A Randomized, Observer-blind, Placebo-controlled, Two-part, Phase 2 Study to Evaluate the Safety, Tolerability and Immunogenicity of Two Prime-boost Regimens of the Candidate Prophylactic Vaccines for Ebola Ad26.ZEBOV and MVA-BN-Filo
Phase: PHASE2
Conditions: Hemorrhagic Fever, Ebola
Sponsor: Janssen Vaccines & Prevention B.V.

1
Status: Approved, Date: 18 September 2017
Janssen Vaccines & Prevention B.V.
Clinical Protocol
A Randomized, Observer-blind, Placebo-controlled, Two-part, Phase 2 Study to Evaluate the 
Safety, Tolerability and Immunogenicity of Two Prime-boost Regimens of the Candidate
Prophylactic Vaccines for Ebola Ad26.ZEBOV and MVA-BN-Filo
Protocol VAC52150EBL2003; Phase 2
AMENDMENT 5
Walter Reed Army Institute of Research and Janssen Vaccines & Prevention B.V.
IND Number: 16280
VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
*Janssen Vaccines & Prevention B.V. (formerly known as Crucell Holland B.V.) is a Janssen 
pharmaceutical company of Johnson & Johnson and is hereafter referred to as the sponsor of the study. 
The sponsor is identified on the Contact Information page that accompanies the protocol.
This study will be conducted under US Food & Drug Administration IND regulations (21 CFR Part 312).
Status:
Approved
Date:
18 September 2017
EDMS number:
EDMS-ERI-108856107, 13.0
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.
NCT02598388

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
2
Status: Approved, Date: 18 September 2017
Protocol History
VAC52150EBL2003_Protocol 
Document Type and
File Name
Issued Date
Comments
Initial Clinical Protocol
VAC52150EBL2003_Protocol
21 September 2015
-
Protocol Amendment 1
VAC52150EBL2003_Protocol_Amend_1
6 November 2015
For details, see Section Amendment_1
Protocol Amendment 2
VAC52150EBL2003_Protocol_Amend_2
8 March 2016
For details, see Section Amendment_2
Protocol Amendment 3
VAC52150EBL2003_Protocol_Amend_3
3 November 2016
For details, see Section Amendment_3
Protocol Amendment 4
VAC52150EBL2003_Protocol_Amend_4
20 April 2017
For details, see Section Amendment_4
Protocol Amendment 5
VAC52150EBL2003_Protocol_Amend_5
This document
For details, see Section Amendment_5

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
3
Status: Approved, Date: 18 September 2017
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 3
LIST OF ATTACHMENTS............................................................................................................................ 6
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 6
PROTOCOL AMENDMENT ......................................................................................................................... 7
SYNOPSIS.................................................................................................................................................. 20
TIME AND EVENTS SCHEDULE .............................................................................................................. 27
ABBREVIATIONS ...................................................................................................................................... 33
DEFINITIONS OF TERMS.......................................................................................................................... 34
1.
INTRODUCTION................................................................................................................................ 35
1.1.
Background .................................................................................................................................... 35
1.2.
Benefit/Risk Section....................................................................................................................... 42
1.2.1.
Known Benefits........................................................................................................................... 42
1.2.2.
Potential Benefits........................................................................................................................ 42
1.2.3.
Known Risks............................................................................................................................... 42
1.2.4.
Potential Risks............................................................................................................................ 42
1.2.5.
Overall Benefit/Risk Assessment ............................................................................................... 43
1.3.
Overall Rationale for the Study...................................................................................................... 45
2.
OBJECTIVES AND HYPOTHESIS ................................................................................................... 46
2.1.
Objectives ...................................................................................................................................... 46
2.2.
Hypothesis ..................................................................................................................................... 48
3.
STUDY DESIGN AND RATIONALE ................................................................................................. 48
3.1.
Overview of Study Design.............................................................................................................. 48
3.2.
Study Design Rationale.................................................................................................................. 53
4.
SUBJECT POPULATION.................................................................................................................. 54
4.1.
Inclusion Criteria ............................................................................................................................ 55
4.1.1.
Inclusion Criteria for Healthy Adult Subjects .............................................................................. 55
4.1.2.
Additional Inclusion Criteria for HIV-infected Subjects............................................................... 57
4.2.
Exclusion Criteria ........................................................................................................................... 58
4.2.1.
Exclusion Criteria for Healthy Adult Subjects ............................................................................. 58
4.2.2.
Additional Exclusion Criteria for HIV-infected Subjects.............................................................. 60
4.3.
Prohibitions and Restrictions ......................................................................................................... 60
5.
TREATMENT ALLOCATION AND BLINDING................................................................................. 60
6.
DOSAGE AND ADMINISTRATION .................................................................................................. 63
6.1.
General Instructions and Procedures ............................................................................................ 63
6.2.
Criteria for Postponement of Vaccination ...................................................................................... 64
6.3.
Contraindications to Boost Vaccination ......................................................................................... 64
7.
TREATMENT COMPLIANCE............................................................................................................ 65
8.
PRESTUDY AND CONCOMITANT THERAPY ................................................................................ 65
9.
STUDY EVALUATIONS .................................................................................................................... 66
9.1.
Study Procedures........................................................................................................................... 66
9.1.1.
Overview..................................................................................................................................... 66

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
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Status: Approved, Date: 18 September 2017
9.1.2.
Screening Phase ........................................................................................................................ 67
9.1.3.
Vaccination Phase...................................................................................................................... 69
9.1.4.
Post-boost Follow-up.................................................................................................................. 70
9.1.5.
VAC52150 Vaccine Development Roll-over Study .................................................................... 71
9.2.
Endpoints ....................................................................................................................................... 71
9.2.1.
Primary Endpoints ...................................................................................................................... 71
9.2.2.
Secondary Endpoint ................................................................................................................... 72
9.2.3.
Exploratory Endpoints................................................................................................................. 72
9.3.
Safety Evaluations ......................................................................................................................... 73
9.3.1.
Safety Assessments ................................................................................................................... 73
9.3.2.
Pausing Rules............................................................................................................................. 77
9.4.
Immunogenicity Evaluations .......................................................................................................... 78
9.5.
Virologic Evaluations...................................................................................................................... 79
9.6.
Pharmacogenomic (DNA) Evaluations .......................................................................................... 79
9.7.
Vaccine-induced Seropositivity...................................................................................................... 80
9.8.
Sample Collection and Handling.................................................................................................... 80
9.9.
Optional Procedures ...................................................................................................................... 80
9.9.1.
Apheresis for Part 1 Subjects ..................................................................................................... 80
9.9.2.
Mucosal Secretions for Part 2 Subjects...................................................................................... 81
10.
SUBJECT COMPLETION/DISCONTINUATION OF STUDY VACCINE/WITHDRAWAL 
FROM THE STUDY ........................................................................................................................... 81
10.1.
Completion ..................................................................................................................................... 81
10.2.
Discontinuation of Study Vaccine/Withdrawal From the Study...................................................... 81
10.3.
Withdrawal From the Use of Research Samples........................................................................... 83
11.
STATISTICAL METHODS................................................................................................................. 83
11.1.
Sample Size Determination ........................................................................................................... 83
11.2.
Analysis Sets.................................................................................................................................. 85
11.3.
Subject Information ........................................................................................................................ 85
11.4.
Safety Analyses ............................................................................................................................. 85
11.5.
Immunogenicity Analyses .............................................................................................................. 86
11.6.
Interim Analyses............................................................................................................................. 87
11.7.
Independent Data Monitoring Committee ...................................................................................... 87
11.8.
Protocol Safety Review Team and Protocol Safety Review Team Reviews ................................. 87
12.
ADVERSE EVENT REPORTING ...................................................................................................... 88
12.1.
Definitions ...................................................................................................................................... 88
12.1.1.
Adverse Event Definitions and Classifications ........................................................................... 88
12.1.2.
Attribution Definitions.................................................................................................................. 90
12.1.3.
Severity Criteria .......................................................................................................................... 91
12.2.
Special Reporting Situations.......................................................................................................... 91
12.3.
Procedures..................................................................................................................................... 91
12.3.1.
All Adverse Events...................................................................................................................... 91
12.3.2.
Serious Adverse Events ............................................................................................................. 93
12.3.3.
Immediate Reportable Events .................................................................................................... 94
12.3.4.
Pregnancy................................................................................................................................... 94
12.4.
Contacting Sponsor Regarding Safety........................................................................................... 95
13.
PRODUCT QUALITY COMPLAINT HANDLING.............................................................................. 95
13.1.
Procedures..................................................................................................................................... 95
13.2.
Contacting Sponsor Regarding Product Quality ............................................................................ 95
14.
STUDY VACCINE INFORMATION ................................................................................................... 96
14.1.
Description of Study Vaccines ....................................................................................................... 96
14.2.
Packaging and Labeling................................................................................................................. 96
14.3.
Preparation, Handling, and Storage............................................................................................... 96
14.4.
Study Vaccine Accountability......................................................................................................... 97

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
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Status: Approved, Date: 18 September 2017
15.
STUDY-SPECIFIC MATERIALS....................................................................................................... 98
16.
ETHICAL ASPECTS ......................................................................................................................... 98
16.1.
Study-specific Design Considerations ........................................................................................... 98
16.2.
Regulatory Ethics Compliance....................................................................................................... 99
16.2.1.
Investigator Responsibilities ....................................................................................................... 99
16.2.2.
Independent Ethics Committee or Institutional Review Board ................................................... 99
16.2.3.
DoD Research Monitor ............................................................................................................. 100
16.2.4.
Informed Consent ..................................................................................................................... 101
16.2.5.
Privacy of Personal Data .......................................................................................................... 102
16.2.6.
Long-term Retention of Samples for Additional Future Research............................................ 102
16.2.7.
Country Selection ..................................................................................................................... 103
17.
ADMINISTRATIVE REQUIREMENTS ............................................................................................ 103
17.1.
Protocol Amendments.................................................................................................................. 103
17.2.
Regulatory Documentation .......................................................................................................... 104
17.2.1.
Regulatory Approval/Notification .............................................................................................. 104
17.2.2.
Required Prestudy Documentation........................................................................................... 104
17.3.
Subject Identification, Enrollment, and Screening Logs .............................................................. 105
17.4.
Source Documentation................................................................................................................. 105
17.5.
Case Report Form Completion .................................................................................................... 105
17.6.
Data Quality Assurance/Quality Control ...................................................................................... 106
17.7.
Record Retention ......................................................................................................................... 106
17.8.
Monitoring .................................................................................................................................... 107
17.9.
Regulatory Audits......................................................................................................................... 107
17.10.
Study Completion/Termination..................................................................................................... 108
17.10.1.
Study Completion/End of Study................................................................................................ 108
17.10.2.
Study Termination..................................................................................................................... 108
17.11.
On-site Audits............................................................................................................................... 108
17.12.
Site-specific addendum................................................................................................................ 108
17.13.
Use of Information and Publication.............................................................................................. 109
REFERENCES.......................................................................................................................................... 111
ATTACHMENTS....................................................................................................................................... 113
INVESTIGATOR AGREEMENT ............................................................................................................... 120
LAST PAGE.............................................................................................................................................. 120

