccine 
allocation until all subjects have completed the 6-month post-boost visit or discontinued earlier and the 
clinical database is locked. In case interim analyses will be performed, study-site personnel (except for 
those with primary responsibility for study vaccine preparation and dispensing), the sponsor (except for 
programming, statistics, clinical and clinical immunology personnel involved in the analysis, and the 
sponsor committee involved in making future decisions for the program) and subjects will remain blinded 
to study vaccine allocation until the primary analysis.
All subjects will receive the study vaccine through IM injection in the deltoid, either Ad26.ZEBOV 
(5x1010 vp) on Day 1, followed by a boost vaccination of MVA-BN-Filo (1x108 Inf.U, nominal titer) on 
Days 29, 57 or 85; or placebo (0.9% saline) on Day 1, followed by a boost vaccination of placebo 
(0.9% saline) on Days 29, 57 or 85.
The study consists of a screening phase of up to 12 weeks (starting from the moment the subject signs the 
informed consent form [ICF]), a vaccination phase in which subjects will be vaccinated at baseline 
(Day 1), followed by a boost vaccination on Days 29, 57 or 85, and a post-vaccination phase and long-
term follow-up phase until Day 365 (or until the start of the roll-over study or for an additional 12 months 
[whichever comes first] for subjects in France who agree to continue the long-term follow-up after 
Day 365, see details below). After unblinding, the subjects who received placebo in Cohorts II and III will 
be contacted by the site to communicate that they have completed the study and no further follow-up is 
required. Unblinding will be done when the last subject in the study completes the 6-month post-boost 
visit or discontinues earlier and the clinical database is locked. However, subjects who received placebo 
and reach the Day 365 visit prior to unblinding will be required to attend the Day 365 visit. After 
unblinding, only subjects who received Ad26.ZEBOV or MVA-BN-Filo will continue the study until the 
Day 365 (or until the start of the roll-over study or for an additional 12 months [whichever comes first]
for subjects in France who agree to continue the long-term follow-up after Day 365, see details below)
visit to assess long-term safety and immunogenicity.
An Independent Data Monitoring Committee (IDMC) will be commissioned for this study. 
The sponsor halted all vaccinations in this study due to the occurrence of a serious and very rare 
condition, Miller Fisher syndrome, reported in the current study VAC52150EBL2001, until a revised ICF 
containing updated safety language was prepared and approval to restart the study was granted by the 
relevant competent authority. The study pause interrupted dosing of subjects, some awaiting prime 
vaccination and some awaiting boost vaccination. When approval was granted in the UK to restart the 
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
21
Approved, Date: 20 April 2017
study under Amendment 4, the sponsor offered a late boost vaccination to those subjects who did not 
receive it yet, unless participants had withdrawn from the trial or were not eligible to receive the boost. 
Vaccinated subjects have been following the same post-boost vaccination schedule as those subjects 
unaffected by the pause. Subjects who did not receive the late boost were encouraged to return for the 
1-year post-prime visit. After restart of the study in the UK under Amendment 4, screening for Groups 1 
and 2 restarted, but randomization to Group 3 was stopped to focus on the schedules for which an 
indication will be sought. After approval of Amendment 5, enrollment in the entire study will be stopped.
Subjects in the UK and France who reach the Day 365 visit prior to unblinding will be approached to 
consent 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 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, 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. The parent(s)/legal guardian of children 
born to vaccinated female subjects who became pregnant with estimated conception within 28 days after 
vaccination with MVA-BN-Filo or within 3 months after vaccination with Ad26.ZEBOV, will also be 
approached to consent for enrollment of their offspring into the roll-over study, according to the same 
rules that apply for the other subjects. Subjects in France who agree to continue the long-term follow-up
after Day 365 and reach the Day 365 visit before the roll-over study is opened, will have further follow-
ups in the current study until they have started in the roll-over study or for an additional 12 months 
(whichever comes first) or discontinued earlier. These subjects will be contacted by telephone every 
3 months after Day 365 (subjects will only visit the site when clinically indicated) for the collection of 
information on adverse events, serious adverse events, and immediate reportable events (IREs) that were 
ongoing at the Day 365 visit, and to report and follow up on new serious adverse events, pregnancies, and
IREs.
SUBJECT POPULATION
Screening of subjects for eligibility was performed within 12 weeks before administration of the study 
vaccine on Day 1. The subject population will consist of healthy (on the basis of medical history, physical 
examination, electrocardiogram (ECG), vital signs, clinical laboratory testing, and clinical judgment) men 
and women aged between 18 and 65 years (inclusive), who have no prior exposure to Ebola virus 
(including travel to West Africa less than 1 month prior to screening) or a diagnosis of Ebola virus
disease. Subjects who received a candidate Ebola vaccine or any experimental candidate Ad26- or MVA-
based vaccine in the past or with known allergy or history of anaphylaxis or other serious adverse 
reactions to vaccines or vaccine products, including known allergy to egg, egg products and 
aminoglycosides will be excluded.
DOSAGE AND ADMINISTRATION
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.
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 1.9x108 Inf.U per dose (range 1.27 to 
2.67 x108 Inf.U), supplied in a single use vial (0.5 mL extractable);