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
6
Status: Approved, Date: 18 September 2017
LIST OF ATTACHMENTS
Attachment 1: 
Test of Understanding (TOU) ...................................................................................... 113
Attachment 2: 
Toxicity Tables for Use in Trials Enrolling Healthy Adults ........................................... 114
Attachment 3:
Hemoglobin Cut-off Values.......................................................................................... 119
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Study Vaccination Schedules Parts 1 and 2............................................................................. 63
Table 2: 
Visit Windows............................................................................................................................ 67
Table 3: 
Summary of Immunologic Assessments in Serum and PBMC................................................. 79
Table 4: 
Probability of Observing at Least One Adverse Event Given a True Adverse Event 
Incidence................................................................................................................................... 84
Table 5: 
Magnitude of Pairwise Difference to be Detected Between Vaccine Regimens for a 
Given Sample Size ................................................................................................................... 84
FIGURES
Figure 1:
Schematic Overview of the Study............................................................................................. 23
Figure 2:
Schematic Overview of the Study............................................................................................. 51

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
7
Status: Approved, Date: 18 September 2017
PROTOCOL AMENDMENT
Amendment_5 (18 September 2017)
The overall reason for the amendment: This amendment was created to increase the number of mucosal sample 
participants in Part 2 of the study, and to remove 2 planned statistical analyses.
The changes made to the clinical protocol VAC52150EBL2003 are listed below, including the rationale of each 
change and a list of all applicable sections.
Rationale: As requested by the Walter Reed Army Institute of Research (WRAIR) the number of mucosal 
sampling participants was increased up to approximately 40% (n= 200) to allow for more robust comparisons 
between study populations.
SYNOPSIS
3.1 Overview of Study Design
Rationale: The note on subjects who have recently received treatment for acute, uncomplicated malaria was 
reworded as the previous wording was confusing.
4.2.1 Exclusion Criteria for Healthy Adult Subjects
Rationale: The protocol states that highly active antiretroviral therapy (HAART) must be recorded in the 
concomitant medication form as a prior medication and any changes to the subject’s HAART regimen must also be 
recorded. This is not how this is currently captured. It needs to be entered on the HIV information page in the 
eCRF and not in the concomitant medications page.
8 PRESTUDY AND CONCOMITANT THERAPY
Rationale: Details on the immunogenicity analyses will be provided in the Statistical Analysis Plan, and were 
removed from the protocol. 
11.5 Immunogenicity Analyses
Rationale: The planned interim analysis when all subjects in Part 1 have completed the 6-month post-boost visit or 
discontinued earlier and the primary analysis when all subjects have completed the 6-month post-boost visit or 
discontinued earlier, have been removed as unblinding has been delayed. In addition, an interim analysis when all 
subjects in Part 1 have completed the 1-year post-boost visit or discontinued earlier has been added.
SYNOPSIS
3.1 Overview of Study Design
5 TREATMENT ALLOCATION AND BLINDING
11 STATISTICAL METHODS
11.4 Safety Analyses
11.5 Immunogenicity Analyses
11.6 Interim Analyses
Rationale: The statistical methods for physical examinations were revised. Only listings will be generated.
SYNOPSIS
11.4 Safety Analyses
Rationale: Minor editorial changes have been made.
Throughout the document

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
8
Status: Approved, Date: 18 September 2017
Amendment_4 (20 April 2017)
The overall reason for the amendment: This amendment is developed in response to changes to the global 
clinical development plan. As of this amendment, the enrollment of subjects from VAC52150EBL2003 to the 
VAC52150EBL4001 Roll-over study is limited to female subjects in Part 2 who became pregnant with estimated 
conception within 28 days after vaccination with MVA-BN-Filo (or placebo) or within 3 months after vaccination 
with Ad26.ZEBOV (or placebo) and children born to those vaccinated female subjects, unless local regulations 
have additional requirements for follow up. After implementation of this amendment, no subjects of Part 1 will be 
approached anymore in this study to roll-over to the VAC52150EBL4001 study. 
See also below for a more extensive rationale regarding this change.
The changes made to the clinical protocol VAC52150EBL2003 are listed below, including the rationale of each 
change and a list of all applicable sections.
Rationale: The original development plan (at the time of the ongoing Ebola epidemic in Africa) was an 
accelerated plan with the anticipation of conducting Phase 3 efficacy studies (with limited safety data collection) 
shortly after Phase 1 and in parallel with Phase 2. The sponsor designed the VAC52150EBL4001 study for the 
extended follow-up of SAEs to enhance the ability for signal detection of rare events. Since there is no longer an 
ongoing Ebola epidemic, it is not currently possible to conduct a parallel Phase 3 efficacy study as part of an 
accelerated development plan. More controlled safety data will have to become available for all vaccinated 
subjects, prior to any potential future efficacy study. In this study, the requirement for entrance to the 
VAC52150EBL4001 Roll-over study will be limited to female subjects in Part 2 who became pregnant with 
estimated conception within 28 days after vaccination with MVA-BN-Filo (or placebo) or within 3 months after 
vaccination with Ad26.ZEBOV (or placebo) and children born to those vaccinated female subjects, unless local 
regulations have additional requirements for follow up. After implementation of this amendment, no subjects of 
Part 1 will be approached anymore in this study to roll-over to the VAC52150EBL4001 study.
SYNOPSIS
3.1 Overview of Study Design
9.1.5 VAC52150 Vaccine Development Roll-over Study
12.3.4 Pregnancy

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
9
Status: Approved, Date: 18 September 2017
Amendment_3 (3 November 2016)
The overall reason for the amendment: The sponsor halted vaccinations in the clinical program following a case 
of Miller Fisher syndrome after receipt of MVA-BN-Filo or placebo in study VAC52150EBL2001 that required 
further assessment to rule out a neurologic and autoimmune event. The current study was paused until the updated 
study-specific informed consent form had been approved to inform the study participants on the additional safety 
information. Based on the request of the Agence Nationale de Sécurité du Médicament et des produits de santé
(ANSM) for study VAC52150EBL2001 in response to the Miller Fisher case, the sponsor has decided to 
implement the collection of neurologic and autoimmune events (“Immediate Reportable Events”) throughout the 
entire clinical development plan.
The changes made to the clinical protocol VAC52150EBL2003 are listed below, including the rationale of each 
change and a list of all applicable sections.
Rationale: As requested by the ANSM, wording on the collection of “Immediate Reportable Events” was added 
after one subject in the study VAC52150EBL2001 experienced a serious and very rare condition called “Miller 
Fisher syndrome” about a month after boost vaccination with either MVA-BN-Filo or placebo. Although the event 
was considered to be unrelated to the vaccine, measures were implemented for the entire clinical development 
plan.
SYNOPSIS
Time and Events Schedule
ABBREVIATIONS
1.1 Background
1.2.5 Overall Benefit/Risk Assessment
3.1 Overview of Study Design
8 PRESTUDY AND CONCOMITANT THERAPY
9.1.2 Screening Phase
9.1.3 Vaccination Phase
9.1.4 Post-boost Follow-up
9.2.1 Primary Endpoints
9.3.1 Safety Assessments
11.4 Safety Analyses
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 consequence of the pause, delays in unblinding are expected. Further details regarding enrollment 
into the VAC52150 roll-over study have been added, such as the inclusion of placebo subjects before unblinding of 
the current study.
SYNOPSIS
3.1 Overview of Study Design
9.1.5 VAC52150 Vaccine Development Roll-over Study
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 event develops.
1.2.5 Overall Benefit/Risk Assessment
9.3.1 Safety Assessments
12.2 Special Reporting Situations
12.3.1 All Adverse Events

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
10
Status: Approved, Date: 18 September 2017
Rationale: The secondary immunogenicity objectives and endpoints were shifted to exploratory objectives and 
endpoints.
SYNOPSIS
2.1 Objectives
9.2.1 Primary Endpoints
9.2.2 Secondary Endpoint
9.2.3 Exploratory Endpoints
9.4 Immunogenicity Evaluations
Rationale: Information regarding rescreening of subjects was added.
SYNOPSIS
Time and Events Schedule
3.1 Overview of Study Design
4.1.2 Additional Inclusion Criteria for HIV-infected Subjects
9.1.2 Screening Phase
Rationale: Information was added to clarify the procedures that need to be followed for subjects who are affected 
by a study pause in the future.
SYNOPSIS
3.1 Overview of Study Design
Rationale: Name change from Crucell Holland B.V. to Janssen Vaccines & Prevention B.V. 
Title Page
1 INTRODUCTION
14.1 Description of Study Vaccines
16.2.3 DoD Research Monitor
REFERENCES
INVESTIGATOR AGREEMENT
Rationale: Safety information following MVA-BN-Filo vaccine administration based on the pooled safety data 
from studies VAC52150EBL1001 and VAC52150EBL1002 has been included.
1.1 Background
1.2.3 Known Risks
1.2.4 Potential Risks
1.3 Overall Rationale for the Study
Rationale: As requested by the Walter Reed Army Institute of Research (WRAIR), a question in the Test of 
Understanding was changed to avoid confusion in the number of visits.
Attachment 1: Test of Understanding (TOU)
Rationale: Clarification was added with regard to which information can be considered as source documentation.
17.4 Source Documentation
Rationale: Information with regard to the stability of highly active antiretroviral therapy was added. 
4.1.2 Additional Inclusion Criteria for HIV-infected Subjects
Rationale: The statistical methods for physical examination, vital signs, and clinical laboratory tests were revised.
For these parameters, only abnormalities will be tabulated by worst abnormality grade.
SYNOPSIS
11.4 Safety Analyses

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
11
Status: Approved, Date: 18 September 2017
Rationale: The protocol has been updated in line with the current protocol template (version 6 June 2016).
4.1.1 Inclusion Criteria for Healthy Adult Subjects
10.2 Discontinuation of Study Vaccine/Withdrawal From the Study
16.2.7 Country Selection
17.1 Protocol Amendments
17.5 Case Report Form Completion
Rationale: Minor textual changes have been made, in addition to modifications for clarity and updates to be in line 
with other current protocols and the current Investigator Brochures.
SYNOPSIS
Time and Events Schedule
ABBREVIATIONS
1.1 Background
1.2.5 Overall Benefit/Risk Assessment
2.1 Objectives
3.1 Overview of Study Design
3.2 Study Design Rationale
5 TREATMENT ALLOCATION AND BLINDING
9.1.4 Post-boost Follow-up
10.1 Completion
10.2 Discontinuation of Study Vaccine/Withdrawal From the Study
11.1 Sample Size Determination
11.2 Analysis Sets
12.1.1 Adverse Event Definitions and Classifications
14.1 Description of Study Vaccines
REFERENCES

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
12
Status: Approved, Date: 18 September 2017
Amendment_2 (8 March 2016)
The overall reason for the amendment: This amendment was created to be in alignment with the 
VAC52150EBL2001 and VAC52150EBL2002 protocols, to remove a planned interim analysis that was 
erroneously added, and to add an additional planned interim analysis. 
The changes made to the clinical protocol VAC52150EBL2003 are listed below, including the rationale of each 
change and a list of all applicable sections. 
Rationale: The planned interim analysis in Part 1 and Part 2 (when all subjects in that part have completed the 
42-day post-boost visit or discontinued earlier), has been removed since the primary analysis will be performed on 
unblinded data at the 6 months post-boost database lock. It has been clarified that the interim analysis in Part 1 
(when all subjects in Part 1 have completed the 21-day post-boost visit or discontinued earlier) will be evaluated 
only from a safety perspective. An additional planned interim analysis will be done when all subjects in Part 1 
have completed the 6-month post-boost visit or discontinued earlier.
SYNOPSIS
3.1 Overview of Study Design
11.5 Immunogenicity Analyses
11.6 Interim Analyses
Rationale: The blood volume for the CD4+ cell count (only for HIV-infected subjects) has been increased to 
4 mL. The blood volume for HIV viral load quantification and sequencing (only for HIV-infected subjects) at 
screening has been increased to 6 mL. Daily and cumulative blood volumes have been updated accordingly. 
Maximum daily and cumulative blood draws have been changed to approximate daily and cumulative blood draws
to allow for retesting in the event of sample hazard.
Time and Events Schedule
9.1.1 Overview
9.3.1 Safety Assessments
9.5 Virologic Evaluations
16.1 Study-specific Design Considerations
Rationale: The statement that a male subject’s study vaccine should be permanently discontinued if his partner 
becomes pregnant, has been removed. The current biodistribution and reprotoxicity data support the 
recommendation that there is a negligible risk to the partner of a male vaccinated subject if she becomes pregnant.
10.2 Discontinuation of Study Vaccine
Rationale: The statement that the birth control method used by the female partner of a male subject should be 
documented, has been removed. The current biodistribution data suggest that there is no vaccine present in tissues 
other than the inoculated muscle and regional lymph nodes. Therefore, the risk to the partner of a male participant 
is negligible and it is unnecessary to confirm additional contraceptive use by the partner. Consistent condom use in 
the male participant will continue to be emphasized.
4.1.1 Inclusion Criteria for Healthy Adult Subjects
4.3 Prohibitions and Restrictions

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
13
Status: Approved, Date: 18 September 2017
Rationale: Immunogenicity objectives, endpoints and assessments have been revised and corrected. The 
secondary objective ‘to assess the kinetics and durability of cellular immune response in healthy and HIV-infected 
adults for EBOV GP insert’ has been moved to the exploratory objectives and the corresponding secondary 
endpoint has been moved to the exploratory endpoints.
SYNOPSIS
2.1 Objectives
9.2.2 Secondary Endpoint
9.2.3 Exploratory Endpoints
9.4 Immunogenicity Evaluations
Rationale: Subjects who received placebo and reach the 1-year post-boost visit (Part 1 and Part 2, Group 2: 
Day 380; Part 2, Group 1: Day 394) prior to unblinding will be required to attend the 1-year post-boost visit.
SYNOPSIS
Time and Events Schedule
3.1 Overview of Study Design
5 TREATMENT ALLOCATION AND BLINDING
9.1.4 Post-boost Follow-up
Rationale: To guarantee a sufficient number of subjects, up to 20 subjects (10 HIV-infected, 10 healthy) from 
Part 1 will be asked to enroll for optional apheresis for collection of peripheral blood mononuclear cell and plasma, 
given that they have provided specific consent for this procedure. Up to a total of 10 Part 1 subjects (irrespective of 
HIV status) with robust immune responses post-boost may also be enrolled for an optional apheresis procedure.
Time and Events Schedule
9.9.1 Apheresis for Part 1 Subjects
Rationale: The description of the doubtful case of pericarditis in the MVA-BN clinical trial program was updated.
1.2.4 Potential Risks
Rationale: Fainting was added as a risk from blood draws.
1.2.4 Potential Risks
Rationale: Inclusion criterion 4 has been modified to specify that subjects with hemoglobin lower than the 
institutional normal reference range should not be included in the study.
4.1.1 Inclusion Criteria for Healthy Adult Subjects
Rationale: The note to inclusion criterion 12 has been modified to clarify that if subjects fail the test of 
understanding (TOU) on the third attempt, they should not continue with the consenting and screening processes.
4.1.1 Inclusion Criteria for Healthy Adult Subjects
Rationale: Inclusion criteria 5 and 7 have been modified to clarify that birth control methods should be used until 
at least 3 months after the boost vaccination.
4.1.1 Inclusion Criteria for Healthy Adult Subjects
Rationale: The 21-day post-boost visit has been added as time point when differences between the vaccination 
schedules will be described.
SYNOPSIS
11.5 Immunogenicity Analyses

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
14
Status: Approved, Date: 18 September 2017
Rationale: The supine position while resting before ECG collection is not required and has therefore been 
removed. The order of safety procedures (vital signs, ECG[s], blood draw) has been removed.
9.3.1 Safety Assessments
Rationale: Further details regarding the VAC52150 Vaccine Development Roll-over study have been added. The 
statement ‘(non-participating) partners of male subjects on active vaccine who become pregnant during the study 
and up to 3 months after the prime vaccination will be approached to consent for enrollment of their children into 
the registry’ has been removed since these children are not part of this roll-over study.
SYNOPSIS
3.1 Overview of Study Design
9.1.5 VAC52150 Vaccine Development Roll-over Study
12.3.4 Pregnancy
Rationale: The name of the participating subject, date, reviewer of the test, and the score has been added to the 
TOU.
Attachment 1: Test of Understanding (TOU)
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
1 INTRODUCTION
2.1 Objectives
3.1 Overview of Study Design
4 SUBJECT POPULATION
5 TREATMENT ALLOCATION AND BLINDING
6.3 Contraindications to Boost Vaccination
9.1.1 Overview
9.1.2 Screening Phase
9.1.3 Vaccination Phase
9.1.4 Post-boost Follow-up
9.3 Safety Evaluations
9.7 Vaccine-induced Seropositivity
9.9.2 Mucosal Secretions for Part 2 Subjects
10.2 Discontinuation of Study Vaccine
10.3 Withdrawal From the Use of Research Samples
12.1.1 Adverse Event Definitions and Classifications
12.3.1 All Adverse Events
12.3.4 Pregnancy
16.1 Study-specific Design Considerations
16.2.4 Informed Consent
16.2.6 Long-term Retention of Samples for Additional Future Research
16.2.7 Country Selection
17.5 Case Report Form Completion
17.6 Data Quality Assurance/Quality Control
17.7 Record Retention

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
15
Status: Approved, Date: 18 September 2017
17.8 Monitoring
REFERENCES
Attachment 2: Toxicity Tables for Use in Trials Enrolling Healthy Adults

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
16
Status: Approved, Date: 18 September 2017
Amendment_1 (6 November 2015)
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. In addition, specific clarifications and 
corrections to the protocol as requested by the Walter Reed Army Institute of Research (WRAIR) Institutional 
Review Board (IRB), Human Subjects Protection Branch (HSPB), and Human Research Protection Office (HRPO)
have been included.
The changes made to the clinical protocol VAC52150EBL2003, dd. 21-Sep-2015, are listed below, including the 
rationale of each change and a list of all applicable sections.
Rationale: As requested by the CBER (US FDA), the 6-month and 1-year visits have been changed to 6-month
post-boost and 1-year post-boost visits.
SYNOPSIS
Time and Events Schedule
1.2.5 Overall Benefit/Risk Assessment
3.1 Overview of Study Design
3.2 Study Design Rationale
4.3 Prohibitions and Restrictions
5 TREATMENT ALLOCATION AND BLINDING
9.1.1 Overview
9.1.4 Post-boost Follow-up
9.3.1 Safety Assessments
10.1 Completion
11 STATISTICAL METHODS
11.5 Immunogenicity Analyses
16.1 Study-specific Design Considerations
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
4.1.1 Inclusion Criteria for Healthy Adult Subjects
9.1.2 Screening Phase
Rationale: The blood sampling volume for cellular assays has been updated due to a switch to Heparin tubes.
Time and Events Schedule
9.1.1 Overview
9.4 Immunogenicity Evaluations
16.1 Study-specific Design Considerations

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
17
Status: Approved, Date: 18 September 2017
Rationale: Footnote "d" related to apheresis for collection of peripheral blood mononuclear cell (PBMC) and 
plasma in a subset of subjects in Part 1 has been added to the blood sampling for cellular assays assessment in the 
Time and Events Schedule. In addition, it has been clarified that the optional apheresis procedure in up to a total of
10 Part 1 subjects (irrespective of human immunodeficiency virus [HIV] status) with robust immune responses 
post-boost will be performed after unblinding at a predefined visits or at an unscheduled visit.
Time and Events Schedule
9.9.1 Apheresis for Part 1 Subjects
Rationale: As requested by the WRAIR HSPB, the description of the vaccination schedule has been reworded.
SYNOPSIS
3.1 Overview of Study Design
Rationale: It has been added that adherence to highly active antiretroviral therapy (HAART) will be assessed at 
every visit in HIV-infected subjects.
Time and Events Schedule
8 PRESTUDY AND CONCOMITANT THERAPY
9.1.3 Vaccination Phase
9.1.4 Post-boost Follow-up
Rationale: The optional consent for mucosal collection in Part 2 has been added to the Time and Events Schedule.
Time and Events Schedule
Rationale: It has been added that stored serum or plasma of HIV-infected subjects may be used to assess 
antiretroviral drug levels.
Time and Events Schedule
9.5 Virologic Evaluations
Rationale: As requested by the WRAIR IRB, text has been added regarding the identification of an estimate of the 
number of subjects that may be screened in the site-specific addendum.
9.1.2 Screening Phase
Rationale: Because urinalysis is only performed at screening, the reference to unexplained hematuria has been 
removed from the pausing rules.
9.3.2 Pausing Rules
Rationale: Details about the collection of oral secretion samples have been added.
9.9.2.2 Collection of Oral Secretion Samples
Rationale: As requested by the WRAIR HSPB, it has been clarified that the interim analysis conducted when all 
subjects in Part 1 have completed the 21-day post-boost visit will be reviewed by the Protocol Safety Review 
Team (PSRT).
SYNOPSIS
3.1 Overview of Study Design
11.6 Interim Analyses