Placebo: 0.9% saline, 0.5 mL extractable.
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
22
Approved, Date: 20 April 2017
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 
(eg, in case of grade 3 adverse events). 
Criteria for postponement of vaccination at the scheduled time for vaccine administration and 
contraindications to boost vaccination have been defined and will be applied by the investigator.
SAFETY EVALUATIONS
All safety evaluations will be performed as specified in the Time and Events Schedule. Safety will be 
evaluated in all subjects from the 3 cohorts.
Safety will be assessed by collection of solicited local and systemic adverse events (reactogenicity), 
unsolicited adverse events, IREs, and serious adverse events. 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 
post-vaccination, 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 record symptoms of solicited 
local and systemic adverse events in the diary in the evening after each vaccination and then daily for the 
next 7 days. The investigator will document unsolicited adverse events from signing of the ICF onwards 
until 42 days post-boost, and serious adverse events and IREs from signing of the ICF onwards until the 
end of the study. The primary endpoints are adverse events, serious adverse events, IREs, and solicited 
local and systemic adverse events. Adverse events that are ongoing at 42 days post-boost vaccination will 
be followed until resolution or stabilization. For subjects in France who agree to continue the long-term 
follow-up after Day 365 and reach the Day 365 visit before the roll-over study is opened, the investigator 
will document adverse events, serious adverse events, and IREs that were ongoing at the Day 365 visit, 
and new serious adverse events, pregnancies, and IREs from Day 365 onwards until the start of the roll-
over study or for an additional 12 months (whichever comes first) (or discontinued earlier).
Other safety assessments include clinical laboratory testing, ECGs, vital signs (blood pressure, pulse/heart 
rate, and body temperature), physical examination and pregnancy testing at the time points indicated in 
the Time and Events Schedule. 
The investigators, together with the sponsor’s medical monitor, will be responsible for the safety 
monitoring of the study, and will halt vaccination of further subjects in case any of the pre-specified 
pausing rules have been met. 
IMMUNOGENICITY EVALUATIONS
All immunogenicity evaluations will be performed as specified in the Time and Events Schedule and
Additional Time and Events Schedule.
Blood samples for core immunogenicity assessments (humoral and cellular assays) for the evaluation of 
secondary and exploratory endpoints as planned by the sponsor will be collected at the time points 
indicated in the Time and Events Schedule. Blood samples for assessment of humoral immune responses 
will be obtained from all subjects in Cohorts II and III. Blood samples for assessment of cellular immune 
responses will be obtained from subjects in Cohorts II and III at selected sites with the capabilities to 
process peripheral blood mononuclear cells (PBMC) (targeted at 10% of all subjects).
Blood samples for additional immunogenicity assessments for the evaluation of additional exploratory 
endpoints as planned by the academic consortium partners will be collected from subjects in Cohort II at 
the time points indicated in the Additional Time and Events Schedule. Blood samples for plasmablast 
response kinetics will be collected in Cohort I at the time points indicated in the Additional Time and 
Events Schedule for the determination of the optimal sampling time points of the B-cell response as part 
of the additional immunogenicity assessments in Cohort II in the UK.
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
23
Approved, Date: 20 April 2017
A blood sample for deoxyribonucleic acid (DNA) collection will be collected at baseline from subjects in 
Cohort II at selected sites (as part of the additional immunogenicity assessments by the academic 
consortium partners) and who consent separately to this component of the study. Subject participation in 
genomic research is optional. The goal of this genomic research is to allow the identification of genetic 
factors that may influence the immunogenicity, safety, or tolerability of Ad26.ZEBOV and 
MVA-BN-Filo. Since the sample size is small, analysis will focus on validation of genes identified as 
possibly associated with these factors in previous (non-Ebola) studies and control of gene expression.
Optional blood samples for transcriptomics will be collected from subjects in Cohorts I and II (as part of 
the specific and additional immunogenicity assessments by the academic consortium partners, 
respectively) and who consent separately to the transcriptomics component of the study. Blood samples 
will be collected at the specified time points (see Additional Time and Events Schedule). The goal is to 
assess the ribonucleic acid (RNA) transcriptome (gene expression) in a systems vaccinology approach to 
identify differentially expressed genes which relate to the immunologic and safety phenotype of the 
response to Ad26.ZEBOV and MVA-BN-Filo, and for analysis of antibody genes.
If subjects provide separate consent, leftover blood samples will be stored for possible future 
scientific/genetic research. Subjects can withdraw consent for their samples to be used for future research 
at any time.
STATISTICAL METHODS
An originally planned sample size of 612 subjects (pooled across the 3 cohorts) includes 492 subjects 
randomized to receive Ad26.ZEBOV and MVA-BN-Filo (in Cohorts II and III) to substantially contribute 
to an overall safety database of the Ad26.ZEBOV and MVA-BN-Filo prime-boost regimen. In Cohort I, 
30 subjects will receive Ad26.ZEBOV and MVA-BN-Filo in an open-label fashion. Recruitment in 
Group 3 was stopped per Amendment 4 to focus on the schedules for which an indication will be sought.
Enrollment in the entire study will be stopped per Amendment 5. Details on the impact on the power will 
be described in the Statistical Analysis Plan (SAP) and/or Clinical Study Report. 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 3.3%, 2.2% and 0.8% for sample sizes of 121, 174 and 499 subjects (ie, 
total number of subjects in Cohorts I, II, and III to receive Ad26.ZEBOV and/or MVA-BN-Filo), 
respectively.
Interim analyses may be performed during the study for regulatory purposes or for the purpose of 
informing future vaccine-related decisions in a timely manner. The primary analysis will be performed 
when all subjects have completed the 6-month post-boost visit or discontinued earlier and the clinical 
database is locked. This analysis will include 6-month post-boost safety and all available immunogenicity 
data up to this point. The final analysis will be performed when all subjects have completed the last study-
related visit or discontinued earlier. Specific details will be provided in the 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), by cohort and overall. 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, ECG parameters, and physical examination
following vaccination will be tabulated by most severe abnormality grade.
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
24
Approved, Date: 20 April 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 evaluated at the 21-day
post-boost, 6-month post-boost and Day 365 visits. 
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
25
Approved, Date: 20 April 2017
TIME AND EVENTS SCHEDULE
Cohorts I, II and III
Screening 
Phasea
(≤12 weeks)
Vaccination and Post-vaccination Phaseb,c
Long-term Follow-up 
Phasec,d
Group 1
Day 1
Day 4
Day 8
-
Day 29
Day 32
Day 36
Day 50 
Day 71b
Day 209
Day 365e
Group 2
-
Day 57
Day 60
Day 64
Day 78 
Day 99b
Day 237
Group 3
Day 15f
Day 85
Day 88
Day 92
Day 106
Day 127b
Day 265
Study Procedures
Prime
+3d pp
+7d pp
+14d pp
Boost
+3d pb
+7d pb
+21d pb
+42d pb
+6m pbg
+1y pp
Screening/Administrative 
Informed consenth
X
Inclusion/exclusion criteria
Xi
Medical history and demographics 
X
Prestudy therapiesj
X
Serum pregnancy testk
X
Serology (HIV-1/2, hepatitis B/C)
X
Follicle-stimulating hormone (FSH)l
X
Check clinical status + available data
  Xm
Randomization
X
Study vaccine administrationn
▲
▼
Safety Assessments
Urine pregnancy testk
Xo
Xo
Physical examinationp
Xp
Xo
X
X
Xf
Xo
X
X
X
X
X
X
Electrocardiogramq (ECG)
X
Xo
X
Vital signsr
X
Xo
Xo
Distribution of subject diarys
X
X
Review of subject diary by site staff
X
X
X
X
Adverse eventst
Continuous
Serious adverse events and immediate 
reportable eventsu
Continuous
Concomitant medications
X
X
X
X
Xf
X
X
X
X
X
Xv
Xv
Clinical Laboratory Assessments
Hematology, chemistry 
X
Xo
X
Xo
X
Troponin I
X
Urinalysis
X 
Core Immunogenicity Assessments 
(Cohorts II and III)w
Blood sampling for humoral assays 
Xo
Xf
   Xo,x
Xx
Xx
Xx
Xx
Blood sampling for cellular assays 
Xo
Xf
   Xo,x
Xx
Xx
Xx
Xx
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
26
Approved, Date: 20 April 2017
Additional (Cohort II) & Specific 
(Cohort I) Immunogenicity Assessmentsy
See Additional Time and Events Schedule
d pp: days post-prime; d pb: days post-boost; m pb: months post-boost; y pp: year post-prime; 
▲ Ad26.ZEBOV 5x1010 vp or placebo ▼ MVA-BN-Filo 1x108 Inf.U (nominal titer) or placebo. 
NOTE: If a subject withdraws early from the study, early withdrawal assessments should be obtained per the assessments for the 21-day post-boost visit. 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.
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, also for subjects who are rescreened due to a pause. 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. Similarly, subjects who are rescreened due to a pause must have new safety 
laboratory assessments within 28 days of the prime vaccination.
b
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. After unblinding, subjects who 
received placebo will be contacted by the site to communicate that they have completed the study and no further follow-up is required. Unblinding will be done 
when the last subject in the study completes the 6-month-post-boost visit or discontinues earlier and the clinical database is locked. However, subjects who received 
placebo and reach the Day 365 visit prior to unblinding will be required to attend the Day 365 visit. The 42-days post-boost visit may be replaced by a telephone call 
if the subject is not able to come to the site (only applies to Cohorts I and II).
c
For subjects who receive the boost vaccination outside the protocol-defined boost vaccination window due to pausing of the study, the timings of the next visits post 
boost vaccination will be determined relative to the actual day of boost vaccination. Subjects who did not receive the late boost vaccination were encouraged to 
return for the 1-year post-prime visit.
d
After unblinding, only subjects who received Ad26.ZEBOV or MVA-BN-Filo will be followed up for the collection of serious adverse event information, immediate 
reportable events and for blood draws for immunogenicity assessments after the 6-month post-boost visit. The 6-month post-boost and Day 365 visits may be 
replaced by a telephone call if the subject is not able to come to the site (only applies to Cohort I).
e
Subjects in France who agree to continue the long-term follow-up after Day 365 and who reach the Day 365 visit before the roll-over study VAC52150EBL4001 is 
opened, will have further follow-ups in the current study until they have started in the roll-over study or for an additional 12 months (whichever comes first) or
discontinued earlier. These subjects will be contacted by telephone every 3 months after Day 365 (subjects will only visit the site when clinically indicated) for the 
collection of information on adverse events, serious adverse events, and immediate reportable events that were ongoing at the Day 365 visit, and to report and follow 
up on new serious adverse events, pregnancies, and immediate reportable events. Concomitant therapies are only to be recorded if given in conjunction with serious 
adverse events and immediate reportable events.
f
Day 15 visit only for subjects in Group 3 of Cohort III.
g
Subjects who already attended the 6-month post-prime visit (which has been replaced with the 6-month post-boost visit per protocol amendment 3) will be required 
to also attend the 6-month post-boost visit.
h
Signing of the informed consent form (ICF) needs to be done before the first study-related activity.
i
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.
j
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).
k
For women of childbearing potential.
l
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.
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
27
Approved, Date: 20 April 2017
m
If a subject’s clinical status changes (including available laboratory results or receipt of additional medical records) after screening so the subject no longer meets 
eligibility criteria, the subject should be excluded from further participation in the study.
n
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.
o
Prior to study vaccine administration. 
p
A full physical examination, including height and body weight, will be carried out at screening. At other visits, an abbreviated, symptom-directed examination will 
be performed as indicated by the investigator. 
q
A single, 12-lead ECG (supine) after at least 5 minutes rest will be performed and interpreted locally. Additional ECG monitoring may be done at other time points 
during the study if clinically indicated based on signs and symptoms. If blood sampling or vital sign measurement is scheduled for the same time point as ECG 
recording, the procedures should be performed in the following order: vital signs, ECG(s), blood draw.
r
Includes blood pressure, pulse/heart rate (at rest) and body temperature to be assessed prior to study vaccine administration.
s
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.
t
Pregnancies will be reported from signing of the ICF until the end of the study.
u
For reporting of immediate reportable events, refer to Section 12.3.3.
v
Concomitant therapies must be recorded from screening onwards until 42 days after the boost vaccination. Thereafter, concomitant therapies are only to be recorded 
if given in conjunction with serious adverse events and immediate reportable events.
w
Only including the core immunogenicity assessments. Blood samples will be collected for humoral assays from all subjects in Cohorts II and III and for cellular 
assays from subjects in Cohorts II and III at selected sites with the capabilities to process PBMC (targeted at 10% of all subjects). 
x
Subjects who receive the boost vaccination outside the protocol-defined boost vaccination window due to pausing of the study, will only have blood samples taken to 
assess humoral immune responses measured at selected time points by ELISA. In addition, blood samples will be taken prior to the boost vaccination and at the
7-day post-boost visit for safety assessments.
y
For potential additional immunogenicity assessments in Cohort II and specific immunogenicity assessments in Cohort I, see Additional Time and Events Schedule.
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
28
Approved, Date: 20 April 2017
ADDITIONAL TIME AND EVENTS SCHEDULE 
Cohort I
Vaccination and Post-vaccination Phasea,b
Group 1
Day 1
Day 9
Day 11
Day 13
Day 15
Day 29
Day 32
Day 34
Day 36
Day 38
Group 2
Day 57
Day 60
Day 62
Day 64
Day 66
Group 3
Day 85
Day 88
Day 90
Day 92
Day 94
Prime
+8d pp
+10d pp
+12d pp
+14d pp
Boostl
+3d pbl
+5d pbl
+7d pbl
+9d pbl
Study vaccine administration
▲
▼
Specific Immunogenicity Assessments by 
University of Oxford – Blood sampling in UK for:
Determination of kinetics of B-cell response 
(B-cell ELISpot) 
Xc
X 
X 
X 
X
Xc
X
X
X
X
Transcriptomicsd
Xc
X 
X 
X 
X 
Xc
X 
X 
X
X
Cohort IIe
Vaccination and Post-vaccination Phasea,b
LT FU 
Phaseb,f
Group 1
Day 1
Day 2
Day 8
Day 15
TBDg
Day 29
Day 30
Day 36
Day 43
TBDg
Day 50
Day 209
Group 2
Day 57
Day 58
Day 64
Day 71
Day 78
Day 237
Group 3
Day 85
Day 86
Day 92
Day 99
Day 106
Day 265
Prime
+1d pp
+7d pp +14d pp
tbd
Boostl
+1d pbl
+7d pbl
+14d pbl
tbdl
+21d pbl
+6m pbh,l
Study vaccine administration
▲
▼
Additional Immunogenicity Assessments by 
University of Oxford – Blood sampling in UK for:
Repertoire sequencing, isolation of monoclonal 
Ab, plasmablast phenotyping 
Xc
Xg
Xc
Xg
Memory B-cell characterization 
Xc
Xc
X
X
DNA isolationi
Xc
Fresh intracellular cytokine staining (ICS)
Xc
Xc
X
Transcriptomicsd
Xc
Xg
Xc
Xg
Additional Immunogenicity Assessments by 
INSERM – Blood sampling in France for:
Natural killer (NK) cell analysisj
Xc
Xc
X 
X 
Transcriptomicsd
Xk
X 
X
Xk
X
X 
Fresh ICS 
Xc
Xc
X
T cell proliferation 
Xc
X
Xc
X 
X 
T cell phenotyping (including TfH) 
Xc
X 
Xc
X 
Cytokine profiling 
Xc
X 
X 
Xc
X 
X 
EBOV neutralization 
Xc
Xc
X 
X 
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
29
Approved, Date: 20 April 2017
Ab: antibodies; d pp: days post-prime; d pb: days post-boost; LT FU: long-term follow-up; m pb: months post-boost; TBD: to be determined; TfH: T follicular helper; 
▲ Ad26.ZEBOV 5x1010 vp or placebo  ▼ MVA-BN-Filo 1x108 Inf.U (nominal titer) or placebo.  
NOTE: In Cohort I, plasmablast response kinetics will be evaluated for the determination of the optimal sampling time points of the B-cell response as part of the 
additional immunogenicity assessments in Cohort II in the UK.
a
After unblinding, subjects who received placebo will be contacted by the site to communicate that they have completed the study and no further follow-up is 
required. Unblinding will be done when the last subject in the study completes the 6-month-post-boost visit or discontinues earlier and the clinical database is 
locked. However, subjects who received placebo and reach the Day 365visit prior to unblinding will be required to attend the Day 365 visit. 
b
For subjects who receive the boost vaccination outside the protocol-defined boost vaccination window due to pausing of the study, the timings of the next visits post 
boost vaccination will be determined relative to the actual day of boost vaccination.
c
Prior to study vaccine administration.
d
Optional blood sample for transcriptomics only to be obtained from subjects who consent separately. 
e
Blood samples will be collected for DNA isolation (in the UK), transcriptomics (in both countries), and EBOV neutralization (in France) from all subjects in 
Cohort II. For the other assays, blood samples will be collected from all subjects in Cohort II in the UK, but initially only 25 subjects per group will be targeted for 
analysis, while in France, blood samples will be collected from and analyzed in no more than 25 subjects in Groups 1 and 2 in Cohort II at selected sites. In addition, 
these ‘other’ assays have to be performed within the same 25 subjects per group in the UK and in France.
f
After unblinding, only subjects who received Ad26.ZEBOV or MVA-BN-Filo will be followed up for the collection of serious adverse event information, immediate 
reportable events, and for blood draws for immunogenicity assessments after the 6-month post-boost visit.
g
At plasmablast peak time point determined in Cohort I (only applies to Cohort II in the UK).
h
Subjects who already attended the 6-month post-prime visit (which has been replaced with the 6-month post-boost visit per protocol amendment 3) will be required 
to also attend the 6-month post-boost visit.
i
Optional blood sample for DNA collection only to be obtained from subjects who consent separately. The DNA sample should be collected at the specified time 
point; however, if necessary it may be collected at a later time point without constituting a protocol deviation.
j
Blood sampling done in France, but analysis performed at London School of Hygiene and Tropical Medicine.
k
Prior to study vaccine administration and at 3-4 hours after study vaccine administration.
l
Subjects who receive the boost vaccination outside the protocol-defined boost vaccination window due to pausing of the study, will not have specific or additional 
immunogenicity assessments at these visits.
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
30
Approved, Date: 20 April 2017
ABBREVIATIONS
Ad26
adenovirus serotype 26 (vector)
Ad26.ZEBOV
adenovirus serotype 26 expressing the Ebola virus Mayinga glycoprotein
Ad35
adenovirus serotype 35 (vector)
ALT
alanine aminotransferase
AST
aspartate aminotransferase
β-hCG
β-human chorionic gonadotropin
BN
Bavarian Nordic
BUN
blood urea nitrogen
CRF
case report form 
DNA
deoxyribonucleic acid
EBOV
Ebola virus
ECG
electrocardiogram
eDC
electronic data capture
EDTA
ethylenediaminetetraacetic acid
ELISA
enzyme-linked immunosorbent assay
ELISpot
enzyme-linked immunospot assay
EU
European Union
FSH
follicle stimulating hormone
GCP
Good Clinical Practice
GMP
Good Manufacturing Practice
GP
glycoprotein
HBsAg
hepatitis B surface antigen
HCV
hepatitis C virus
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
interferon
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
IUD
intrauterine device
IUS
intrauterine system
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 primates
NK
natural killer (cell)
NP
nucleoprotein
NSAID
nonsteroidal anti-inflammatory drug
PBMC
peripheral blood mononuclear cell(s)
PQC
product quality complaint
QTcB
QT interval corrected according to the Bazett formula
QTcF
QT interval corrected according to the Fridericia formula
RBC
red blood cell
RNA
ribonucleic acid
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
31
Approved, Date: 20 April 2017
SAP
Statistical Analysis Plan
SUDV
Sudan virus
SUSAR
suspected unexpected serious adverse reaction
TAFV
Tai Forest virus
TCID50
50% tissue culture infective dose
TfH
T follicular helper
THAM
tris (hydroxymethyl)-amino methane
TNF
tumor necrosis factor
TOPS
The Over-volunteering Prevention System
UK
United Kingdom
US
United States
VISP
vaccine-induced seropositivity
vp
viral particles
WBC
white blood cell
WHO
World Health Organization
DEFINITIONS OF TERMS
Study vaccine 
administrator
A trained study nurse, medical doctor, or otherwise qualified health care provider who 
will have no other study function.
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 9.2.2. 
For the purpose of vaccine clinical studies, all other adverse events are considered 
unsolicited; however, this definition should be distinguished from definitions based on 
pharmacovigilance guidelines.
Study vaccine
MVA-BN-Filo, Ad26.ZEBOV or placebo
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
32
Approved, Date: 20 April 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).12,13,14 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).26 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.9
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 
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
33
Approved, Date: 20 April 2017
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.
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
34
Approved, Date: 20 April 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.12,13,14
Limited data from the ongoing Phase 1 studies with Ad26.ZEBOV and MVA-BN-Filo are 
available. Study VAC52150EBL1001 completed enrollment of 87 subjects and the blinded phase 
of the study is ongoing. Study VAC52150EBL1002 completed enrollment of 92 subjects and the 
blinded phase of the study is also ongoing.
Safety data generated with the 2 vectors containing different inserts are provided below:
Safety Data From Other Ad26-based Vaccine Programs
Ad26.ZEBOV is a monovalent recombinant, 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.15
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.15,16,17

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
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
35
Approved, Date: 20 April 2017