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
18
Status: Approved, Date: 18 September 2017
Rationale: As requested by the WRAIR HSPB, it has been clarified that there will be a single PSRT in which all 
of the Department of Defense (DoD) Research Monitors from each participating site will participate. It has been 
made clear that the list of additional participants in the PSRT is non exhaustive and that the PSRT will also review 
summaries for the Independent Data Monitoring Committee (IDMC) and make clarifications for the IDMC as 
needed.
11.8 Protocol Safety Review Team and Protocol Safety Review Team Reviews
Rationale: As requested by the WRAIR HRPO, the site-specific addendum and site-specific addendum 
amendments have been added to the list of documents that will be provided to the Independent Ethics Committee 
or Institutional Review Board before the start of the study and during the study, respectively.
16.2.2 Independent Ethics Committee or Institutional Review Board
Rationale: As requested by the WRAIR HSPB, the DoD Research Monitor's responsibilities have been revised.
16.2.3 DoD Research Monitor
Rationale: One possible albeit doubtful case of pericarditis observed in the MVA-BN clinical trial program has 
been added to the Potential Risks section.
1.2.4 Potential Risks
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 note on abstinence or natural family planning under inclusion criterion 5 has been revised.
4.1.1 Inclusion Criteria for Healthy Adult Subjects
Rationale: It has been clarified that in study VAC52150EBL1002 no serious adverse events related to vaccination 
have been reported to date.
1.1 Background
Rationale: The protocol has been updated to be in line with the current protocol template (version 14 October 
2015). 
4 SUBJECT POPULATION
9.3.1 Safety Assessments
10 SUBJECT COMPLETION/DISCONTINUATION OF STUDY VACCINE/WITHDRAWAL FROM THE
STUDY
12.2 Special Reporting Situations
12.4 Contacting Sponsor Regarding Safety
13.2 Contacting Sponsor Regarding Product Quality
16.2.2 Independent Ethics Committee or Institutional Review Board
17.1 Protocol Amendments
17.4 Source Documentation
17.5 Case Report Form Completion
17.8 Monitoring
17.10.1 Study Completion/End of Study
17.11 On-site Audits

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
19
Status: Approved, Date: 18 September 2017
17.13 Use of Information and Publication
Rationale: Minor errors have been corrected and minor textual changes have been made.
SYNOPSIS
Time and Events Schedule
1.2.4 Potential Risks
3.1 Overview of Study Design
4.1.2 Additional Inclusion Criteria for HIV-infected Subjects
5 TREATMENT ALLOCATION AND BLINDING
8 PRESTUDY AND CONCOMITANT THERAPY
9.1.1 Overview
9.1.2 Screening Phase
9.9.2.1 Collection of Genital and Rectal Secretion Samples
11.7 Independent Data Monitoring Committee
11.8 Protocol Safety Review Team and Protocol Safety Review Team Reviews
16.2.3 DoD Research Monitor

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
20
Status: Approved, Date: 18 September 2017
SYNOPSIS
A Randomized, Observer-blind, Placebo-controlled, Two-part, Phase 2 Study to Evaluate the Safety, 
Tolerability and Immunogenicity of Two Prime-boost Regimens of the Candidate Prophylactic Vaccines 
for Ebola Ad26.ZEBOV and MVA-BN-Filo.
The sponsor, in collaboration with Bavarian Nordic (BN) and Walter Reed Army Institute of Research
(WRAIR), 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.
Two populations will be studied in this protocol: healthy adults and human immunodeficiency virus 
(HIV)-infected adults, ages 18-70 years inclusive, will be enrolled.
Ad26.ZEBOV and MVA-BN-Filo will be evaluated as a heterologous prime-boost regimen. The first 
schedule to be evaluated is prime vaccination with MVA-BN-Filo followed by a boost with 
Ad26.ZEBOV 14 days later. In the second schedule, Ad26.ZEBOV is used to prime a filovirus-specific 
immune response and MVA-BN-Filo is used to boost the immune response 28 days later. The EBOV GP 
that circulated in West Africa has 97% homology to the EBOV GP used in this vaccine regimen.
STUDY RATIONALE

Enlarge the safety and immunogenicity database for the Ad26.ZEBOV/MVA-BN-Filo 1, 29-day 
prime-boost regimen in healthy adults.

Assess the safety and immunogenicity of Ad26.ZEBOV/MVA-BN-Filo 1, 29-day prime-boost 
regimen in HIV-infected subjects and determine the effect of vaccination on HIV disease.

Enlarge the safety and immunogenicity database for MVA-BN-Filo/Ad26.ZEBOV 1, 15-day 
prime-boost regimen in healthy adults and HIV-infected adults.
OBJECTIVES AND HYPOTHESIS
Primary Objectives

To assess the safety and tolerability of different vaccination schedules of Ad26.ZEBOV and 
MVA-BN-Filo administered intramuscularly (IM) as heterologous prime-boost regimens in healthy 
adults and in HIV-infected adults, with Ad26.ZEBOV prime and MVA-BN-Filo boost vaccination 
on Days 1 and 29, respectively and MVA-BN-Filo prime and Ad26.ZEBOV boost vaccination on 
Days 1 and 15, respectively.

To assess the immune responses to the EBOV GP (as measured by [enzyme-linked immunosorbent 
assay] ELISA antibody concentration) of different vaccination schedules of Ad26.ZEBOV and 
MVA-BN-Filo administered IM as heterologous prime-boost regimens in healthy adults and in 
HIV-infected adults, with Ad26.ZEBOV prime and MVA-BN-Filo boost vaccination on Days 1 and 
29, respectively and MVA-BN-Filo prime and Ad26.ZEBOV boost vaccination on Days 1 and 15, 
respectively.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
21
Status: Approved, Date: 18 September 2017
Secondary Objective
To
compare 
safety 
and 
tolerability 
of 
both 
Ad26.ZEBOV/MVA-BN-Filo 
and 
MVA-BN-Filo/Ad26.ZEBOV regimens between healthy and HIV-infected adults. 
Exploratory Objectives
The exploratory objectives include the following. Some exploratory objectives may not be performed if 
reagents or assays are not available.

To assess the humoral immune responses further regarding kinetics and durability as well as 
neutralizing antibody responses directed against EBOV GP induced by the heterologous prime-boost 
regimen as measured by a virus neutralization assay, at relevant time points of different vaccination 
schedules of Ad26.ZEBOV and MVA-BN-Filo.

To assess the kinetics and durability of cellular immune responses in healthy and HIV-infected 
adults for EBOV GP, by vaccine regimen.

To compare kinetics and durability of humoral and cellular immune responses to EBOV GP of 
Ad26.ZEBOV/MVA-BN-Filo and MVA-BN-Filo/Ad26.ZEBOV regimens between healthy and 
HIV-infected adults.

To assess the kinetics and durability of humoral immune responses, including the development of 
neutralizing antibodies, in healthy and HIV-infected adults for other filovirus GP.

To assess the kinetics and durability of cellular immune responses in healthy and HIV-infected 
adults for other filovirus GP.

To compare kinetics and durability of humoral and cellular immune responses to other filovirus GP, 
of Ad26.ZEBOV/MVA-BN-Filo and MVA-BN-Filo/Ad26.ZEBOV regimens between healthy and 
HIV-infected adults. 

To assess the frequency, magnitude, and durability of anti-vector responses in healthy and 
HIV-infected adults.

To compare kinetics and durability of humoral and cellular immune responses to the EBOV and 
other filovirus GP of Ad26.ZEBOV/MVA-BN-Filo and MVA-BN-Filo/Ad26.ZEBOV regimens 
between adults aged 18-50 and aged 51-70.

To assess the impact of CD4+ count on safety and immunogenicity of Ad26.ZEBOV/MVA-BN-Filo 
and MVA-BN-Filo/Ad26.ZEBOV regimens in HIV-infected adults.

To assess changes in HIV ribonucleic acid (RNA) and HIV specific immune response (using HIV 
antigens in place of Ebola GP) associated with vaccination with Ad26.ZEBOV/MVA-BN-Filo and 
MVA-BN-Filo/Ad26.ZEBOV regimens in HIV-infected adults.

To assess humoral immune responses in genital, rectal and oral secretions in a subset of healthy and 
HIV-infected adults at selected sites for EBOV and other filovirus GP.

To explore the impact of host genetics on immune responses to the Ad26.ZEBOV/MVA-BN-Filo 
and MVA-BN-Filo/Ad26.ZEBOV prime-boost regimens in healthy and HIV-infected adults.

To assess immune epitope breadth elicited by the Ad26.ZEBOV/MVA-BN-Filo and 
MVA-BN-Filo/Ad26.ZEBOV prime-boost regimens in healthy and HIV-infected adults.

To assess the immunoglobulin subclass, glycosylation and effector functions of humoral responses to 
EBOV and other filovirus GP.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
22
Status: Approved, Date: 18 September 2017

To describe B cell, helper T cell, and cytotoxic T cell responses elicited by the 
Ad26.ZEBOV/MVA-BN-Filo and MVA-BN-Filo/Ad26.ZEBOV prime-boost regimens in healthy
and HIV-infected adults.

To explore immune inflammatory responses elicited by the Ad26.ZEBOV/MVA-BN-Filo and 
MVA-BN-Filo/Ad26.ZEBOV regimens in healthy and HIV-infected adults on a multiplex array 
platform to evaluate cytokine and soluble factor responses to vaccination. 
Hypothesis
No formal statistical hypothesis testing is planned for this study. The primary purpose of the study is to 
provide descriptive information regarding safety and immunogenicity of the 2 vaccination regimens 
within cohorts of healthy and HIV-infected subjects.
OVERVIEW OF STUDY DESIGN
This is a randomized, observer-blind, placebo-controlled, parallel-group, multicenter, 2-part, Phase 2 
study to evaluate the safety, tolerability and immunogenicity of different vaccination regimens using 
Ad26.ZEBOV at a dose of 5x1010 viral particles (vp) and MVA-BN-Filo at a dose of 1x108 infectious 
units (Inf U, nominal titer), administered IM. The first regimen to be evaluated is prime vaccination with 
MVA-BN-Filo followed by a boost vaccination with Ad26.ZEBOV 14 days later. The second regimen to 
be evaluated is prime vaccination with Ad26.ZEBOV followed by a boost vaccination with 
MVA-BN-Filo 28 days later. These regimens will be evaluated in healthy and HIV-infected adults. 
A planned total of 575 subjects will be enrolled, with approximately 300 healthy subjects and 
275 HIV-infected subjects. Eligible subjects are those who have never received a candidate Ebola 
vaccine and have no prior exposure to EBOV (including travel to epidemic Ebola areas less than 1 month 
prior to screening) or a diagnosis of Ebola virus disease.
There are 2 parts to this study that will run in parallel. Part 1 features 2 cohorts consisting of 50 healthy 
adults and 25 HIV-infected adults, aged 18-70 years inclusive. Within each cohort, subjects will be 
randomized in a 4:1 ratio to receive Ad26.ZEBOV and MVA-BN-Filo or placebo: MVA-BN-Filo prime 
vaccination followed by Ad26.ZEBOV boost vaccination or placebo prime and boost vaccination 14 days 
later. Randomization will be done separately for healthy subjects and HIV-infected subjects. Part 1 will 
be conducted exclusively in the US at the WRAIR Clinical Research Center.
Part 2 of the study will investigate 2 vaccination regimens: Ad26.ZEBOV prime vaccination followed by 
MVA-BN-Filo boost vaccination 28 days later (Group 1) and MVA-BN-Filo prime vaccination followed 
by Ad26.ZEBOV boost vaccination 14 days later (Group 2). Group 1 includes 2 cohorts consisting of 
200 healthy adults and 200 HIV-infected adults, aged 18-70 years inclusive, randomized in a 4:1 ratio to
receive Ad26.ZEBOV and MVA-BN-Filo or placebo: Ad26.ZEBOV as prime vaccination followed by 
MVA-BN-Filo as boost vaccination or placebo prime and boost vaccination 28 days later. Group 2 
includes 2 cohorts consisting of 50 healthy adults and 50 HIV-infected adults, aged 18-70 years inclusive, 
randomized in a 4:1 ratio to receive Ad26.ZEBOV and MVA-BN-Filo or placebo: MVA-BN-Filo prime 
vaccination followed by Ad26.ZEBOV boost vaccination or placebo prime and boost vaccination 14 days 
later, as shown in Figure 1 and Table 1. Randomization will be done separately for healthy subjects and 
HIV-infected subjects. Randomization of HIV-infected subjects in Part 2 will be contingent upon 
acceptable safety data from HIV-infected subjects from Part 1. An overview of the study design is 
provided below:

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
23
Status: Approved, Date: 18 September 2017
Figure 1:
Schematic Overview of the Study
HIV+: HIV-infected; pbo: placebo;
: time of interim analysis; ▼: time of final analysis 
An Independent Data Monitoring Committee (IDMC) will be commissioned for this study. Refer to 
Section 11.7 for details.
Within each part, study-site personnel (except for those with primary responsibility for study vaccine 
preparation and dispensing), sponsor personnel and subjects will be blinded to the study vaccine 
allocation until all subjects in that part have completed the 6-month post-boost visit or discontinued 
earlier and the database has been locked for that part. For any interim analyses performed in a part before 
database lock, study-site personnel (except for those with primary responsibility for study vaccine 
preparation and dispensing), the sponsor (except for specifically designated sponsor personnel who are 
independent of the study) and subjects will remain blinded to study vaccine allocation.
All subjects will receive the study vaccine (Ad26.ZEBOV, MVA-BN-Filo or placebo) IM in the deltoid 
muscle. In Part 1 and Part 2, Group 2, all subjects will receive MVA-BN-Filo (1x108 Inf U, nominal titer) 
or placebo on Day 1 followed by Ad26.ZEBOV (5x1010 vp) or placebo on Day 15. In Part 2, Group 1, all 
subjects will receive Ad26.ZEBOV (5x1010 vp) or placebo on Day 1, followed by MVA-BN-Filo 
(1x108 Inf U, nominal titer) or placebo on Day 29.
The study consists of a screening phase of up to 8 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 Day 15 or 29, and a post-boost follow-up phase of maximum 
1 year post-boost vaccination. When all subjects in a part have completed the 6-month post-boost visit or 
discontinued earlier, and the database for that part has been locked, the part will be unblinded. At that 
time, 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. The subjects who received Ad26.ZEBOV and 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
24
Status: Approved, Date: 18 September 2017
MVA-BN-Filo will continue the study until the 1-year post-boost vaccination visit to assess long-term 
safety and immunogenicity. However, subjects who received placebo and reach the 1-year post-boost visit 
(Part 1 and Part 2, Group 2: Day 380; Part 2, Group 1: Day 394) prior to unblinding will be required to 
attend the 1-year post-boost visit. 
While Part 1 was enrolling, the sponsor halted all vaccinations in this study due to the occurrence of a 
serious and very rare condition, Miller Fisher syndrome, reported in study VAC52150EBL2001, until a 
thorough medical review was performed to ensure safety of the subjects, a revised ICF was prepared, and 
approval to restart the study was granted by the relevant competent authority. As a result of the delay, 
some subjects in Part 1 may reach the Day 380 visit prior to unblinding of Part 1. Female subjects in 
Part 2 who became pregnant with estimated conception within 28 days after vaccination with 
MVA-BN-Filo (or placebo) or within 3 months after vaccination with Ad26.ZEBOV (or placebo) and 
children born to vaccinated female subjects in Part 2 who became pregnant with estimated conception 
within 28 days after vaccination with MVA-BN-Filo (or placebo) or within 3 months after vaccination 
with Ad26.ZEBOV (or placebo) (unless local regulations have additional requirements for follow up) will 
be eligible for enrollment into the VAC52150EBL4001 Vaccine Development Roll-over study for 
long-term surveillance (for a total of up to 60 months after the prime vaccination). After unblinding, only 
female subjects and the children born to female subjects (with estimated conception within the period 
stated above) in Part 2 who received Ad26.ZEBOV and/or MVA-BN-Filo will be approached to consent
for enrollment in the VAC52150 Vaccine Development Roll-over study for long-term surveillance. After 
unblinding, female subjects and the children born to female subjects (with estimated conception within 
the period stated above) in Part 2 who received placebo and had already been enrolled into the 
VAC52150 Vaccine Development Roll-over study will be discontinued from further participation in the 
roll-over study.
As of amendment 4 implementation, no subjects of Part 1 will be approached anymore in this study to 
roll-over to the VAC52150EBL4001 study.
In the event that the study is paused in the future, subjects who were primed and awaiting boost will be 
followed every 3 months until 1 year for ascertainment of serious adverse events and immediate 
reportable events (IREs). Subjects who received both prime and boost will continue to follow the protocol 
as written. Subjects who are awaiting prime vaccination may need to be rescreened under a new subject 
number, repeating all screening procedures except the test of understanding (TOU) (unless the TOU has 
been revised in the meantime, in which case it needs to be taken again). 
SUBJECT POPULATION
Screening of subjects for eligibility will be performed within 8 weeks before administration of study 
vaccine on Day 1. The study population will consist of a planned total number of 575 subjects, including 
healthy and HIV-infected subjects (aged 18 to 70 years inclusive).
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 and on Day 15 (Part 1 and
Part 2, Group 2) or on Day 29 (Part 2, Group 1) at the following dose levels:

Ad26.ZEBOV: 5x1010 vp, supplied in a single use vial (0.5 mL extractable)

MVA-BN-Filo: 1x108 Inf U (nominal titer; target fill is 1.9x108 Inf U per dose, range: 
1.27-2.67x108 Inf U), supplied in a single use vial (0.5 mL extractable)

Placebo: 0.9% saline (0.5 mL extractable)

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
25
Status: Approved, Date: 18 September 2017
After each vaccination, subjects will remain at the site for a total of 30 (±10) 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
Safety evaluations will be performed as specified in the Time and Events Schedule. 
Safety will be assessed by collection of solicited local and systemic adverse events (reactogenicity), 
unsolicited adverse events, serious adverse events, and IREs. The subjects will be closely observed by 
study-site personnel for 30 (±10) minutes after each 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). 
Any unsolicited, solicited local or systemic adverse events occurring while on site will be documented. 
Upon discharge from the site, subjects will receive a diary, a thermometer and a ruler to measure body 
temperature and solicited local reactions. Subjects will be instructed to record solicited local and systemic 
adverse events in the diary in the evening after each vaccination and then daily for the next 7 days at 
approximately the same time each day. Diaries should be completed at home by the subject. For those 
subjects having difficulty completing the diary independently, the sites will make arrangements to have 
the diary completed according to their local practice. The investigator will document unsolicited adverse 
events from signing of the ICF 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. Other safety 
assessments include physical examination, vital signs (blood pressure, pulse/heart rate, body 
temperature), clinical laboratory and pregnancy testing.
The investigators, together with the sponsor's study responsible physician, 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 or in case of other severe safety concerns.
IMMUNOGENICITY EVALUATIONS
Samples will be collected for immunogenicity assessments as specified in the Time and Events Schedule. 
Serum samples to assess humoral immune response and peripheral blood mononuclear cell (PBMC) 
samples to assess cellular immune response will be taken from all subjects. In Part 2, a subset of 
approximately 40% will also participate in the optional mucosal assessments. Subjects giving informed 
consent for the study will be informed that their leftover blood and secretion samples will be stored for 
potential future research.
PHARMACOGENOMIC EVALUATIONS
The human leukocyte antigen (HLA) type will be determined (where local regulations permit) to explore 
the impact of host genetics on immune responses to the Ad26.ZEBOV/MVA-BN-Filo and 
MVA-BN-Filo/Ad26.ZEBOV prime-boost regimens. No additional venous blood samples need to be 
collected for this evaluation, samples collected on the day of the prime vaccination will be used. Subject 
participation in the pharmacogenomic research is optional and will require additional consent.
STATISTICAL METHODS
An interim analysis will be conducted when all subjects in Part 1 have completed the 21-day post-boost 
visit, or discontinued earlier. The purpose of this interim analysis is to evaluate the effect of vaccination 
on the HIV viral load of HIV-infected subjects from a safety perspective. This interim analysis will be 
reviewed by the Protocol Safety Review Team (PSRT) and forwarded to the IDMC for review. An 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
26
Status: Approved, Date: 18 September 2017
additional interim analysis will be done when all subjects in Part 1 have completed the 1-year post-boost 
visit or discontinued earlier. Additional (ad hoc) interim analyses may be performed during the study 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 unless a significant safety concern has been identified.
For any interim analyses performed in a part before database lock, study-site personnel (except for those 
with primary responsibility for study vaccine preparation and dispensing), the sponsor (except for 
specifically designated sponsor personnel who are independent of the study) and subjects will remain 
blinded to study vaccine allocation.
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 Statistical Analysis Plan (SAP).
Safety Analyses
Safety data will be analyzed descriptively (including 95% confidence intervals, if applicable). For each 
adverse event, the number and percentage of subjects who experience at least 1 occurrence of the given 
event will be summarized by group. Summaries, listings, datasets, or subject narratives may be provided, 
as appropriate, for those subjects who die, who discontinue study vaccine due to an adverse event, or who 
experience a severe or a serious adverse event. Abnormalities in vital signs and clinical laboratory tests
will be tabulated by worst abnormality grade. Physical examination abnormalities will be listed. 
Exploratory statistical testing of safety data may be performed.
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. 
Response patterns over time for the immunologic parameters will be analyzed, taking into account 
within-subject correlations, to describe differences between the vaccination schedules at 21 days 
post-boost, 42 days post-boost, 6 months post-boost and 1 year post-boost. Exploratory statistical testing 
of immunogenicity data may be performed.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
27
Status: Approved, Date: 18 September 2017
TIME AND EVENTS SCHEDULE
Part 1
Screening 
Phasea
(≤ 8 weeks)
Vaccination Phase and Post-boost Follow-upb,c
D1
D2-D7
D8
D15
D16-D21
D22
D36
D57
D195
D380
Study Procedures
Screening/Administrative
Informed consent
X
Consent for apheresis (optional)d
X
Inclusion/exclusion criteria
X
Medical history and 
demographics
X
Prestudy therapiese
X
Test of Understanding (TOU)f
X
Review Screening Datag
X
Randomization
X
Study Vaccine Administrationh,i
▼
▲
Antiretroviral therapy adherence 
check, if applicableu
X
X
X
X
X
X
X
X
X
Safety Assessments
Electrocardiogram
Xj
Urine pregnancy testk,l
X
X
X
Physical examinationm
X
X
X
X
X
X
X
X
X
Vital signsn
X
X
X
X
X
X
X
X
X
Distribution of subject diaryo
X
X
Completion of diary at homep
X
X
X
X
Review of diary by site staff
X
X
Adverse eventsq
Continuous
Serious adverse events and 
immediate reportable eventsr
Continuous
Concomitant medications
X
X
X
X
X
X
X
X
Xs
Xs
Xs
Clinical Lab Assessments
Chemistry (ALT, creatinine)
(4 mL)
X
X
X
X
X
Hematologyt (3 mL)
X
X
X
X
X
Urinalysis
X