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-month and 
6-month 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.01.19
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 
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
36
Approved, Date: 20 April 2017
the low and high-dose groups than by placebo subjects. There were no clinically significant 
changes in laboratory test parameters or vital signs data.5
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.22
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.
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.11 A Phase 3 clinical study
(POX-MVA-013) has been completed (ClinicalTrials.gov Identifier: NCT01144637).6 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.20 Across all clinical studies, no trends for 
unexpected or serious adverse reactions due to the product were detected. 
Safety 
information 
was 
combined 
from 
the 
first 
2 
studies 
of 
MVA-BN-Filo 
(VAC52150EBL1001 and VAC52150EBL1002). In general, MVA-BN-Filo has been shown to 
be well tolerated.14
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-
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
37
Approved, Date: 20 April 2017
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. 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.23,24
1.1.2.3.
Relevant Safety Information from Ongoing VAC52150 Studies
One subject in this study 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.12
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
38
Approved, Date: 20 April 2017
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.
1.2.
Risk Benefit 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.
There is no known potential individual benefit from vaccination for the subjects at the current 
stage; others may benefit from knowledge gained in this study that may aid in the development 
of an Ebola vaccine.
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 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 9.3.2.
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
39
Approved, Date: 20 April 2017
Risk of Myo/Pericarditis
While replicating smallpox vaccines have been associated with an increased risk to develop 
myo/pericarditis,21 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 
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 (0.3%) subject met 
the criteria for vaccine-induced myocarditis and eventually the subject was found to suffer from 
exercise-induced palpitations. Self-limited mild elevations in troponin I were recorded in 
3 (0.8%) subjects without evidence of myo/pericarditis.7 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 women of childbearing potential, and men having sexual intercourse with women, are 
required to agree to practice adequate birth control measures for sexual intercourse from at least 
28 days before the prime vaccination (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 
Sections 4.1 and 4.3. Women who are pregnant or breast-feeding, or are planning to become 
pregnant 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) will be excluded from enrollment 
into the study.
Women of childbearing potential must also agree not to donate eggs (ova, oocytes) for the 
purposes of assisted reproduction from the start of screening onwards until at least 3 months after 
the prime vaccination or up to 1 month after the boost vaccination (whichever takes longer). Men 
must also agree not to donate sperm from the start of screening onwards until at least 3 months 
after the prime vaccination or up to 1 month after the boost vaccination (whichever takes longer).
After unblinding for the primary analysis, placebo subjects may stop birth control measures or 
resume their pre-study birth control measures, and may donate eggs (women) or sperm (men).
Risks from Blood Draws
Blood draws may cause pain/tenderness, bruising, bleeding, and, rarely, infection at the site 
where the blood is taken.
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
40
Approved, Date: 20 April 2017
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.
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 Section 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:
After each vaccination, subjects will remain at the site for a total of 60 (±15) minutes 
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). 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 post-vaccination, and any unsolicited, solicited 
local or systemic adverse events will be documented during this period. Subjects will use a 
diary to document symptoms of solicited local and systemic adverse events in the evening 
after each vaccination and then daily for the next 7 days. 
The investigator or the designee will document unsolicited adverse events from signing of 
the informed consent form (ICF) onwards until 42 days post-boost, and serious adverse 
events and immediate reportable events (IREs) from signing of the ICF onwards until the 
end of the study.
Safety measures, including clinical laboratory testing, electrocardiogram (ECG) and vital 
sign measurements, physical examinations 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. 
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
41
Approved, Date: 20 April 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 9.2.3
for further details). 
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 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.
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.20 Although routinely used by the subcutaneous route, MVA-BN at a 
dose of 1x108 TCID50 (50% Tissue Culture Infective Dose) has been demonstrated to be as safe 
and immunogenic when used by the IM route.8,25 The IM route has been chosen for the present 
study. 
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
42
Approved, Date: 20 April 2017
The unprecedented size and scale of the ongoing Ebola virus 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 virus disease. 
It will test schedules 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. 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 priming immunization followed by MVA vector boost 
induced high levels of immunity.
For the prevention of Ebola virus disease, shorter 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 only differ 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.
This study aims to evaluate the safety, tolerability and immunogenicity of the 3 prime-boost 
regimens, only different in terms of vaccination schedule with a time interval of 28, 56 or 
84 days between the prime and the boost vaccination, and to enlarge the safety and 
immunogenicity database for the selected Ad26.ZEBOV and MVA-BN-Filo prime-boost 
regimen(s).
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
43
Approved, Date: 20 April 2017
2.
OBJECTIVES AND HYPOTHESIS
2.1.
Objectives
Primary Objective
The primary objective is to assess the safety and tolerability of 3 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.
Secondary Objective
The secondary objective is to assess humoral immune responses, as measured by ELISA, to the 
EBOV GP 21 days post boost of 3 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.
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 3 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.

To assess the neutralizing capacity of the EBOV GP-specific humoral immune response, as 
measured by virus neutralization assay, at selected time points of 3 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.

To further explore humoral immune responses at selected time points to different EBOV 
GPs, filovirus GPs and/or TAFV NP as well as the adenovirus and/or MVA backbones of 
the various vaccination schedules tested, if assays are available. 

To explore cellular immune responses at selected time points to different EBOV GPs,
filovirus GPs and/or TAFV NP of the various vaccination schedules tested, if assays are 
available.
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 to evaluate the safety, tolerability and immunogenicity of 3 heterologous prime-boost 
regimens using Ad26.ZEBOV at a dose of 5x1010 vp as prime and MVA-BN-Filo at a dose of 
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
44
Approved, Date: 20 April 2017
1x108 Inf.U (nominal titer) as boost at a 28-, 56- or 84-day interval in healthy adult subjects in 
Europe (United Kingdom [UK] and France). The 3 prime-boost regimens will only differ 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 vaccination will be identical. 
The subject population will consist of healthy men and women aged between 18 and 65 years 
(inclusive), who have no prior exposure to Ebola virus (including travel to West Africa less than 
1 month prior to screening) or a diagnosis of Ebola virus disease. Subjects who received a 
candidate Ebola vaccine or any experimental candidate Ad26- or MVA-based vaccine in the past 
or with known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or 
vaccine products, including known allergy to egg, egg products and aminoglycosides will be 
excluded.
At study entry, subjects were offered the option to enroll into Cohorts I, II, or III in the UK or 
into Cohorts II or III in France. In Cohorts II and III in both countries, core immunogenicity 
assessments (humoral and cellular assays) will be performed. In Cohort II in both countries,
additional immunogenicity assessments will be done. In Cohort I, plasmablast response kinetics 
will be evaluated for the determination of the optimal sampling time points of the B-cell 
response as part of the additional immunogenicity assessments in Cohort II in the UK. In the UK, 
Cohorts I and III may start in parallel, while Cohort II in the UK can only start when the peak of 
B-cell response after prime vaccination in Cohort I is identified. In France, Cohorts II and III 
may start in parallel (as there will be no Cohort I) and are independent of Cohort I in the UK. A 
schematic overview of the study design, cohorts and groups is provided in Table 1. 
Table 1:
Schematic Overview of Study Design, Cohorts and Groups
Study 
Cohorts
Randomization Ratio 
(Active:Placebo)
Group 1
N=204
Group 2
N=204
Group 3*
N=204
Cohort Total
N=612
UK**
N=321
France**
N=291
Cohort I 
-
10/0
10/0
10/0
30
30
-
Cohort II 
14:1
84/6
84/6
84/6
270
135
135
Cohort III 
10:3
80/24
80/24
80/24
312
156
156
Groups 1, 2 and 3: prime on Day 1, followed by boost 28, 56 or 84 days after prime, respectively; N: number of 
subjects to receive study vaccine (Ad26.ZEBOV, MVA-BN-Filo or placebo)
* Randomization to Group 3 was stopped per Amendment 4 to focus on the schedules for which an indication will 
be sought.
** Enrollment in the entire study (ie, UK and France) will be stopped per Amendment 5.
Subjects in each cohort were randomized at baseline (on Day 1) in a 1:1:1 ratio to Groups 1, 2 
and 3 (ie, the vaccination schedule). A schematic overview of the study vaccination schedules is 
provided in Table 2. Within each group in Cohort I, subjects will receive Ad26.ZEBOV and
MVA-BN-Filo in an open-label fashion. Randomization in Cohorts II and III was stratified by 
country. Within each group in Cohorts II and III, subjects were randomized to receive the prime-
boost vaccination with either Ad26.ZEBOV followed by MVA-BN-Filo, or placebo in a 14:1 
and 10:3 ratio, respectively (see Table 1). Randomization in each group (for Cohorts II and III) 
was stratified further according to age at randomization (≤50 years, >50 years), with at least 20% 
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
45
Approved, Date: 20 April 2017
(of the total of both cohorts) of subjects in the >50 years category. Note that enrollment will not 
be resumed.
Study-site personnel (except for those with primary responsibility for study vaccine preparation 
and dispensing), sponsor personnel and subjects in Cohorts II and III will be blinded to the study 
vaccine allocation until all subjects have completed the 6-month post-boost visit or discontinued 
earlier and the clinical database is locked. Refer to Section 5 for further details on blinding in 
case of interim analyses.
Table 2:
Schematic Overview of Study Vaccination Schedules in the Three Groups Pooled Across 
Cohorts I, II and III
Group*
N
Prime
Boost
Day 1
Day 29
Day 57
Day 85
1
204
174
Ad26.ZEBOV
MVA-BN-Filo
30
placebo 
placebo 
2
204
174
Ad26.ZEBOV
MVA-BN-Filo 
30
placebo 
placebo 
3**
204
174
Ad26.ZEBOV
MVA-BN-Filo 
30
placebo
placebo 
N: number of subjects to receive study vaccine (Ad26.ZEBOV, MVA-BN-Filo or placebo)
Ad26.ZEBOV dose level is 5x1010 vp in all groups, MVA-BN-Filo dose level is 1x108 Inf.U (nominal titer) in all 
groups, placebo is 0.9% saline
* Enrollment in the entire study (ie, UK and France) will be stopped per Amendment 5.
** Randomization to Group 3 was stopped per Amendment 4 to focus on the schedules for which an indication will 
be sought.
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, nominal titer) on Days 29, 57 or 85; OR
Placebo (0.9% saline) on Day 1, followed by a boost vaccination of placebo (0.9% saline) on 
Days 29, 57 or 85.
Refer to Section 6 for further details on dosage and administration. 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 (eg, in 
case of grade 3 adverse events).
The study consists of a screening phase of up to 12 weeks (starting from the moment the subject 
signs the ICF), a vaccination phase in which subjects will be vaccinated at baseline (Day 1), 
followed by a boost vaccination on Days 29, 57 or 85, and a post-vaccination phase and long-
term follow-up phase until Day 365 (or until the start of the roll-over study or for an additional 
12 months [whichever comes first] for subjects in France who agree to continue the long-term 
follow-up after Day 365, see details below and Section 9.1.5). After unblinding, the subjects who 
received placebo in Cohorts II and III will be contacted by the site to communicate that they 
have completed the study and no further follow-up is required. Unblinding will be done when the 
last subject in the study completes the 6-month post-boost visit or discontinues earlier and the 
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
46
Approved, Date: 20 April 2017
clinical database is locked. However, subjects who received placebo and reach the Day 365 visit 
prior to unblinding will be required to attend the Day 365 visit. After unblinding, only subjects 
who received Ad26.ZEBOV or MVA-BN-Filo will continue the study until Day 365 (or until the 
start of the roll-over study or for an additional 12 months [whichever comes first] for subjects in 
France who agree to continue the long-term follow-up after Day 365, see details below and 
Section 9.1.5) visit to assess long-term safety and immunogenicity. Refer to Section 9.1.2 for 
subjects whose screening period was longer than the protocol-defined 12 weeks as a result of a
pause.
The baseline visit may be scheduled as soon as the results of all screening assessments are 
known (but should occur within 12 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. 
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 9.2.3 have been met. In addition, discontinuation 
of study vaccine should occur in any subject meeting the criteria outlined in Section 10.2. 
Criteria for postponement of vaccination at the scheduled time for vaccine administration and 
contraindications to boost vaccination have been defined and will be applied by the investigator 
(see Sections 6.2 and 6.3, respectively).
Safety will be assessed in all subjects from the 3 cohorts by collection of solicited local and 
systemic adverse events (reactogenicity), unsolicited adverse events, IREs and serious adverse 
events. 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 post-vaccination, 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 record symptoms of solicited local 
and systemic adverse events in the diary in the evening after each vaccination and then daily for 
the next 7 days. The investigator will document unsolicited adverse events from signing of the 
ICF onwards until 42 days post-boost, and serious adverse events and IREs from signing of the 
ICF onwards until the end of the study. The primary endpoints are adverse events, serious 
adverse events, IREs, and solicited local and systemic adverse events, see Section 9.2.1. 
Other safety assessments include clinical laboratory testing, ECGs, vital signs (blood pressure,
pulse/heart rate, and body temperature), physical examination and pregnancy testing at the time 
points indicated in the Time and Events Schedule. 
Blood samples for core immunogenicity assessments (humoral and cellular assays) for the 
evaluation of secondary and exploratory endpoints as planned by the sponsor (see Table 4 in 
Section 9.3.2) will be collected at the time points indicated in the Time and Events Schedule. 
Blood samples for assessment of humoral immune responses will be obtained from all subjects in
Cohorts II and III. Blood samples for assessment of cellular immune responses will be obtained 
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
47
Approved, Date: 20 April 2017
from subjects in Cohorts II and III at selected sites with the capabilities to process peripheral 
blood mononuclear cells (PBMC) (targeted at 10% of all subjects).
Blood samples for additional immunogenicity assessments for the evaluation of additional 
exploratory endpoints as planned by the academic consortium partners will be collected from
subjects in Cohort II (see Table 6 in Section 9.3.2) at the time points indicated in the Additional
Time and Events Schedule. Blood samples for plasmablast response kinetics will be collected in 
Cohort I (see Table 5) at the time points indicated in the Additional Time and Events Schedule
for the determination of the optimal sampling time points of the B-cell response as part of the 
additional immunogenicity assessments in Cohort II in the UK.
A blood sample for DNA collection will be collected at baseline from subjects in Cohort II at 
selected sites (as part of the additional immunogenicity assessments by the academic consortium 
partners, see Table 6) and who consent separately to this component of the study. Subject 
participation in genomic research is optional. The goal of this genomic research is to allow the 
identification of genetic factors that may influence the immunogenicity, safety, or tolerability of 
Ad26.ZEBOV and MVA-BN-Filo. Since the sample size is small, analysis will focus on 
validation of genes identified as possibly associated with these factors in previous (non-Ebola) 
studies and control of gene expression.
Optional blood samples for transcriptomics will be collected from subjects in Cohorts I and II (as 
part of the specific and additional immunogenicity assessments by the academic consortium 
partners, respectively, see
Table 5
and Table 6) and who consent separately to the 
transcriptomics component of the study. Blood samples will be collected at the specified time 
points (see Additional Time and Events Schedule). The goal is to assess the RNA transcriptome 
(gene expression) in a systems vaccinology approach to identify differentially expressed genes 
which relate to the immunologic and safety phenotype of the response to Ad26.ZEBOV and 
MVA-BN-Filo, and for analysis of antibody genes.
If subjects provide separate consent, leftover blood samples will be stored for possible future 
scientific/genetic research (see Section 16.2.5). Subjects can withdraw consent for their samples 
to be used for future research at any time.
Interim analyses may be performed as detailed in Section 11.6. The primary analysis will be 
performed when all subjects have completed the 6-month post-boost visit or discontinued earlier
and the clinical database is locked. This analysis will include 6-month post-boost safety and all 
available immunogenicity data up to this point. The final analysis will be performed when all 
subjects have completed the last study-related visit (see Section 10.1) or discontinued earlier. 
An IDMC will be commissioned for this study. Refer to Section 11.7 for details.
The sponsor halted all vaccinations in this study due to the occurrence of a serious and very rare 
condition, Miller Fisher syndrome, reported in the current study VAC52150EBL2001 (described 
in Section 1.1.2.3) until a revised ICF containing updated safety language was prepared and 
approval to restart the study was granted by the relevant competent authority. The study pause 
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VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
48
Approved, Date: 20 April 2017
interrupted dosing of subjects, some awaiting prime vaccination and some awaiting boost 
vaccination. When approval was granted in the UK to restart the study under Amendment 4, the 
sponsor offered a late boost vaccination to those subjects who did not receive it yet, unless 
participants had withdrawn from the trial or were not eligible to receive the boost. Vaccinated 
subjects have been following the same post-boost vaccination schedule as those subjects 
unaffected by the pause. Subjects who did not receive the late boost were encouraged to return 
for the 1-year post-prime visit. After restart of the study in the UK under Amendment 4, 
screening for Groups 1 and 2 restarted, but randomization to Group 3 was stopped to focus on 
the schedules for which an indication will be sought. After approval of Amendment 5, 
enrollment in the entire study will be stopped.
Subjects in the UK and France who reach the Day 365 visit prior to unblinding will be 
approached to consent 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 9.1.6 for details). After unblinding, only 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, 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. The parent(s)/legal guardian of 
children born to vaccinated female subjects who became pregnant with estimated conception 
within 28 days after vaccination with MVA-BN-Filo or within 3 months after vaccination with 
Ad26.ZEBOV, will also be approached to consent for enrollment of their offspring into the roll-
over study, according to the same rules that apply for the other subjects. Subjects in France who 
agree to continue the long-term follow-up after Day 365 and reach the Day 365 visit before the 
roll-over study is opened, will have further follow-ups in the current study until they have started 
in the roll-over study or for an additional 12 months [whichever comes first] or discontinued
earlier. These subjects will be contacted by telephone every 3 months after Day 365 (subjects 
will only visit the site when clinically indicated) for the collection of information on adverse 
events, serious adverse events, and IREs that were ongoing at the Day 365 visit, and to report 
and follow up on new serious adverse events, pregnancies, and IREs.
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. 
Due to significant delays in scheduled boost vaccinations caused by study pauses required for 
safety evaluations, enrollment in the entire study will not be resumed. Since many subjects in 
France have had no boost vaccinations and many subjects in the UK have had a late boost 
vaccination, it will be very difficult to evaluate the planned dosing regimens. Therefore, no 
further subjects will be recruited in the entire study (ie, UK and France). Additional data on the 
planned dosing regimens will be obtained from other studies. Vaccinated subjects in both 
countries will still be followed per protocol for safety.
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
49
Approved, Date: 20 April 2017
The elimination of one or more post-boost sampling time points for immunogenicity assessments 
may be considered to reduce blood sample volume in these subjects if preliminary findings 
suggest that these have no added informative value for the study.
Control and Blinding 
At study entry, subjects were offered the option to enroll into Cohorts I, II or III (as applicable). 
Within each cohort, subjects were randomized at baseline (on Day 1) in a 1:1:1 ratio to one of 
the 3 vaccination schedules (Groups 1, 2 and 3). All groups in Cohort I will receive an IM
injection with Ad26.ZEBOV and MVA-BN-Filo in an open-label fashion. The rationale for this 
cohort is to identify the peak of the B-cell response for the determination of the optimal sampling 
time points regarding B-cell responses as part of the additional immunogenicity assessments in 
Cohort II in the UK. Within each group in Cohorts II and III, subjects were randomized in a ratio 
indicated in Table 1 to receive the prime-boost vaccination with either Ad26.ZEBOV followed 
by MVA-BN-Filo, or placebo. Randomization (to vaccination schedule and to study vaccine) 
was used to minimize bias in the assignment of subjects to 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. Note that randomization to Group 3 was not resumed per Amendment 4 and that 
enrollment in entire study will be stopped per Amendment 5.
A placebo control will be used (in Cohorts II and III) to establish the frequency and magnitude of 
changes in clinical and immunologic endpoints that may occur in the absence of Ad26.ZEBOV 
and MVA-BN-Filo. Blind treatment will be used to reduce potential bias during data collection 
and evaluation of clinical safety endpoints. Blinding will be guaranteed by the 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 study vaccine 
administrator (see Definitions of Terms).
The rationale for defining the study as an observer-blind study is that the subjects and study-site
personnel will not be blinded to the vaccination schedule and no additional placebo injections 
will be administered to mask the regimens across groups; blinding will only mask the 
administration (and observations) of Ad26.ZEBOV, MVA-BN-Filo or placebo within 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 (nominal titer), 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.
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
50
Approved, Date: 20 April 2017
DNA Collection
An optional blood sample for DNA collection will be collected at baseline from subjects in 
Cohort II at selected sites and who consent separately to this component of the study. It is 
recognized that genetic variation can be an important contributory factor to interindividual 
differences in vaccine response (both safety and immunogenicity) and can also serve as a marker 
for disease susceptibility and prognosis. Genomic research in vaccine studies may help to explain 
interindividual variability in clinical and immunologic outcomes and may help to identify 
population subgroups that respond differently to a vaccine. The goal of the genomic component 
is to collect DNA to allow the identification of genetic factors that may influence the
immunogenicity, safety, or tolerability of Ad26.ZEBOV and MVA-BN-Filo. DNA samples may 
be used to help address emerging issues and to enable the development of safer, more effective
vaccines. Since the sample size is small, analysis will focus on validation of genes identified as 
possibly associated with these factors in previous (non-Ebola) studies and control of gene 
expression. 
Transcriptomics
Optional blood samples for transcriptomics will be collected at the specified time points from 
subjects in Cohorts I and II and who consent separately to the transcriptomics component of the 
study. The goal is to assess the RNA transcriptome (gene expression) in a systems vaccinology 
approach to identify differentially expressed genes which relate to the immunologic and safety 
phenotype of the response to Ad26.ZEBOV and MVA-BN-Filo (taking advantage of the rich 
phenotypic data being collected in the safety, and cellular and humoral immunologic studies) and 
for analysis of antibody genes.
Future Research
If subjects provide separate consent, leftover blood samples will be stored for possible future 
scientific/genetic 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 can withdraw consent for their samples to be 
used for future research at any time.
4.
SUBJECT POPULATION
Screening of subjects for eligibility was performed within 12 weeks before administration of the 
study vaccine on Day 1. 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.
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
51
Approved, Date: 20 April 2017
4.1.
Inclusion Criteria
Each potential subject must satisfy all of the following criteria to be enrolled in the study. 
1.
Signed an ICF indicating that he/she understands the purpose of, and procedures 
required for, the study and is willing to participate in the study. 
2.
Man or woman, between 18 and 65 years of age, inclusive, at randomization.
3.
Healthy in the investigator’s clinical judgment on the basis of medical history, 
physical examination, ECG, and vital signs performed at screening. 
4.
Criterion modified per Amendment 4
4.1.
Healthy on the basis of clinical laboratory tests performed at screening. If the results 
of the laboratory screening tests are outside the normal reference ranges, the subject 
may be included only if the investigator judges the abnormalities or deviations from 
normal to be not clinically significant or to be appropriate and reasonable for the 
population under study. This determination must be recorded in the subject's source 
documents and initialed by the investigator.
Note: The safety laboratory assessments at screening are to be performed within 
28 days prior to the prime vaccination on Day 1 (including Day 1 before vaccination) 
and may be repeated if they fall outside this time window.
Note: In case of menstruation, urinalysis must be postponed but a result should be 
available before the prime vaccination.
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.
5.
Criterion modified per Amendment 4
5.1.
Contraceptive use by men and women should be consistent with local regulations 
regarding the use of contraceptive methods for subject participating in clinical studies.
Before randomization, a woman must be either:

Of childbearing potential and practicing (or intending to practice) 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 (IUD) or intrauterine system (IUS); 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); true abstinence (when this is in 
line with the preferred and usual lifestyle of the subject); OR
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
52
Approved, Date: 20 April 2017

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 IU/L or 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 of childbearing potential changes (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.
Woman of childbearing potential must have a negative serum (-human chorionic 
gonadotropin [-hCG]) at screening and a negative urine -hCG pregnancy test 
immediately prior to each study vaccine administration.
7.
Man who is sexually active with a woman of childbearing potential and has not had a 
vasectomy performed more than 1 year prior to screening must be willing to use 
condoms for sexual intercourse beginning prior to enrollment.
8.
Available and willing to participate for the duration of the study and follow-up visits.
9.
Willing and able to comply with the protocol requirements, including the prohibitions 
and restrictions specified in Section 4.3.
10.
Willing to provide verifiable identification.
11.
Having a means to be contacted.
12.
Having coverage by a social security insurance (for sites in France) and allowing use 
and storage of National Insurance Number on The Over-volunteering Prevention 
System (TOPS) database and bank account information for purposes of 
reimbursement (for sites in UK).
4.2.
Exclusion Criteria
Any potential subject who meets any of the following criteria will be excluded from participating 
in the study. 
1.
Having received any candidate Ebola vaccine.
2.
Diagnosed with Ebola virus disease, or prior exposure to Ebola virus, including travel 
to West Africa less than 1 month prior to screening. West Africa includes but is not 
limited to the countries of Guinea, Liberia, Mali, and Sierra Leone.
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.
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
53
Approved, Date: 20 April 2017
3.
Having received any experimental candidate Ad26- or MVA-based vaccine in the 
past.
Note: Receipt of any approved vaccinia/smallpox vaccine or experimental Ad-vector 
vaccine other than Ad26 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; and tris (hydroxymethyl)-amino methane (THAM) for 
MVA-BN-Filo vaccine]), including known allergy to egg, egg products, and 
aminoglycosides.
5.
Presence of acute illness (this does not include minor illnesses such as diarrhea or 
mild upper respiratory tract infection) or temperature ≥38.0ºC on Day 1. Subjects with 
such symptoms will be excluded from enrollment at that time, but may be rescheduled 
for enrollment at a later date.
6.
Positive hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody at 
screening.
7.
HIV type 1 or type 2 infection.
8.
Pregnant, breast-feeding, or planning to become pregnant while enrolled in this study 
until at least 3 months after the prime vaccination or up to 1 month after the boost 
vaccination (whichever takes longer).
9.
Presence of significant conditions or clinically significant findings during screening of 
medical history, physical examination, ECG, 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.
10.
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. 
11.
History of malignancy other than squamous cell or basal cell skin cancer, unless there 
has been surgical excision, that is considered cured.
12.
Major surgery (per the investigator’s judgment) within the 4 weeks prior to screening, 
or planned major surgery during the study (from the start of screening onwards).
13.
Post-organ 
and/or 
stem 
cell 
transplant 
whether 
or 
not 
with 
chronic 
immunosuppressive therapy.
14.
Received any disallowed therapies as noted in Section 8 before the planned first
administration of the prime vaccine on Day 1.
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
54
Approved, Date: 20 April 2017
15.
Received an investigational drug or investigational vaccines 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.
16.
Donation of a unit of blood within 12 weeks before Day 1 or plans to donate blood 
during participation in the study (from the start of screening onwards).
17.
Receipt of blood products or immunoglobulin within 3 months prior to screening and 
during participation in the study.
18.
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. 
19.
History of chronic urticaria (recurrent hives).
20.
Unable to communicate reliably with the investigator.
21.
Unlikely to adhere to the requirements of the study in the opinion of the investigator.
22.
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. Site staff, or their family 
members, may be enrolled provided this is governed by institutional procedures and 
that there is no direct involvement in the proposed study or relationship with the 
investigator.
23.
Under legal guardianship or incapacitation.
NOTE: Investigators should ensure that all study enrollment criteria have been met at screening. 
If a subject's clinical status changes (including any available laboratory results or receipt of 
additional medical records) after screening but before the prime vaccination on Day 1 such that 
he/she no longer meets all 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.
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
55
Approved, Date: 20 April 2017
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.
Woman 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 woman of childbearing potential changes (eg, 
woman who is not heterosexually active becomes active), she must begin a highly 
effective method of birth control, as described above in Section 4.1, until at least 
3 months after the prime vaccination or up to 1 month after the boost vaccination 
(whichever takes longer). *
Note: A period of 3 months after vaccination with Ad26.ZEBOV and 1 month after 
vaccination with MVA-BN-Filo should be respected. 
Note: Prior to each study vaccine administration, a urine pregnancy test should be 
performed for women of childbearing potential.
2.
Woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted 
reproduction from the start of screening onwards until at least 3 months after the 
prime vaccination or up to 1 month after the boost vaccination (whichever takes 
longer). *
3.
Man who has not had a vasectomy performed more than 1 year prior to screening and 
is sexually active with a woman 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), and must also not donate sperm 
from the start of screening onwards until at least 3 months after the prime vaccination 
or up to 1 month after the boost vaccination (whichever takes longer). *
*After unblinding for the primary analysis, placebo subjects may stop birth 
control measures or resume their pre-study birth control measures, and may 
donate eggs (women) or sperm (men).
4.
Woman 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).
5.
Not travel to epidemic Ebola areas while enrolled in the study from the start of 
screening onwards until the 42-day post-boost visit. Subjects who traveled to these 
areas should have returned at least 1 month before the long-term follow-up visits 
(6 months post-boost and Day 365). 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 in Section 4.2.)
6.
Not use any disallowed concomitant therapies as described in Section 8.
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5.
TREATMENT ALLOCATION AND BLINDING
Vaccine Schedule and Study Vaccine Allocation
Based on subject’s availability and informed consent, a subject was enrolled in one of 3 cohorts
at study entry. Central randomization was implemented in this study. At baseline, subjects were
randomly assigned to 1 of 3 groups in a 1:1:1 ratio in Cohorts I, II, and III, and within groups 
randomly assigned to Ad26.ZEBOV and MVA-BN-Filo, or placebo in a 14:1 and 10:3 ratio in 
Cohorts II and III, respectively, based on a computer-generated randomization schedule prepared 
before the study by or under the supervision of the sponsor. The randomization within each 
group was balanced by using randomly permuted blocks and was stratified by country in 
Cohorts II and III. Randomization in each group (for Cohorts II and III) was stratified further 
according to age at randomization (≤50 years, >50 years), with at least 20% (of the total of both 
cohorts) of subjects in the >50 years category. Note that randomization to Group 3 was not 
resumed per Amendment 4 and that enrollment in the entire study will be stopped per 
Amendment 5. The interactive web response system (IWRS) assigned a unique code, which 
dictated 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.
Blinding
Blinding procedures are not applicable for Cohort I (as all subjects will receive Ad26.ZEBOV 
and MVA-BN-Filo in an open-label fashion).
In Cohorts II and III, subjects and study-site personnel will be blinded to the study vaccine 
allocation within groups until the last subject of the study completes the 6-month post-boost visit 
or discontinues earlier and the clinical database is locked, except for unblinded qualified study-
site personnel with primary responsibility for study vaccine preparation and dispensing, and not 
involved in any other study-related procedure. The study vaccines will be administered by a 
study vaccine administrator (see Definitions of Terms).
In Cohorts II and III, sponsor personnel will be blinded to study vaccine allocation within groups 
until all subjects of the study have their 6-month post-boost visit or discontinue earlier and the 
clinical database is locked. At that time, the subjects enrolled in the study will be unblinded and 
the subjects who received placebo will be contacted by the site to communicate that they have 
completed the study and no further follow-up is required. However, subjects who received 
placebo and reach the Day 365 visit prior to unblinding will be required to attend the Day 365 
visit. After unblinding, only subjects who received Ad26.ZEBOV or MVA-BN-Filo will be 
followed up in an open-label fashion until the Day 365 visit. The primary analysis will be 
performed when all subjects in the study have completed the 6-month post-boost visit or 
discontinued earlier and the clinical database is locked. In case interim analyses will be 
performed, study-site personnel (except for those with primary responsibility for study vaccine 
preparation and dispensing), the sponsor (except for programming, statistics, clinical and clinical 
immunology personnel involved in the analysis, and the sponsor committee involved in making 
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future decisions for the program) and subjects will remain blinded to study vaccine allocation 
until the primary analysis (see below).
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 (in case of a medical emergency requiring unblinding).
Data that may potentially unblind the study vaccine assignment (ie, antibodies to study vaccine, 
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 Definitions of Terms and Section 17.8).
Under normal circumstances, the blind should not be broken until the primary analysis. 
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.
In general, randomization codes will be disclosed fully for the study only if all subjects in the 
study completed the 6-month post-boost visit (or discontinued earlier) and the clinical database is 
locked. However, if an interim analysis is specified, the randomization codes and, if required, the 
translation of randomization codes into treatment and control groups will be disclosed to those 
authorized and only for those subjects included in the interim analysis.
If the randomization code is broken by the investigator or the study-site personnel, the subject 
must discontinue study vaccine and must be followed as appropriate (see Section 10.2 for further 
details). If the randomization code is broken by the sponsor for safety reporting purposes, the 
subject should not discontinue study vaccine and may remain in the study (if the randomization 
code is still blinded to the study-site personnel and subject).
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6.
DOSAGE AND ADMINISTRATION
An overview of the study vaccination schedules is provided in Table 2. 
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 1.9x108 Inf.U per dose (range 1.27 to 
2.67 x108 Inf.U), supplied in a single use vial (0.5 mL extractable);
Placebo: 0.9% saline, 0.5 mL extractable.
Ad26.ZEBOV and MVA-BN-Filo, or placebo, will be administered as 0.5-mL IM injections into 
the deltoid, by a study vaccine administrator (see Definitions of Terms). 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), per exclusion criterion #9 in Section 4.2. In each subject, 
the boost vaccination should be administered in the opposite deltoid from the prime vaccination 
(unless the opposite arm has a condition that prevents evaluating the arm after injection) and it 
should be recorded in the CRF in which arm the vaccination has been administered. No local or 
topical anesthetic will be used prior to the injection.
Discontinuation of study vaccine administration should occur in any subject meeting the criteria 
outlined in Section 10.2. Criteria for postponement of vaccination at the scheduled time for 
vaccine administration and contraindications to boost vaccination have been defined in 
Sections 6.2 and 6.3, respectively. Refer to Section 9.2.3 for details on the pre-specified pausing 
rules to halt vaccination of further subjects.
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 (eg, in case of grade 3 adverse events). 
The Site Investigational Product Procedures Manual specifies the maximum time that will be 
allowed between preparation and administration of the study vaccine. For storage conditions, 
please refer to Section 14.3.
6.2.
Criteria for Postponement of Vaccination
A subject will not be given the prime or boost 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);
Fever (body temperature ≥38.0°C) at the time of vaccination.
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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 vaccination is postponed, the timing of the post-boost visits will be 
planned relative to the actual vaccination day (see Section 9.1.1).
6.3.
Contraindications to Boost Vaccination
A subject will not be given the boost vaccination if he/she experiences any of the following 
events at any time after the prime vaccination: 
1. Anaphylaxis clearly attributable to vaccination with the study vaccine; OR
2. Generalized urticaria within 72 hours of vaccination considered to be at least possibly related 
to the study vaccine; OR
3. A serious adverse event considered to be at least possibly related to the study vaccine; OR
4. A severe (grade 3) (non-serious) adverse event considered to be at least possibly related to 
the study vaccine that persists for 3 or more days, or a severe (grade 3) (non-serious) 
laboratory abnormality (including unexplained hematuria) considered to be at least possibly 
related to the study vaccine; OR
5. Injection site ulceration, abscess or necrosis considered to be at least possibly related to the 
study vaccine; OR
6. 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.
7.
TREATMENT COMPLIANCE
All study vaccines will be administered on site by a study vaccine administrator (see Definitions 
of Terms). The date and time of each study vaccine administration will be recorded in the CRF.
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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 boost 
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.
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 4.1.
Subjects are allowed to receive all routine immunizations according to local schedules, taking 
into consideration the following restrictions. These routine immunizations should be 
administered at least 15 days before (or at least 15 days 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 events. Vaccination with live attenuated vaccines is 
prohibited in the period from 30 days before Day 1 (prime vaccination) to 30 days after the boost 
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 non-steroidal anti-inflammatory drugs (NSAIDs) may be 
used post-vaccination only in case of medical need (eg, body temperature ≥38.5°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.
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.
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9.
STUDY EVALUATIONS
9.1.
Study Procedures
Overview
9.1.1.
The Time and Events Schedule and Additional Time and Events Schedule summarize 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.
In summary, safety will be evaluated in all subjects from the 3 cohorts. In Cohort I (in the UK), 
only plasmablast response kinetics (and transcriptomics in subjects who consented separately) 
will be evaluated in addition to the safety assessments. In Cohorts II and III in both countries,
core immunogenicity assessments (humoral and cellular assays) will be performed. In Cohort II
in both countries, additional immunogenicity assessments will be done.
Visit Windows
The screening visit had to be performed within 12 weeks prior to the baseline visit (ie, the day of 
the subject’s prime vaccination, Day 1). Visit windows that will be allowed are summarized in 
Table 3. The subject should be encouraged to come in the exact day planned and use the visit 
window only if absolutely necessary. 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
and Additional Time and Events Schedule) will be determined relative to the actual day of 
vaccination.
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Table 3:
Visit Windows
Visit Description
Group 1
Group 2
Group 3
Allowed Window 
Prime Vaccination
Day 1
Day 1
Day 1
-
One Day Post-Prime – Cohort II only
Day 2 
Day 2 
Day 2 
±1 day
Three Days Post-Prime 
Day 4 
Day 4 
Day 4 
±1 day
Seven Days Post-Prime
Day 8 
Day 8 
Day 8 
±1 day
Eight Days Post-Prime – Cohort I only
Day 9 
Day 9 
Day 9 
±1 day
Ten Days Post Prime – Cohort I only
Day 11 
Day 11 
Day 11 
±1 day
Twelve Days Post-Prime – Cohort I only
Day 13 
Day 13 
Day 13 
±1 day
Fourteen Days Post-Prime – Cohorts I and II and 
Group 3 in Cohort III only
Day 15
Day 15
Day 15
±1 day
To be determineda – Cohort II only
Day x
Day x
Day x
±1 day
Boost Vaccination 
Day 29 
Day 57 
Day 85
±1 day
One Day Post-Boost – Cohort II only
Day 30 
Day 58 
Day 86
±1 day
Three Days Post-Boost 
Day 32 
Day 60 
Day 88
±1 day
Five Days Post-Boost – Cohort I only
Day 34 
Day 62 
Day 90
±1 day
Seven Days Post-Boost 
Day 36 
Day 64 
Day 92
±1 day
Nine Days Post-Boost – Cohort I only
Day 38 
Day 66 
Day 94
±1 day
Fourteen Days Post-Boost – Cohort II only
Day 43 
Day 71 
Day 99
±1 day
To be determineda – Cohort II only
Day x
Day x
Day x
±1 day
Twenty-one Days Post-Boost
Day 50 
Day 78
Day 106
±3 days
Forty-two Days Post-Boostb
Day 71
Day 99 
Day 127
±3 days
Follow-up (6 months post-boost)c,d
Day 209
Day 237
Day 265
±30 days
Follow-up (1 year post-prime)c,e
Day 365 
Day 365 
Day 365 
±30 days
Note: If a subject did not receive study vaccine on the planned day of vaccination, the timings of the next visits 
post-vaccination will be determined relative to the actual day of vaccination. 
a At plasmablast peak time point determined in Cohort I (only applies to Cohort II in the UK).
b The 42-days post-boost visit may be replaced by a telephone call if the subject is not able to come to the site (only 
applies to Cohort I in the UK and Cohort II in the UK and France).
c The 6-month post-boost and Day 365 visits may be replaced by a telephone call if the subject is not able to come 
to the site (only applies to Cohort I in the UK).
d Subjects who already attended the 6-month post-prime visit (which has been replaced with the 6-month post-boost 
visit per protocol amendment 3) will be required to also attend the 6-month post-boost visit.
e Subjects in France who agree to continue the long-term follow-up after Day 365 and reach the Day 365 visit before 
the roll-over study VAC52150EBL4001 is opened, will have further follow-ups in the current study until they 
have started in the roll-over study or for an additional 12 months (whichever comes first) or discontinued earlier.
These subjects will be contacted by telephone every 3 months after Day 365 (subjects will only visit the site when 
clinically indicated).
Blood Sampling Volumes
For subjects with core as well as exploratory immunogenicity assessments, less than 500 mL of 
blood will be drawn over each 60-day interval throughout the study, which is within the limits of 
standard blood donation.
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.
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Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples.
Screening Phase
9.1.2.
Up to 12 weeks before baseline (the day of the subject’s prime vaccination, Day 1) and after 
signing and dating the ICF (see Section 16.2.3), screening assessments as indicated in the Time 
and Events Schedule were performed. Screening could be split into multiple days or visits. In 
exceptional cases, the screening phase could be extended if discussed with and approved 
(documented) by the sponsor, eg, if not all the test results became available during the allocated 
12 weeks; this was evaluated on a case-by-case basis. Subjects whose screening period was 
longer than the protocol-defined 12 weeks as a result of a pause were allowed to rescreen once.
For men and for women of non-childbearing potential, there was no minimum duration of the 
screening phase and it lasted only for the time required to verify eligibility criteria. For women 
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 pregnancy test immediately prior to each study vaccination (see 
Sections 4.1 and 4.2). All men and women, except for women 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 healthy subjects complying with the criteria specified in Section 4 were included in the 
study. The investigator provided detailed information on the study to the subject and obtained
written informed consent prior to each subject’s study participation. The procedures indicated in 
the Time and Events Schedule and Additional Time and Events Schedule were only performed 
after the subject’s written informed consent had been obtained. 
The following was 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 (at any time prior to study entry), and concomitant therapies;
Serum pregnancy test (for women of childbearing potential);
Blood sampling for hematology and chemistry (fasting or non-fasting) and troponin I;
Urine sampling for urinalysis (dipstick);
Serology testing (HIV type 1 or type 2, hepatitis B, hepatitis C);
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);
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Full physical examination (including height and body weight);
ECG recording;
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 was assessed once all screening 
values and results of any other required evaluations were available. Retesting of values (eg, 
safety laboratory) that lead to exclusion was allowed once using an unscheduled visit during 
screening to assess eligibility, also for subjects who were rescreened due to a pause. The safety 
laboratory assessments (ie, serum chemistry and hematology, troponin I testing, serology, 
pregnancy testing, urinalysis) were to be performed within 28 days prior to the prime vaccination 
and might be repeated if they fall outside this time window. Similarly, subjects who were
rescreened due to a pause had to have new safety laboratory assessments within 28 days of the 
prime vaccination. Study subjects who qualified for inclusion were contacted and scheduled for 
enrollment and prime vaccination within 12 weeks.
Note that enrollment will be stopped per Amendment 5.
Vaccination Phase
9.1.3.
Prime Vaccination - Day 1 (All Groups)
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 the initial laboratory sampling 
occurred more than 12 weeks before baseline (Day 1), sampling will need to be repeated. 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 eligibility criteria, then the subject should be excluded from further 
participation in the study. 
A urine pregnancy test (for women of childbearing potential), vital signs measurements, blood 
sampling for hematology and chemistry (fasting or non-fasting), and an abbreviated, symptom-
directed physical examination (as indicated by the investigator) will be performed. The eligible 
subjects will be allocated (by central randomization) to a vaccination schedule as described in 
Section 5 and will receive the prime vaccination via IM injection as described in Section 6,
unless any of the pre-specified criteria not to proceed with vaccination are met (see Sections 6.2
and 10.2 for details) or if a pause for vaccination of further subjects has been installed (see 
Section 9.2.3).
Blood samples for core immunogenicity assessments in Cohorts II and III will be collected 
before the prime vaccination as indicated in the Time and Events Schedule and Section 9.3.2. 
Blood samples for additional immunogenicity assessments in Cohort II and for specific 
immunogenicity assessments in Cohort I will be collected as indicated in the Additional Time 
and Events Schedule and Section 9.3.2.
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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 study vaccine to a 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 and pregnancies will be collected and documented on 
the CRF, together with the information on any concomitant therapies. 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 solicited local adverse events and body temperature. Subjects will also
record symptoms of solicited local and systemic adverse events in the diary in the evening after 
vaccination and then daily for the next 7 days. Subjects will be instructed to notify the 
investigator immediately for any unsolicited adverse event (not listed on the diary card) or for 
any severe (grade 3) solicited adverse event (listed on the diary card).
Boost Vaccination - Day 29 (Group 1), Day 57 (Group 2), Day 85 (Group 3)
The subjects will receive the boost vaccination via IM injection as described in Section 6, unless 
any of the pre-specified criteria not to proceed with vaccination are met (see Sections 6.2, 6.3, 
and 10.2 for details) or if a pause for vaccination of further subjects has been installed (see 
Section 9.2.3).
Before the boost vaccination, a urine pregnancy test (women of childbearing potential), ECG and 
vital sign measurements, blood sampling for hematology and chemistry (fasting or non-fasting), 
and an abbreviated, symptom-directed physical examination (as indicated by the investigator)
will be performed. 
Blood samples for core immunogenicity assessments in Cohorts II and III will be collected 
before the boost vaccination as indicated in the Time and Events Schedule and Section 9.3.2. 
Blood samples for additional immunogenicity assessments in Cohort II and for specific 
immunogenicity assessments in Cohort I will be collected as indicated in the Additional Time 
and Events Schedule and Section 9.3.2.
The same procedures are applicable as for the prime vaccination regarding vaccine preparation;
collection of adverse events, serious adverse events, IREs and pregnancies, together with the
information on concomitant therapies; and procedures for subjects after discharging.
Post-vaccination Phase 
9.1.4.
The subjects will come to the site at 3 and 7 days after each vaccination and also at 21 and 
42 days after the boost vaccination as indicated in the Time and Events Schedule. In Cohorts I 
and II, the subjects will come to the site for additional post-vaccination visits as indicated in the 
Additional Time and Events Schedule. The 42-days post-boost visit (Cohorts I and II) may be 
replaced by a telephone call if the subject is not able to come to the site.
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The subject’s diary will be reviewed by study-site personnel at 3 and 7 days after each 
vaccination. The investigator will examine the injection site for occurrences of erythema, 
induration/swelling, and pain/tenderness, and will ask if itching at the injection site occurred at 
these visits in order to complete the relevant parts of the CRF. 
Blood sampling for hematology and chemistry (fasting or non-fasting) at 7 days after each 
vaccination and an abbreviated, symptom-directed physical examination (as indicated by the 
investigator) will be performed. An ECG will be recorded at 7 days after the boost vaccination. 
Adverse events, serious adverse events and pregnancies will be collected and documented on the 
CRF, together with the information on any concomitant therapies. For reporting of IREs, refer to 
Section 12.3.3.
Blood samples for core immunogenicity assessments in Cohorts II and III will be collected as 
indicated in the Time and Events Schedule and Section 9.3.2. Blood samples for additional 
immunogenicity assessments in Cohort II and for specific immunogenicity assessments in 
Cohort I will be collected as indicated in the Additional Time and Events Schedule and
Section 9.3.2.
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. 
Open-label Long-term Follow-up Phase
9.1.5.
When all subjects have had their 6-month post-boost visit (Day 209 in Group 1; Day 237 in 
Group 2; Day 265 in Group 3) or discontinued earlier and the clinical database is locked, the 
subjects will be unblinded. After unblinding, only subjects who received Ad26.ZEBOV or 
MVA-BN-Filo will be followed up in an open-label fashion until the Day 365 visit. Subjects who 
received placebo will be contacted by the site to communicate that they have completed the 
study and no further follow-up is required. However, subjects who received placebo and reach 
the Day 365 visit prior to unblinding will be required to attend the Day 365 visit. The 6-month
post-boost and Day 365 visits (Cohort I) may be replaced by a telephone call if the subject is not 
able to come to the site.
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.
Blood samples for core immunogenicity assessments in Cohorts II and III will be collected at 
both visits as indicated in the Time and Events Schedule and Section 9.3.2. In Cohort II,
follow-up blood samples will be collected for additional immunogenicity assessments on the 
6-month post-boost visit as indicated in the Additional Time and Events Schedule and 
Section 9.3.2.
Subjects in France who agree to continue the long-term follow-up after Day 365 and reach the 
Day 365 visit before the roll-over study VAC52150EBL4001 (see Section 9.1.6) is opened, will 
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have further follow-ups in the current study until they have started in the roll-over study or for an 
additional 12 months (whichever comes first) or discontinued earlier. These subjects will be 
contacted by telephone every 3 months after Day 365 (subjects will only visit the site when 
clinically indicated) for the collection of information on adverse events, serious adverse events, 
and IREs that were ongoing at the Day 365 visit, and to report and follow up on new serious 
adverse events, pregnancies, and IREs.
VAC52150 Vaccine Development Roll-over Study
9.1.6.
Subjects in the UK and France who reach the Day 365 visit prior to unblinding will be 
approached to consent 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 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, 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. The parent(s)/legal guardian of children born to vaccinated 
female subjects who became pregnant with estimated conception within 28 days after 
vaccination with MVA-BN-Filo or within 3 months after vaccination with Ad26.ZEBOV, will 
also be approached to consent for enrollment of their offspring into the roll-over study, according 
to the same rules that apply for the other subjects.
9.2.
Safety Evaluations
Safety Endpoints
9.2.1.
Primary Endpoints:

Adverse events, collected from signing of the ICF onwards until the 42-day post-boost visit 
(Day 71 in Group 1; Day 99 in Group 2; and Day 127 in Group 3).

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) until 7 days after each study 
vaccine administration.
Safety Assessments 
9.2.2.
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 boost
vaccination must be recorded on the Adverse Event section of the CRF. Thereafter, reporting 
will be limited to all serious adverse events. 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. Refer to Section 9.1.5 for more information for subjects in France 
who have further follow-ups from Day 365 onwards until the roll-over study is opened. 
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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 9.2.3 have been met. 
An IDMC will be appointed by the sponsor with recommendations from the Clinical Steering 
Committee (see Section 11.8) 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 11.7.
Adverse Events
All adverse events, whether serious or non-serious, will be reported by the subject from signing 
of the ICF onwards until the 42-day post-boost visit. 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 study vaccine administration. Adverse events will be followed by the 
investigator as specified in Section 12. Refer to Section 9.1.5 for more information for subjects 
in France who have further follow-ups from Day 365 onwards until the roll-over study is opened.
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 study vaccine
administration and again at 60 (±15) minutes post-vaccination, 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 record symptoms of solicited local and systemic adverse 
events in the diary in the evening after each study vaccine administration and then daily for the 
next 7 days (until Day 8) to serve as a reminder to the subject for the next visit. On Day 8, 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 and document the relevant information in 
the clinic chart. 
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 study vaccine administration and then daily for the next 7 days in the diary. 
Solicited Systemic Adverse Events
Subjects will be instructed on how to record daily temperature using a thermometer provided for 
home use. Subjects should record the body temperature in the evening after each study vaccine
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administration and then daily for the next 7 days in the diary. 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 
study vaccine administration and then daily for the next 7 days in the diary: 
nausea/vomiting 
myalgia
fatigue/malaise
fever
headache
arthralgia
chills
If a solicited local or systemic adverse event is not resolved on Day 8, the follow-up will be 
captured in 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, an ECG and troponin I 
test should be obtained and the subject should be referred to a local cardiologist. 
Clinical Laboratory Tests 
Blood samples for serum chemistry and hematology and for troponin I, serology and pregnancy 
testing (~15 mL) and a urine sample for urinalysis (dipstick) will be collected at screening. 
Blood samples for serum chemistry and hematology (~7 mL) will also be taken at additional 
time points as indicated in the Time and Events Schedule. Samples can be taken in fasting or 
non-fasting conditions but should be documented in the CRF. 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 up to the 42-day post-boost visit.
Thereafter, only serious adverse events need to be recorded. The laboratory reports must be filed 
with the source documents. For reporting of IREs, refer to Section 12.3.3.
The following tests will be performed by the central laboratory. Parameters marked with an 
asterisk (*) will only be measured at screening:

Hematology and Coagulation Panel 
- hemoglobin
- fibrinogen*
- white blood cell (WBC) count with differential- prothrombin time
- platelet count
- activated partial thromboplastin time
Blood smear: A WBC evaluation may include any abnormal cells, which will then be reported by 
the laboratory. A hematology evaluation may include abnormalities in the red blood cell (RBC) 
count and/or RBC parameters and/or RBC morphology, which will then be reported by the 
laboratory. In addition, any other abnormal cells in a blood smear will also be reported. Only 
clinically significant abnormal WBC, abnormal RBC, or any other abnormal cells in a blood smear 
will be reported as adverse events.
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
Serum Chemistry Panel 
- sodium
- total protein*
- potassium
- total bilirubin*
- blood urea nitrogen (BUN)
- creatinine
- aspartate aminotransferase (AST)
- FSH* 
(only in women >45 years of age with 
amenorrhea <2 years or ≤45 years of age 
with amenorrhea >6 months)
- alanine aminotransferase (ALT)
- glucose (fasting or non-fasting)*
- albumin*

Urinalysis – Dipstick for:
- glucose*
- protein*
- ketones*
- blood*
In case of positive urinalysis dipstick results, the sediment will be examined microscopically (only 
RBC will be documented).
Additional clinical laboratory assessments to be performed by the central laboratory (unless 
otherwise specified) are as follows:

Serum pregnancy test for women of childbearing potential at screening;

Urine pregnancy test for women of childbearing potential before each study vaccination (by 
the local laboratory);

Serology (HIV type 1 and type 2 antibody, HBsAg, and HCV antibody) at screening;

Troponin I testing at screening.
Laboratory values will be determined according to the toxicity grading tables in Attachment 1 if 
applicable for laboratory tests.
Any clinically significant abnormalities occurring from signing of the ICF onwards until 42 days 
after the boost vaccination must be recorded on the Adverse Event section of the CRF. 
Thereafter, reporting will be limited to all serious adverse events. All events should be followed 
(by repeat testing) to resolution, or until reaching a clinically stable endpoint. For reporting of 
IREs, refer to Section 12.3.3.
Electrocardiogram 
A single, 12-lead ECG will be performed at the time points indicated in the Time and Events 
Schedule and interpreted locally. Additional ECG monitoring may be done at other time points 
during the study if clinically indicated based on signs and symptoms.
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 for the same time point as ECG recording, the procedures 
should be performed in the following order: vital signs, ECG(s), blood draw.
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Any clinically significant abnormalities occurring from signing of the ICF onwards until 42 days 
after the boost vaccination must be recorded on the Adverse Event section of the CRF. 
Thereafter, reporting will be limited to all serious adverse events. All events should be followed 
to resolution, or until reaching a clinically stable endpoint. For reporting of IREs, refer to 
Section 12.3.3.
Vital Signs (blood pressure, pulse/heart rate and body temperature)
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.
Body temperature will be assessed at screening and prior to study vaccine administration at the 
site. In addition, subjects will measure and record body temperature at home in the diary (see 
Solicited Systemic Adverse Events).
Any clinically significant abnormalities occurring from signing of the ICF onwards until 42 days 
after the boost vaccination must be recorded on the Adverse Event section of the CRF. 
Thereafter, reporting will be limited to all serious adverse events. All events should be followed 
to resolution, or until reaching a clinically stable endpoint. For reporting of IREs, refer to 
Section 12.3.3.
Physical Examination 
A full physical examination, including height and body weight, will be performed by the 
investigator at screening. At other visits, an abbreviated, symptom-directed physical examination 
will be performed as indicated by the investigator 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.
A full physical examination includes the following: general appearance, eyes, ears, nose, throat, 
cardiovascular system, respiratory system, gastrointestinal system, and skin and mucous 
membranes. 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 inspection of the vaccination site(s).
The height should be measured barefooted at the screening visit. To obtain the actual body 
weight, subjects must be weighed lightly clothed.
Any clinically significant abnormalities occurring from signing of the ICF onwards until 42 days 
after the boost vaccination must be recorded on the Adverse Event section of the CRF. 
Thereafter, reporting will be limited to all serious adverse events. All events should be followed 
to resolution, or until reaching a clinically stable endpoint. For reporting of IREs, refer to 
Section 12.3.3.
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Pausing Rules
9.2.3.
The investigators and the sponsor’s medical monitor will review the safety of enrolled subjects 
on an ongoing basis. The sponsor’s medical monitor will be involved in all discussions and 
decisions (see Section 12.4).
If any of the following events occur in any subject who received at least one dose of study 
vaccine in the study (at any site), that site investigator will halt the vaccination of further subjects 
and the sponsor’s medical monitor will be notified immediately. The sponsor’s medical monitor 
will then also inform all the other investigators to halt further vaccination as well.
1. Death in any subject considered at least possibly related to the study vaccine; OR
2. An anaphylactic reaction within 24 hours of vaccination or the presence of generalized 
urticaria within 72 hours of vaccination in any subject considered at least possibly related to 
the study vaccine; OR
3. A life-threatening or other serious adverse event in any subject considered at least possibly 
related to the study vaccine.
If any of the following events occur in subjects who received at least one dose of study vaccine 
in the study (across all sites), the sponsor’s medical monitor will notify all investigators to halt 
vaccination of further subjects.
4. Three or more subjects experience a severe (grade 3) (non-serious) unsolicited adverse event 
(of the same type) considered to be related to any of the study vaccines that persists for 3 or 
more days; OR
5. Three or more subjects experience a persistent (upon repeat testing) severe (grade 3) 
(non-serious) abnormality (including unexplained hematuria) related to the same laboratory 
parameter and considered to be related to any of the study vaccines; OR
6. Three or more subjects experience the same severe (grade 3) (non-serious) solicited systemic 
reaction considered to be related to any of the study vaccines that persists for 3 or more days 
(subjective systemic reaction corroborated by study personnel).
For the events described above, the sponsor’s medical monitor notifies 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. If 
any pausing rule is met, and following the IDMC review it is deemed appropriate to restart 
dosing, a request to restart dosing with pertinent data must be submitted to health authorities as a 
request for a substantial amendment. Dosing can restart only after approval of a substantial 
amendment by the competent authority. 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. The communications from 
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the IDMC will be forwarded by the investigator to the Independent Ethics Committee 
(IEC)/Institutional Review Board (IRB) according to local standards and regulations and by the 
sponsor to relevant health authorities. 
9.3.
Immunogenicity Evaluations
Immunogenicity Endpoints
9.3.1.
Secondary Endpoints:
Humoral immune response

Binding antibody levels elicited by vaccination using EBOV GP ELISA at 21 days post
boost.
Exploratory Endpoints:
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 at selected time 
points:
Humoral immune response

Binding antibody levels elicited by vaccination using EBOV GP ELISA at other relevant 
time points.