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
28
Status: Approved, Date: 18 September 2017
Screening 
Phasea
(≤ 8 weeks)
Vaccination Phase and Post-boost Follow-upb,c
D1
D2-D7
D8
D15
D16-D21
D22
D36
D57
D195
D380
HIV-1 or HIV-1/2 serology
(6 mL)
X
CD4+ cell countu (4 mL)
X
X
X
X
X
X
X
Immunogenicity and Virologic 
Assessmentsv
Blood sampling for humoral 
assays (16 mL)
Xw
Xw
X
X
X
X
Blood sampling for cellular 
assays (80 mL)d
Xw
Xw
X
X
X
X
HIV viral load quantification and 
sequencingu,x (6 mL at screening, 
4 mL at other visits)
X
X
X
X
X
X
X
Approximate daily blood drawsy
(mL)
23
111
0
7
111
0
7
104
104
104
104
Approximate cumulative blood 
drawsy (mL)
23
134
134
141
252
252
259
363
467
571
675
▲ Ad26.ZEBOV 5x1010 vp or placebo ▼ MVA-BN-Filo 1x108 Inf U or placebo
NOTE: In case of early withdrawal from the study, early withdrawal assessments (ie, physical examination, vital signs, CD4+ cell count [as applicable], [serious] 
adverse events and concomitant medications review, immunogenicity, and virologic assessments) should be obtained. Subjects who wish to withdraw consent will be 
offered an optional visit for safety follow-up (before the formal withdrawal of consent); the subject has the right to refuse.
a.
Screening may be split into multiple days or visits. Retesting of values (eg, safety laboratory) that lead to exclusion is allowed only once using an 
unscheduled visit during the screening phase. The safety laboratory assessments at screening are to be performed within 28 days prior to the prime 
vaccination and may be repeated if they fall outside this time window. If rescreening is required, all screening procedures (except TOU) should be repeated
(unless the TOU has been revised in the meantime, in which case it needs to be taken again) (see Section 9.1.2). 
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 a part (ie, when the last subject in that part completed the 6-month post-boost visit or discontinued earlier), 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 1-year post-boost visit (Part 1 and Part 2, Group 2: Day 380; Part 2, Group 1: Day 394) prior to unblinding will be required to attend the 
1-year post-boost visit.
c.
Only subjects who received Ad26.ZEBOV or MVA-BN-Filo will be followed up for collection of serious adverse event and immediate reportable event 
information post unblinding.
d.
Up to 20 subjects (10 HIV-infected, 10 healthy) from Part 1 will be asked to enroll for optional apheresis for collection of peripheral blood mononuclear 
cell (PBMC) and plasma on the Day 36 and Day 57 visit, given that they have provided specific consent for this procedure. Up to a total of 10 Part 1 
subjects (irrespective of HIV status) with robust immune responses post-boost may also be enrolled for an optional apheresis procedure performed after 
unblinding at a predefined visits or at an unscheduled visit for better characterization of immune responses.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
29
Status: Approved, Date: 18 September 2017
e.
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). 
f.
After reading but before signing the informed consent form (ICF), the TOU will be conducted (or as required per local regulations and practice). The ICF 
needs to be signed before any other study-related activities occur.
g.
The investigators should ensure that all study enrollment criteria have been met at the end of the screening phase. Minimum criteria for the availability of 
documentation supporting the eligibility criteria are described in Section 17.4.
h.
After each vaccination, subjects will remain at the site for a total of 30 (±10) 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.
i.
Phlebotomy, indicated pregnancy tests, physical examination and measurements of vital signs will occur prior to study vaccine administration.
j.
Only for subjects >50 years. A single, 12-lead electrocardiogram (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.
k.
Only for women of childbearing potential. A urine pregnancy test should be performed prior to each vaccination administration.
l.
Pregnancies will be reported from signing of the ICF until the end of the study.
m.
A full physical examination, including height and body weight, will be carried out at screening. A genitourinary examination is not required. At other 
visits, an abbreviated, symptom-directed examination will be performed as indicated by the investigator. 
n.
Includes blood pressure, pulse/heart rate (at rest) and body temperature (oral or axillary). The site of body temperature measurement must be captured in 
the CRF.
o.
Diary cards will be used as memory aids to document solicited adverse events by the subject.
p.
Subjects will use the subject diary to document solicited local and systemic adverse events (reactogenicity) in the evening after each vaccination and then 
daily for the next 7 days at approximately the same time each day. Diaries should be completed at home by the subject. For subjects having difficulty 
completing the diary independently, the sites will make arrangements to have the diary completed according to their local practice.
q.
Solicitation of any cardiac sign or symptom must be performed at every visit and if indicated, an ECG and/or troponin I levels and/or echocardiogram 
should be obtained.
r.
For reporting of immediate reportable events, refer to Section 12.3.3.
s.
After the 42-day post-boost visit, concomitant therapies should only be recorded if given in conjunction with serious adverse events and immediate 
reportable events.
t.
Complete blood count with differential.
u.
Only for HIV-infected subjects.
v.
Stored serum or plasma of HIV-infected subjects may be used to assess antiretroviral drug levels.
w.
Prior to study vaccine administration.
x.
Viral sequencing may be performed if the HIV viral load is sufficiently high.
y.
Additional blood may be drawn to confirm and follow-up on adverse events.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
30
Status: Approved, Date: 18 September 2017
Part 2, Groups 1 and 2
Screening 
Phasea
(≤8 weeks)
Vaccination Phase and Post-boost Follow-upb,c
Group 1 n=400
D1
D2-D7
D8
D29
D30-
D35
D36
D50
D71
D209
D394
Group 2 n=100
D15
D16-
D21
D22
D36
D57
D195
D380
Study Procedures
Screening/Administrative
Informed consent
X
Consent for mucosal secretions 
collections (optional)
X
Inclusion/exclusion criteria
X
Medical history and demographics
X
Prestudy therapiesd
X
Test of Understanding (TOU)e
X
Review Screening Dataf
X
Randomization
X
Study Vaccine Administrationg,h
▲
▼
▼
▲
Antiretroviral therapy adherence 
check, if applicablet
X
X
X
X
X
X
X
X
X
Safety Assessments
Electrocardiogram
Xi
Urine pregnancy testj,k
X
X
X
Physical examinationl
X
X
X
X
X
X
X
X
X
Vital signsm
X
X
X
X
X
X
X
X
X
Distribution of subject diaryn
X
X
Completion of subject diary at 
homeo
X
X
X
X
Review of diary by site staff
X
X
Adverse eventsp
Continuous
Serious adverse events and 
immediate reportable eventsq
Continuous
Concomitant medications
X
X
X
X
X
X
X
X
Xr
Xr
Xr
Clinical Lab assessments
Chemistry (ALT, Creatinine)
(4 mL)
X
X
X
X
X
Hematologys (3 mL)
X
X
X
X
X