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 Ad26 and/or MVA vector in ELISA 
and/or neutralization assays and against EBOV isolate in a neutralization test, if assays are 
available.

Humoral immune responses to different EBOV GPs and/or filovirus GPs and/or TAFV NP, 
if assays are available.

Molecular and functional characterization of study vaccine-elicited antibodies, which may 
include, but will not be limited to: kinetic studies, repertoire analysis, Fc characterization, 
isotype analysis and epitope mapping, if assays are available.
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 (intracellular cytokine staining [ICS]) after EBOV GP-
specific stimulation of fresh and/or frozen PBMC (including, but not limited to, IFN-, 
interleukin [IL]-2, and tumor necrosis factor [TNF]-). 
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
Cellular responses to filovirus GPs and/or TAFV NP, if assays are available. 

Phenotypic and functional analysis of B, T and/or natural killer (NK) cells and other 
immune cell populations.
Immunogenicity Assessments 
9.3.2.
Details on sample collection and handling are provided in Section 9.5. In case of insufficient 
blood sample volume to perform assays, the samples will be analyzed according to the following 
priority ranking (ranked in order of decreasing priority): 1) core secondary endpoints, 2) core 
exploratory endpoints and 3) additional exploratory endpoints. 
Core Immunogenicity Assessments in Cohorts II and III
Table 4 provides an overview of the core immunogenicity assessments (humoral and cellular 
assays) in Cohorts II and III. Blood samples for core immunogenicity assessments for the 
evaluation of secondary and exploratory endpoints as planned by the sponsor will be collected at 
the time points indicated in the Time and Events Schedule. 
Blood samples (10 mL) for assessment of humoral immune responses will be obtained from all 
subjects in Cohorts II and III. Blood samples (40 mL) for assessment of cellular immune 
responses will be obtained from subjects in Cohorts II and III at selected sites with the 
capabilities to process PBMC (targeted at 10% of all subjects).
Table 4:
Overview of Core Immunogenicity Assessments in Cohorts II and III
Sample
Core Immunogenicity Assessments (non-exhaustive)
Assays (non-exhaustive)
Serum, all 
subjects from 
Cohorts II and 
III
Analysis of antibodies binding to EBOV GPs
Analysis of neutralizing antibodies to EBOV GPs
Analysis of binding and/or neutralizing antibodies to 
adenovirus and/or MVA 
Analysis of EBOV GP, Filovirus GPs and/or TAFV NP 
antibody characteristics, including IgG subtyping 
ELISA
Virus neutralization assay
Adenovirus and/or MVA ELISA and/or
neutralization assay
Molecular antibody characterization 
PBMC, subjects 
from Cohorts II 
and III at selected 
sitesa
T-cell IFN-γ responses to EBOV GP 
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)
ELISpot
ICS
ELISA: enzyme-linked immunosorbent assay; ELISpot: enzyme-linked immunospot; ICS: intracellular cytokine 
staining; IFN: interferon; IgG: immunoglobulin G; IL: interleukin; TNF: tumor necrosis factor
a With the capabilities to process PBMC (targeted at 10% of all subjects).
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Specific Immunogenicity Assessments in Cohort I and Additional Immunogenicity 
Assessments in Cohort II 
Table 5 provides an overview of the specific immunogenicity assessments in Cohort I. Blood 
samples for plasmablast response kinetics will be collected in Cohort I at the time points 
indicated in the Additional Time and Events Schedule for the determination of the optimal 
sampling time points of the B-cell response as part of the additional immunogenicity assessments 
in Cohort II in the UK.
Table 5:
Overview of Specific Immunogenicity Assessments by Academic Consortium Partners in 
Cohort I
Academic Consortium 
Partner/Laboratory
Specific Immunogenicity 
Assessments
Max. Blood Volume 
per Sampling Point
No. of Subjects 
Targeted per Group 
University of Oxford
Kinetics of B-cell response 
(B-cell ELISpot)
10 mL, PBMC
10
Transcriptomicsa
3 mL, TempusTM tube
Alla
a Optional blood samples (for transcriptomics) only to be obtained from subjects who consent separately. 
Table 6 provides an overview of the additional immunogenicity assessments in Cohort II. Blood 
samples for additional immunogenicity assessments for the evaluation of additional exploratory 
endpoints as planned by the academic consortium partners will be collected from subjects in
Cohort II at the time points indicated in the Additional Time and Events Schedule. Blood 
samples will be collected for DNA isolation (in the UK), transcriptomics (in both countries), and 
EBOV neutralization (in France) from all subjects in Cohort II. For the other assays listed in 
Table 6, blood samples will be collected from all subjects in Cohort II in the UK, but initially
only 25 subjects per group will be targeted for analysis, while in France, blood samples will be 
collected from and analyzed in no more than 25 subjects in Groups 1 and 2 in Cohort II at 
selected sites. In addition, these ‘other’ assays have to be performed within the same 25 subjects
per group in the UK and in France. PBMC and serum samples for exploratory immunogenicity 
assessements collected in France may be analyzed in the UK and vice versa.
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Table 6:
Overview of Additional Immunogenicity Assessments by Academic Consortium Partners in 
Cohort II
Academic Consortium 
Partner/Laboratorya
Potential Additional 
Immunogenicity Assessments
Max. Blood Volume 
per Sampling Point
No. of Subjects 
Targeted per Group 
University of Oxford
DNA isolationb
2 mL, whole blood 
Allb
Transcriptomicsc
3 mL, TempusTM tube
Allc
Repertoire sequencing
Isolation of monoclonal Ab
Plasmablast phenotyping
25 mL (10 mL pre-
prime), PBMC
25d
Memory B-cell characterization
25 mL, PBMC
Fresh ICS 
10 mL, whole 
blood/PBMC
INSERM
EBOV neutralization
3 mL, serum 
All
Transcriptomicsc
3 mL, TempusTM tube
Allc
Fresh ICS 
10 mL, whole 
blood/PBMC
25e,f
T cell proliferation
10 mL, PBMC 
T cell phenotyping (including TfH)
4 mL, PBMC 
Cytokine profiling
3 mL, serum 
London School of Hygiene 
and Tropical Medicinef
NK cell analysisf
4 mL, PBMC and
2 mL, serumf
Ab: antibody; No.: number; TfH: T follicular helper
a PBMC and serum samples for exploratory immunogenicity assessments collected in France may be analyzed in 
the UK and vice versa.
b Optional blood sample (for DNA) only to be obtained from subjects who consent separately. 
c Optional blood samples (for transcriptomics) only to be obtained from subjects who consent separately. 
d Blood samples to be collected from all subjects in Cohort II in the UK, but initially only 25 subjects per group will 
be targeted for analysis.
e Blood samples to be collected from and analyzed in no more than 25 subjects in Groups 1 and 2 in Cohort II at 
selected sites in France.
f Blood sampling for NK cell analysis done in France, but analysis performed at London School of Hygiene and 
Tropical Medicine.
Buffy coats will be obtained from the National Blood Transfusion Service (UK) for use of the 
PBMC in the validation and control of the B-cell ELISpot and memory B-cell characterization.
9.4.
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 Section 4.2). 
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 
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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).
9.5.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the CRF or laboratory 
requisition form. Refer to the Time and Events Schedule and the Additional Time and Events 
Schedule for the timing and frequency of all sample collections.
Sample collection and processing will be performed by the study-site personnel according to 
current versions of approved standard operating procedures.
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 
VACCINATION/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 visit (or Day 365 if no boost vaccination was 
administered) for subjects who received placebo or at the Day 365 visit for subjects who 
received active vaccine. A subject who agrees to participate in the roll-over study will be 
considered to have completed the study when he or she completed the last safety-related visit in 
the current study (VAC52150EBL2001) or when he or she has been followed for an additional 
12 months (whichever comes first).
10.2.
Discontinuation of Study Vaccination/Withdrawal From the Study
Discontinuation of Study Vaccination
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. 
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 will be permanently discontinued in case any of the following listed 
criteria is met:

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;
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
The subject experiences any of the events 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. 
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 IEC/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 per the assessments for the 21-day 
post-boost visit. 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 vaccine regimen as the withdrawn subject. No additional subjects will be 
enrolled in case subjects withdraw from the study after receiving the prime vaccination. 
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10.3.
Withdrawal From the Use of Research Samples
A subject who withdraws from the study will have the following options regarding the optional 
research samples or for storage of samples for future use:

The collected samples will be retained and used in accordance with the subject's original 
informed consent for optional research samples or for storage of samples for future use.

The subject may withdraw consent for optional research samples or for storage of samples 
for future use, 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 optional research samples and to 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.
Withdrawal From the Optional Research Samples While Remaining in the Main Study
The subject may withdraw consent for optional research samples while remaining in the study. In 
such a case, the optional research samples will be destroyed. The sample destruction process will 
proceed as described above.
Withdrawal From Storage of Samples for Future Use While Remaining in the Study
The subject may withdraw consent for storage of samples for future use (refer to Section 16.2.5) 
while remaining in the study. In such a case, the samples will be destroyed as described above. 
Details of the sample retention for research are presented in the ICF.
11.
STATISTICAL METHODS
Statistical analysis on subject information, safety and core immunogenicity data will be done by 
the sponsor or under the authority of the sponsor. A general description of the statistical methods 
to be used is outlined below. Specific details will be provided in the Statistical Analysis Plan
(SAP). The analysis to estimate survival based on immunobridging methodology, linking NHP 
immune response data with human immune response data, will be described in a separate SAP.
Separately, data of specific and additional immunogenicity assessments, as outlined in 
Section 9.3.2, will be analyzed by the academic consortium partners. Specific details of these 
analyses will be provided in a separate SAP and reported separately from the Clinical Study 
Report.
Interim analyses may be performed as detailed in Section 11.6. The primary analysis will be 
performed when all subjects have completed the 6-month post-boost visit or discontinued earlier. 
This analysis will include 6-month post-boost safety and all available immunogenicity data up to 
this point. The final analysis will be performed when all subjects have completed the last study-
related visit or discontinued earlier. Note: due to delays in scheduled boost vaccinations caused 
by study pauses, the primary and final analysis may be combined.
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11.1.
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 Immunogenicity 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 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.
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 Immunogenicity analysis 
set, provided more than 10% of subjects in the Immunogenicity analysis set are excluded from 
the Per Protocol analysis set.
11.2.
Sample Size Determination
An originally planned sample size of 612 subjects (pooled across the 3 cohorts) includes 
492 subjects randomized to receive Ad26.ZEBOV and MVA-BN-Filo (in Cohorts II and III) to 
substantially contribute to an overall safety database of the Ad26.ZEBOV and MVA-BN-Filo 
prime-boost regimen. In Cohort I, 30 subjects will receive Ad26.ZEBOV and MVA-BN-Filo in 
an open-label fashion. Randomization to Group 3 was stopped per Amendment 4 to focus on the 
schedules for which an indication will be sought.
As randomization to Group 3 was not resumed, the overall sample size was reduced to 
approximately 543 subjects (Group 1: 204, Group 2: 204, Group 3: 135), with approximately 
469 subjects (Group 1: 174, Group 2: 174, Group 3: 121) to receive Ad26.ZEBOV and MVA-
BN-Filo (in Cohorts II and III) prime-boost regimen. Enrollment in the entire study will be 
stopped per Amendment 5. Details on the impact on the power will be described in the SAP
and/or Clinical Study Report.
The probability of detecting an adverse event in each of the groups, and total, is given in Table 7, 
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 3.3%, 
2.2% and 0.8% for sample sizes of 121, 174 and 499 (ie, total number of subjects in Cohorts I, II, 
and III to receive Ad26.ZEBOV and/or MVA-BN-Filo) subjects, respectively.
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Table 7:
Probability of Observing at Least One Adverse Event Given a True Adverse Event Incidence
True Adverse Event Incidence (%)
N=30
N=121
N=174
N=469
N=499
0.1
3%
11%
16%
37%
39%
0.5
14%
45%
58%
90%
92%
1.0
26%
70%
83%
99%
99%
2.5
53%
95%
99%
100%
100%
5.0
79%
100%
100%
100%
100%
10.0
96%
100%
100%
100%
100%
Having core immunogenicity response data available for 164 subjects per group (ie, 84 from 
Cohort II and 80 from Cohort III), the following pairwise differences in immune response 
(ELISA antibody levels against EBOV GP) between vaccine schedules in Table 8 can be 
detected at any given time point, for a given variability in ELISA antibody levels. With the 
reduction in sample size in Group 3, the power to detect these pairwise differences is at least 
80%.
Table 8:
Magnitude of Pairwise Difference to be Detected Between Vaccine Regimens With Sample Size 
of 164 Subjects
Variability ELISA Antibody Levels (SD, log10 scale)
Detectable Difference (log10 scale) *
0.5
0.20
0.6
0.24
0.7
0.28
0.8
0.32
0.9
0.37
1.0
0.41
1.1
0.45
1.2
0.49
SD: standard deviation; * 90% power, 2-sided test, 5% significance level, accounting for multiple testing
11.3.
Subject Information
For all subjects, demographic characteristics (eg, age, height, weight, body mass index, race, and 
sex) and screening/baseline characteristics (eg, physical examination, medical history) will be 
tabulated and summarized with descriptive statistics.
11.4.
Safety Analyses
No formal statistical testing of safety data is planned. Safety data will be analyzed descriptively 
(including 95% confidence intervals, if applicable), by cohort and overall.
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 
(solicited local, solicited systemic, and unsolicited) will be included in the analysis. For each 
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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 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 on the Full Analysis set. 
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.
Vital Signs and Electrocardiogram 
Vital signs and ECG abnormalities following vaccination will be tabulated by most severe
abnormality grade.
Physical Examination
Physical examination abnormalities following vaccination will be tabulated by most severe
abnormality grade.
11.5.
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. 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. In addition, differences between the vaccination schedules will be 
evaluated at the 21-day post-boost, 6-month post-boost and Day 365 visits.
Integrative statistical analysis of the gene expression and functional assays and modeling 
analyses of data obtained in Cohort II will be detailed and reported separately from this study.
The SAP will provide details on how the samples from the subjects whose boost is out of 
window due to the pause are to be handled in the statistical analyses.
11.6.
Interim Analyses 
Interim analyses may be performed during the study for regulatory purposes or for the purpose of 
informing future vaccine-related decisions in a timely manner. The results will not influence the 
conduct of the study in terms of early termination or later safety or immunogenicity endpoint 
assessments.
A separate SAP will be prepared before the conduct of an interim analysis.
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11.7.
Independent Data Monitoring Committee 
An IDMC will be established to monitor safety data on an ongoing basis to ensure the continuing 
safety of the subjects enrolled in this study. The 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.
The IDMC will be appointed by the sponsor with recommendations from the Clinical Steering 
Committee (see Section 11.8) 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.
11.8.
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 
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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).
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 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 for 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. 
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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.