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
31
Status: Approved, Date: 18 September 2017
Screening 
Phasea
(≤8 weeks)
Vaccination Phase and Post-boost Follow-upb,c
Group 1 n=400
D1
D2-D7
D8
D29
D30-
D35
D36
D50
D71
D209
D394
Group 2 n=100
D15
D16-
D21
D22
D36
D57
D195
D380
Urinalysis
X
HIV-1 or HIV-1/2 serology
(6 mL)
X
CD4+ cell countt (4 mL)u
X
X
X
X
X
X
X
Immunogenicity and Virologic 
Assessmentsv
Mucosal secretions collections 
(optional)w
Xx
Xx
X
X
X
X
Blood sampling for humoral 
assays (16 mL)
Xx
Xx
X
X
X
X
Blood sampling for cellular assays 
(80 mL)
Xx
Xx
X
X
X
X
HIV viral load quantification and 
sequencingt,y (6 mL at screening, 4 
mL at other visits)
X
X
X
X
X
X
X
Approximate daily blood 
drawsz(mL)
23
111
0
7
111
0
7
104
104
104
104
Approximate cumulative blood 
drawsz (mL)
23
134
134
141
252
252
259
363
467
571
675
▲ Ad26.ZEBOV 5x1010 vp or placebo ▼ MVA-BN-Filo 1x108 Inf U or placebo
NOTE: In case of early withdrawal from the study, early withdrawal assessments (ie, physical examination, vital signs, CD4+ cell count [as applicable], [serious] 
adverse events and concomitant medications review, immunogenicity, and virologic assessments) should be obtained. Subjects who wish to withdraw consent will be 
offered an optional visit for safety follow-up (before the formal withdrawal of consent); the subject has the right to refuse.
a.
Screening may be split into multiple days or visits. Retesting of values (eg, safety laboratory) that lead to exclusion is allowed only once using an 
unscheduled visit during the screening phase. The safety laboratory assessments at screening are to be performed within 28 days prior to the prime 
vaccination and may be repeated if they fall outside this time window. If rescreening is required, all screening procedures (except TOU) should be repeated
(unless the TOU has been revised in the meantime, in which case it needs to be taken again) (see Section 9.1.2).
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 in a part (ie, when the last subject in that part completed the 6-month post-boost visit or discontinued earlier), 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 1-year post-boost visit (Part 1 and Part 2, Group 2: Day 380; Part 2, Group 1: Day 394) prior to unblinding will be required to attend 
the 1-year post-boost visit.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
32
Status: Approved, Date: 18 September 2017
c.
Only subjects who received Ad26.ZEBOV or MVA-BN-Filowill be followed up for collection of serious adverse event and immediate reportable event
information post unblinding.
d.
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 CRF. 
e.
After reading but before signing the ICF, the TOU will be conducted (or as required per local regulations and practice). The ICF needs to be signed before 
any other study-related activities occur.
f.
The investigators should ensure that all study enrollment criteria have been met at the end of the screening phase. Minimum criteria for the availability of 
documentation supporting the eligibility criteria are described in Section 17.4.
g.
After each vaccination, subjects will remain at the site for a total of 30 (±10) 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.
h.
Phlebotomy, indicated pregnancy test, physical examination and measurements of vital signs will occur prior to study vaccine administration.
i.
Only for subjects >50 years. 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.
j.
Only for women of childbearing potential. A urine pregnancy test should be performed prior to each vaccination administration.
k.
Pregnancies will be reported from signing of the ICF until the end of the study.
l.
A full physical examination, including height and body weight, will be carried out at screening. A genitourinary examination is not required. At other 
visits, an abbreviated, symptom-directed examination will be performed as indicated by the investigator.
m.
Includes blood pressure, pulse/heart rate (at rest) and body temperature (oral or axillary). The site of body temperature measurement must be captured in 
the CRF.
n.
Diary cards will be used as memory aids to document solicited adverse events by the subject.
o.
Subjects will use the subject diary to document solicited local and systemic adverse events (reactogenicity) in the evening after each vaccination and then 
daily for the next 7 days at approximately the same time each day. Diaries should be completed at home by the subject. For subjects having difficulty 
completing the diary independently, the sites will make arrangements to have the diary completed according to their local practice.
p.
Solicitation of any cardiac sign or symptom must be performed at every visit and if indicated, an ECG and/or troponin I levels and/or echocardiogram 
should be obtained.
q.
For reporting of immediate reportable events, refer to Section 12.3.3.
r.
After the 42-day post-boost visit, concomitant therapies should only be recorded if given in conjunction with serious adverse events and immediate 
reportable events.
s.
Complete blood count with differential.
t.
Only for HIV-infected subjects.
u.
The site’s Standard Operating Procedure will be followed with regard to the blood volumes for CD4+ cell count.
v.
Stored serum or plasma of HIV-infected subjects may be used to assess antiretroviral drug levels.
w.
Includes collection of genital, rectal and oral secretions.
x.
Prior to study vaccine administration.
y.
Viral sequencing may be performed if the HIV viral load is sufficiently high.
z.
Additional blood may be drawn to confirm and follow-up on adverse events.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
33
Status: Approved, Date: 18 September 2017
ABBREVIATIONS
Adxx
adenovirus serotype xx (vector)
Ad26.ZEBOV
adenovirus serotype 26 expressing the Ebola virus Mayinga glycoprotein
AIDS
acquired immunodeficiency syndrome
ART
antiretroviral therapy
β-hCG
β-human chorionic gonadotropin
BMI
body mass index
BN
Bavarian Nordic
CBER
Center for Biologics Evaluation and Research
(e)CRF
(electronic) case report form 
DMID
Division of Microbiology and Infectious Diseases
DNA
deoxyribonucleic acid
DoD
Department of Defense
EBOV
Ebola virus
eDC
electronic data capture
ECG
electrocardiogram
EDTA
ethylenediaminetetraacetic acid
ELISA
enzyme-linked immunosorbent assay
ELISpot
enzyme-linked immunospot
EU
European Union
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GMP
Good Manufacturing Practice
GP
glycoprotein
HAART
highly active antiretroviral therapy
HIV
human immunodeficiency virus
HRPO
Human Research Protection Office
HSPB
Human Subjects Protection Branch
ICF
informed consent form
ICH
International Council for Harmonisation
ICS
intracellular cytokine staining
IDMC
Independent Data Monitoring Committee
IEC
Independent Ethics Committee
IFN-γ
interferon-gamma
Ig (X)
immunoglobulin (X)
IL
interleukin
IM
intramuscular(ly)
Inf U
infectious units
IRB
Institutional Review Board
IRE
immediate reportable event
IWRS
interactive web response system
kb
kilobase
MARV
Marburg virus
MedDRA
Medical Dictionary for Regulatory Activities
MVA
Modified Vaccinia Ankara
MVA-BN-Filo
Modified Vaccinia Ankara Bavarian Nordic vector expressing multiple filovirus proteins
NHP
nonhuman primate
NP
nucleoprotein
PBMC
peripheral blood mononuclear cell
PCR
polymerase chain reaction
PI
Principal investigator
PQC
Product Quality Complaint
PSRT
Protocol Safety Review Team
RNA
ribonucleic acid
SAP
Statistical Analysis Plan
SUDV
Sudan virus

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
34
Status: Approved, Date: 18 September 2017
SUSAR
suspected unexpected serious adverse reaction
TAFV
Tai Forest virus
TCID50
50% tissue culture infective dose
THAM
tris (hydroxymethyl)-amino methane
TNF-α
tumor necrosis factor-α
TOU
test of understanding
US
United States
USAMRMC
United States Army Medical Research and Materiel Command
VISP
vaccine-induced seropositivity
VNA
virus neutralization assay
vp
viral particles
WHO
World Health Organization
WRAIR
Walter Reed Army Institute of Research
DEFINITIONS OF TERMS
Study vaccine
Ad26.ZEBOV, MVA-BN-Filo or placebo.
Blinded study vaccine 
administrator
A blinded trained study nurse, medical doctor, or otherwise qualified health care 
provider responsible for administration of study vaccine.
Independent study vaccine 
monitor
An unblinded study vaccine monitor assigned to the study who is responsible for the 
unblinded interface between the sponsor and the investigational site pharmacy.
Solicited adverse events 
(reactogenicity)
Local and systemic adverse events that are common and known to occur after 
vaccination and that are usually collected in a standard, systematic format in vaccine 
clinical studies. For the list of solicited adverse events in this study, see Section 9.3. 
For the purpose of vaccine clinical studies, all other adverse events are considered 
unsolicited; however, this definition should be distinguished from definitions based on 
pharmacovigilance guidelines.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
35
Status: Approved, Date: 18 September 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
Walter Reed Army Institute of Research (WRAIR), 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).11,12 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).22 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 and 
the potential use as a bioweapon.
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

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
36
Status: Approved, Date: 18 September 2017
Nonclinical Studies
Immunogenicity and Efficacy
Immunogenicity and efficacy of the vaccine combination Ad26.ZEBOV and MVA-BN-Filo was 
evaluated in an NHP model (ie, Cynomolgus macaques, Macaca fascicularis). The combination 
was assessed in a multivalent filovirus setting in a small number (2 per regimen) of animals and 
the study included heterologous prime-boost regimens of adenovirus serotype 26 (Ad26), Ad35 
and MVA-BN-Filo vectors expressing different Ebola and Marburg proteins. Full protection 
from Ebola virus disease and death after wild-type EBOV Kikwit 1995 challenge was obtained 
with all heterologous regimens, including the Ad26 and MVA vaccine regimen. All heterologous 
prime-boost regimens induced comparable immune responses against the EBOV Mayinga GP. 
Independently of the vaccine regimen, a strong boost effect was seen after heterologous 
prime-boost immunization. Two additional studies involving more animals are ongoing, to 
strengthen the robustness of the nonclinical efficacy data, and also to optimize the prime-boost 
schedule so as to obtain induction of protective immunity as quickly as possible, to specifically 
respond to the Ebola virus disease outbreak in West Africa.
Toxicology
A repeated-dose toxicity study in rabbits was performed with prime-boost combinations of 
Ad26.ZEBOV and MVA-BN-Filo. The different dose regimens were well tolerated when 
administered twice by intramuscular (IM) injection to New Zealand White rabbits with a 14-day 
interval period. Additionally, the objective was to assess the persistence, reversibility or delayed 
onset of any effects after a 14-day treatment-free period. In the heterologous prime-boost 
regimen, either vector or both were used to prime a filovirus-specific immune response and the 
other/same vector or both were used to boost the immune response 2 weeks later. All vaccine 
dosing regimens resulted in detectable EBOV GP-specific antibody titers. No significant 
toxicological effects (no adverse effects) were observed. The immune response was associated 
with transient increases in fibrinogen, C-reactive protein, globulin, decreases in hematocrit and 
hemoglobin, and microscopic findings in draining iliac lymph nodes, spleen and at the injection 
sites. The findings were noted to be recovering over a 2-week treatment-free period and were 
considered to reflect a physiological response associated with vaccination. There were no effects 
noted that were considered to be adverse.
Biodistribution
Single-dose biodistribution studies in rabbits were performed using the MVA-BN vector or the 
Ad26 vector in combination with another insert (Ad26.ENVA.01: an experimental, prophylactic 
Ad26 vector expressing the human immunodeficiency virus [HIV] type 1, Clade A envelope 
protein). MVA-BN distributed to the skin, muscle, blood, spleen, lung, liver, and pooled lymph 
nodes and was rapidly cleared (within 48 hours following vaccination). Ad26.ENVA.01 was 
primarily localized in the injection site muscle, the regional lymph nodes and the spleen. Three 
months after the single IM injection of Ad26.ENVA.01, the vaccine was cleared from most of 
the examined tissues. As biodistribution is dependent on the vector platform (MVA or Ad26) and 
not on the insert, it can be assumed that recombinant MVA-BN-Filo or Ad26.ZEBOV is 
distributed in the same way as the MVA-BN vector or Ad26.ENVA.01 vector, respectively.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
37
Status: Approved, Date: 18 September 2017
Clinical Studies
To date, no clinical studies have been completed with Ad26.ZEBOV or MVA-BN-Filo. 
However, 4 Phase 1 studies (VAC52150EBL1001, VAC52150EBL1002, VAC52150EBL1003 
and VAC52150EBL1004), 2 Phase 2 studies (VAC52150EBL2001 and VAC52150EBL2002) 
and 1 Phase 3 study (VAC52150EBL3001) are ongoing where monovalent Ad26.ZEBOV 
vaccine and multivalent MVA-BN-Filo vaccine are combined in homologous or heterologous 
prime-boost regimens in which each vector is used to prime a filovirus-specific immune response 
followed by a boost immunization with the same or the other vector 2 to 12 weeks later. Most 
subjects in the 4 Phase 1 studies have been vaccinated and are in follow-up. 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.11,12
Limited data from the ongoing Phase 1 studies with Ad26.ZEBOV and MVA-BN-Filo are 
available. 
VAC52150EBL1001, a first-in-human study, is a randomized, placebo-controlled, observer-
blind study in healthy adults evaluating the safety, tolerability and immunogenicity of 4 regimens 
using MVA-BN-Filo at a dose of 1x108 50% tissue culture infective dose (TCID50) and 
Ad26.ZEBOV at a dose of 5x1010 viral particles (vp): 2 regimens with MVA-BN-Filo as prime 
and Ad26.ZEBOV as boost at a 28- or 56-day interval, and 2 regimens with Ad26.ZEBOV as 
prime and MVA-BN-Filo as boost at a 28- or 56-day interval. A fifth regimen, with 
Ad26.ZEBOV at a dose of 5x1010 vp as prime, and MVA-BN-Filo at a dose of 1x108 TCID50 at a 
14-day interval was evaluated in the open-label, uncontrolled, substudy in healthy adults.
VAC52150EBL1001 has enrolled 87 subjects for which 7-day post-prime safety data, blinded on 
a treatment group level, on 72 subjects (36 per treatment group) are available. Most of the 
adverse events reported were grade 1 or grade 2 in severity. Local injection site reactions were 
reported in 18 (50%) MVA/placebo subjects (all grade 1) and 28 (78%) Ad26/placebo subjects 
(grade 1 [22], grade 2 [5], grade 3 [1]). The most frequent local reaction was injection site pain, 
in 17 (47%) MVA/placebo subjects and 28 (78%) Ad26/placebo subjects, with 1 grade 3 case 
occurring in the Ad26/placebo group. Solicited systemic reactions were reported in 25 (69%) 
MVA/placebo subjects (grade 1 [24] and grade 2 [1]) and 31 (86%) Ad26/placebo subjects 
(grade 1 [22], grade 2 [7], grade 3 [1], unknown [1]). The most frequent systemic reactions were 
fatigue (50% overall), followed by headache (46%) and myalgia (35%). One Ad26/placebo 
subject experienced 3 grade 3 solicited systemic reactions (headache, myalgia and nausea). None 
of the subjects reported fever; however, 2 subjects had 1 temperature measurement missing. The 
most frequent unsolicited adverse events were decreased neutrophils, in 3 (8%) MVA/placebo 
subjects and 6 (17%) Ad26/placebo subjects, followed by activated partial thromboplastin time 
prolongation and hypokalemia, in 3 (8%) MVA/placebo subjects and 5 (14%) Ad26/placebo 
subjects each. Two subjects in the open-label substudy who experienced grade 3 neutropenia did 
not receive the boost vaccination due to contraindications to the boost (as specified in the 
protocol), but continued scheduled assessments as planned. All of these events were transient in 
nature and resolved without intervention. No deaths or serious adverse events related to the 
vaccine were reported during the blinded portion of the study. 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
38
Status: Approved, Date: 18 September 2017
VAC52150EBL1002 is a randomized, placebo-controlled, observer-blind study in healthy adults
evaluating the safety, tolerability and immunogenicity of heterologous and homologous 
prime-boost regimens using MVA-BN-Filo and Ad26.ZEBOV administered in different doses, 
sequences and schedules: MVA-BN-Filo (1x108 TCID50) as prime followed by a Ad26.ZEBOV 
(5x1010 vp) as boost at 14, 28, or 56 days after prime; Ad26.ZEBOV (5x1010 vp) as prime 
followed by MVA-BN-Filo (1x108 TCID50) as boost at 28 days after prime; Ad26.ZEBOV 
(5x1010 vp) as prime followed by a high dose of MVA-BN-Filo (4.4x108 TCID50) as boost at 
14 days after the prime; a high dose of Ad26.ZEBOV (1x1011 vp) as prime followed by a high 
dose of MVA-BN-Filo (4.4x108 TCID50) as boost at 28 days after the prime.
VAC52150EBL1002 completed enrollment of 92 subjects; the blinded phase of the study is 
ongoing. No serious adverse events related to study vaccine have been reported and no safety 
issues have been identified to date.
VAC52150EBL1003 and VAC52150EBL1004 are randomized, placebo-controlled, observer-
blind studies in healthy adults evaluating the safety, tolerability and immunogenicity of 
4 regimens using MVA-BN-Filo at a dose of 1x108 TCID50 and Ad26.ZEBOV at a dose of 
5x1010 vp: 2 regimens had MVA-BN-Filo as prime and Ad26.ZEBOV as boost at a 28- or 
56-day interval, and 2 regimens had Ad26.ZEBOV as prime and MVA-BN-Filo as boost at a 
28- or 56-day interval. The blinded phase of studies VAC52150EBL1003 and 1004 are ongoing 
with enrollment complete in 1003. The blinded safety profile is similar to that reported in 
VAC52150EBL1001 and 1002 studies with so far, fewer reports of solicited local and systemic 
adverse events. No vaccine-related serious adverse events have been reported in either study.
Safety data generated with the 2 vectors containing different inserts are provided below:
Safety Profile of Ad26.ZEBOV
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.13
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 US and Africa.13,14,15