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 also 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). 
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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.
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 1. For adverse events not identified in the table, the following guidelines will apply:
Mild
Grade 1
Symptoms causing no or minimal interference with usual 
social and functional activities
Moderate
Grade 2
Symptoms causing greater than minimal interference with 
usual social and functional activities
Severe
Grade 3
Symptoms causing inability to perform usual social and 
functional activities
Note: Only clinically significant abnormalities in laboratory data occurring from signing of the 
ICF onwards will be reported as adverse events and graded using the table above. 
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12.2.
Special Reporting Situations
Safety events of interest on a sponsor study 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.
12.3.
Procedures
Refer to Section 9.1.5 for more information for subjects in France who have further follow-ups 
from Day 365 onwards until the roll-over study is opened.
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 is obtained until the 42-day post-boost visit. 
Serious adverse events and IREs will be collected from signing of the ICF onwards until the end 
of the study. Subjects will record symptoms of solicited local or systemic adverse events 
(reactogenicity) in the diary in the evening after each vaccination and then daily for the next 
7 days. 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. 
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 vaccine. 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. 
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Participating investigators and IEC/IRB will receive a blinded SUSAR summary, unless 
otherwise specified. 
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

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)
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:
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
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 
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.
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Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required.
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 within 3 months 
after vaccination with Ad26.ZEBOV, will be approached to consent for enrollment of their 
offspring into the VAC52150 Vaccine Development Roll-over study, according to the same rules 
that apply for the other subjects (see Section 9.1.6).
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.
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
91
Approved, Date: 20 April 2017
14.
STUDY VACCINE INFORMATION
14.1.
Description of Study Vaccines
Ad26.ZEBOV
Ad26.ZEBOV is a monovalent recombinant, 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.12
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.14
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.
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.
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VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
92
Approved, Date: 20 April 2017
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 study vaccine administrator (see Definitions of Terms). To preserve 
blinding, the unblinded qualified study-site personnel will place a blinding tape on the syringe to 
mask its content.
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.
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
93
Approved, Date: 20 April 2017
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

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.
The total blood volume to be collected is considered to be within the limits of standard blood 
donation. 
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.
Good Clinical Practice is an international ethical and scientific quality standard for designing, 
conducting, recording, and reporting studies that involve the participation of human subjects. 
Compliance with this standard provides public assurance that the rights, safety, and well-being of 
study subjects are protected, consistent with the principles that originated in the Declaration of 
Helsinki, and that the study data are credible.
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
94
Approved, Date: 20 April 2017
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

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.
Approval for the collection of optional samples for research and for the corresponding ICF must 
be obtained from the IEC/IRB. Approval for the protocol can be obtained independent of this 
optional research component.
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)
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VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
95
Approved, Date: 20 April 2017

Reports of adverse events that are serious, unlisted/unexpected, and associated with the 
study vaccine

New information that may adversely affect the safety of the subjects or the conduct of the 
study

Deviations from or changes to the protocol to eliminate immediate hazards to the subjects

Report of deaths of subjects under the investigator's care

Notification if a new investigator is responsible for the study at the site

Development Safety Update Report and Line Listings, where applicable

Any other requirements of the IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct), the amendment and applicable ICF revisions 
must be submitted promptly to the IEC/IRB for review and approval before implementation of 
the change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, 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
16.2.3.
Each subject must give written consent according to local requirements after the nature of the 
study has been fully explained. The ICF(s) must be signed before performance of any study-
related activity. The ICF(s) that is/are used must be approved by both the sponsor and by the 
reviewing IEC/IRB and be in a language that the subject can read and understand. The informed 
consent should be in accordance with principles that originated in the Declaration of Helsinki, 
current ICH and GCP guidelines, applicable regulatory requirements, and sponsor policy.
Before enrollment in the study, the investigator or an authorized member of the study-site 
personnel must explain to potential subjects 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 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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VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
96
Approved, Date: 20 April 2017
The subject will be given sufficient time to read the ICF and the opportunity to ask questions. 
After this explanation and before entry into the study, consent should be appropriately recorded 
by means of the subject's personally dated signature. After having obtained the consent, a copy of 
the ICF must be given to the subject.
Subjects will be asked for consent to provide optional samples for research. After informed 
consent for the study is appropriately obtained, the subject will be asked to sign and personally 
date a separate tick box on the ICF indicating agreement to participate in the optional research 
component. Refusal to participate in the optional research will not result in ineligibility for the 
study. A copy of this signed ICF will be given to the subject.
If the subject 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 is obtained.
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 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 
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.
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
97
Approved, Date: 20 April 2017
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-specified testing is complete, may be stored for up to 15 years 
(or according to local regulations) for possible additional future scientific/genetic research. 
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. Applicable approvals will be sought before any such samples are used for analysis not 
specified in the protocol (amendment) approved by the IEC/IRB.
Stored samples will be coded throughout the sample storage and analysis process and will not be 
labeled with personal identifiers. Subjects may withdraw their consent for their samples to be 
stored for future research at any time (refer to 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.
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.
17.
ADMINISTRATIVE REQUIREMENTS
17.1.
Protocol Amendments
Neither the investigator nor the sponsor will modify this protocol without a formal amendment 
by the sponsor. All protocol amendments must be issued by the sponsor, and signed and dated by 
the investigator. Protocol amendments must not be implemented without prior IEC/IRB 
approval, or when the relevant competent authority has raised any grounds for non-acceptance, 
except when necessary to eliminate immediate hazards to the subjects, in which case the 
amendment must be promptly submitted to the IEC/IRB and relevant competent authority. 
Documentation of amendment approval by the investigator and IEC/IRB must be provided to the 
sponsor. When the change(s) involve(s) only logistic or administrative aspects of the study, the 
IRB/IEC (where required) only needs to be notified.
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
98
Approved, Date: 20 April 2017
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

Signed and dated clinical trial agreement, which includes the financial agreement

Any other documentation required by local regulations
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
99
Approved, Date: 20 April 2017
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 subject diary will be considered a source document. Information from the diary provided to 
subjects to record symptoms of solicited local and systemic adverse events until 7 days after each 
vaccination will be reviewed by the investigator to transcribe into the relevant parts of the CRF 
as described in the CRF Completion Guidelines. 
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
100
Approved, Date: 20 April 2017
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 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, periodic monitoring visits by the sponsor, and direct 
transmission of clinical laboratory data from a central laboratory into the sponsor's database. 
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.
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 
NCT02416453

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
101
Approved, Date: 20 April 2017
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, see Definitions of Terms); 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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VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2001 Amendment 5
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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. 
Similar auditing procedures may also be conducted by agents of any regulatory body, either as 
part of a national GCP compliance program or to review the results of this study in support of a 
regulatory submission. The investigator should immediately notify the sponsor if he/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
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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 
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.
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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.
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).
6.
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).
7.
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.
8.
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.
9.
Friedrich B, Trefry J, Biggins J, et al. Potential vaccines and post-exposure treatments for filovirus 
infections. Viruses. 2012;4(9):1619-1650.
10.
Geisbert TW, Bausch DG, Feldmann H. Prospects for immunisation against Marburg and Ebola viruses. 
Rev Med Virol. 2010;20(6):344-357.
11.
IMVANEX suspension for injection. UK Summary of Product Characteristics. Available at: 
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Product_Information/human/002596/WC500147896.pdf. Accessed 26 March 2015.
12.
Investigator’s Brochure: JNJ-61210474 (Ad26.ZEBOV) Edition 2. Crucell Holland B.V. (20 February 
2015). For updated information, refer to Edition 4 (23 June 2016).
13.
Investigator’s Brochure: JNJ-61210474 (Ad26.ZEBOV) Addendum 1 to Edition 2. Crucell Holland B.V. 
(03 April 2015).
14.
Investigator’s Brochure: MVA-BN-Filo (MVA-mBN226B) Edition 5. Bavarian Nordic A/S (18 March
2015). For updated information, refer to Edition 10 (11 July 2016).
15.
Investigator Brochure: Ad26.ENVA.01 HIV-1 Vaccine. Edition 3. Crucell Holland B.V. (Jun 2013).
16.
Investigator Brochure: JNJ-55471468-AAA, JNJ-55471494-AAA, JNJ-55471520-AAA (Ad26.Mos.HIV) 
HIV 1 vaccine. Edition 2. Crucell Holland B.V. (Nov 2014).
17.
Investigator 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).
18.
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.
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19.
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, Barcelona, Spain.
20.
MVA-BN® (Modified Vaccinia Ankara - Bavarian Nordic). Available at: http://id.bavarian-
nordic.com/pipeline/technology-platform/mva-bn.aspx Accessed 26 March 2015.
21.
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.
22.
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.
23.
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.
24.
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.
25.
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.
26.
WHO Fact Sheet No103 Ebola Virus Disease 2014. Available at: 
http://www.who.int/mediacentre/factsheets/fs103/en/. Accessed 26 March 2015. 
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ATTACHMENTS
Attachment 1: 
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; ms: millisecond; 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; s: second; U: unit; ULN: upper limit of normal
CLINICAL ADVERSE EVENTS
Grading scale used for clinical adverse events is adapted from the 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
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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 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, red blood cell counts or INR. 
Blood, Serum, or Plasma Chemistries a,b
LO/HI/N c
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 d
100-110
111-125
>125
HI e
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
Creatine kinase (CK) (mg/dL) 
N
1.25-1.5xULN
1.6-3.0xULN
≥3.1xULN
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
1.1-2xULN
2.1-3xULN
>3xULN
AST (U/L)
HI
1.1-2.5xULN
2.6-5xULN
>5xULN
ALT (U/L)
HI
1.1-2.5xULN
2.6-5xULN
>5xULN
Bilirubin, serum total (mg/dL)  – when accompanied by any increase 
in Liver Function Test 
1.1-1.25xULN
1.26-1.5xULN
>1.5xULN
Bilirubin, serum total (mg/dL)  – when Liver Function Test is normal
1.1-1.5xULN
1.6-2.0xULN
>2.0xULN
Amylase (U/L)
N
1.1x1.5ULN
1.6-2.0xULN
>2.0xULN
Lipase (U/L)
N
1.1x1.5ULN
1.6-2.0xULN
>2.0xULN
-
                                                
a Depending upon the laboratory used, references ranges, eligibility ranges and grading may be split out by sex and/or age.
b Cardiac troponin I increase by factor: >ULN-<2.0xULN; ≥2.0-<5.0xULN; ≥5.0xULN. (This footnote is added by the sponsor).
c Low, High, Not Graded.
d Fasting.
e Non-fasting.
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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
Prothrombin time (PT, seconds)
HI
1.0-1.10xULN
1.11-1.20xULN
>1.20xULN
International normalized ratio (INR)b
HI
1.1-1.5xULN
1.6-2.0xULN
>2.0xULN
Partial thromboplastin time (PTT or aPTT, seconds)
HI
1.0-1.2xULN
1.21-1.4xULN
>1.4xULN
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 - beats per minute
HI
101-115
116-130
>130 or ventricular 
dysrhythmias
Bradycardia - beats per minute
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 Oral temperature; no recent hot or cold beverages or smoking. 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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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
NCT02416453

 
 
SIGNATURES 
 
 
 
 
Signed by  
Date  
 
Justification  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cynthia Robinson
25Apr2017, 12:58:43 PM, UTC
Document Approval
NCT02416453