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
39
Status: Approved, Date: 18 September 2017

In the dose-escalation study IPCAVD-001 (n=60), 2 or 3 IM doses of Ad26.ENVA.01 
(1x109, 1x1010, 5x1010, 1x1011 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, 1 of 
them decided to have the 6-month injection. Envelope-specific humoral and cell-mediated 
immune responses were induced at all 4 dose levels of vaccine.2,4

In the single-dose study IPCAVD-003 (n=24), an IM dose of Ad26.ENVA.01 (5x1010 vp) or 
placebo was given to subjects, who were stratified according to baseline Ad26 immune 
status, to evaluate the safety, mucosal immunogenicity and innate immune responses. Local 
reactogenicity comprised moderate injection site pain/tenderness and/or moderate to severe 
erythema which resolved within 3 days of vaccination. Transient systemic reactogenicity 
comprised headache, chills, joint pain, myalgia, malaise/fatigue, and fever. No deaths or 
vaccine-related serious adverse events were observed. Vaccination elicited both systemic 
and mucosal envelope-specific humoral and cellular immune responses. No increased 
activated total or vector-specific mucosal CD4+ T-lymphocytes following vaccination were 
detected in the colorectal mucosa, indicating that vaccination with Ad26 did not increase 
mucosal inflammation.1

In study IPCAVD-004 (n=217), the safety and immunogenicity of IM doses of 
Ad26.ENVA.01 and Ad35.ENV (an Ad35 vector expressing an HIV envelope GP used in 
that study at a dose of 5x1010 vp), given in heterologous and homologous prime-boost 
regimens at 3- versus 6-month intervals, was evaluated. There were 452 adverse events 
reported by 84 of 176 Ad26-vaccine recipients (47.7%), the majority being mild (75.5%) in 
severity. The proportion of subjects with moderate or severe symptoms was not statistically
significantly different between vaccine and placebo. There were 3 serious adverse events: 
2 serious adverse events in placebo recipients (grade 3 peritonsillar abscess and grade 4 
migraine headache, both resolved with no residual effects) and 1 serious adverse event in an 
Ad35/Ad26 vaccine recipient (grade 4 acute myelogenous leukemia, resolved with 
sequelae). No deaths or vaccine-related serious adverse events were reported. Overall, 97%
to
100% of
subjects developed anti-envelope binding antibodies (enzyme-linked 
immunosorbent assay [ELISA]) after a second dose, with heterologous and homologous 
regimens being comparable. Immune responses in groups who received 3- and 6-month 
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.01.16
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 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
40
Status: Approved, Date: 18 September 2017
analysis of adverse events did not show any consistent pattern suggestive of an association of 
Ad35.CS.01 or Ad26.CS.01 with specific adverse events. There were no serious adverse events 
reported during the study. No subject discontinued during a study phase (vaccination or 
challenge) due to adverse events. One subject in the high-dose group completed the vaccination 
phase and the final safety follow-up visit but did not take part in any challenge phase activities 
because of ongoing dyspnea. The most common related adverse events after each vaccination 
were injection site pain, malaise, headache, myalgia and chills. The incidence of vaccine-related 
adverse events was generally higher in the high-dose group than in the low-dose group. In 
general, incidence of malaise, headache, and myalgia were higher after the third dose (Ad26) 
than after the first or second doses (Ad35). Injection site pain was more commonly reported in 
the low and high-dose groups than by placebo subjects. There were no clinically significant 
changes in laboratory test parameters or vital signs data.5
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.
Safety Profile of MVA-BN
MVA-BN is a further attenuated version of the MVA virus, which in itself is a highly attenuated 
strain of the poxvirus Chorioallantois Vaccinia Virus Ankara. MVA-BN induces strong cellular 
activity as well as a humoral (antibody) immune response and has demonstrated an ability to 
stimulate a response even in individuals with pre-existing immunity against Vaccinia. One of the 
advantages of MVA-BN is the virus’ inability to replicate in a vaccinated individual. The 
replication cycle is blocked at a very late stage, which ensures that new viruses are not generated 
and released. This means that the virus cannot spread in the vaccinated person and none of the 
serious side effects normally associated with replicating Vaccinia viruses have been seen with 
MVA-BN.
MVA-BN (MVA-BN®, trade name IMVAMUNE® outside the European Union [EU], invented 
name IMVANEX® in the EU) has received marketing authorization in the EU for active
immunization against smallpox in adults and in Canada for persons 18 years of age and older 
who have a contraindication to the first or second generation smallpox vaccines including 
individuals with immune deficiencies and skin disorders.10 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 subjects (up to age of 80 years), children and subjects in 
whom replicating vaccines are contraindicated (eg, individuals with HIV infection or diagnosed 
with atopic dermatitis), have shown that the platform displays high immunogenicity and a 
favorable safety profile.17 Across all clinical studies, no trends for unexpected or serious adverse 
reactions due to the product were detected.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
41
Status: Approved, Date: 18 September 2017
Safety information was pooled from the first 2 studies of MVA-BN-Filo (VAC52150EBL1001 
and VAC52150EBL1002). In general, MVA-BN-Filo has been shown to be well tolerated.12
Three fifths of the subjects reported at least one local site reaction (injection site pain, 
tenderness, warmth, redness, swelling and/or itching) following administration of MVA-BN-
Filo; mostly of mild severity. The most common reported local site reaction was pain at the 
injection site. All the local reactions resolved to normal without any lasting effects.
At least one general symptom was reported in two fifths of the subjects following MVA-BN-Filo 
administration. The most common general symptoms were fatigue, headache, myalgia (muscle 
pain) and nausea. All general symptoms were transient and resolved without lasting effects.  
Changes in laboratory tests were reported following MVA-BN-Filo administration which 
included hypokalemia and decreased numbers of neutrophils (neutropenia). Both changes in 
laboratory tests were seen in similar numbers of participants following MVA-BN-Filo and the 
dummy (placebo) vaccine. Less frequently, events of decreased hemoglobin levels were 
reported. The changes in laboratory tests were not associated with any complaints or symptoms.
Extensive nonclinical studies support the safety profile of the MVA-BN strain.19,20
Relevant Safety Information from Ongoing VAC52150 Studies
One subject in the study VAC52150EBL2001 experienced a serious and very rare condition 
called “Miller Fisher syndrome”. This condition consists of double vision, pain on moving the 
eye, and difficulty with balance while walking. Miller Fisher syndrome most commonly occurs 
following a recent infection. The subject experienced these symptoms about a week after 
suffering from a common cold and fever. The event happened about a month after boost 
vaccination with either MVA-BN-Filo or placebo. This subject had to go to the hospital for 
treatment and has recovered. After an extensive investigation, the event has been considered to 
be doubtfully related to vaccine and most likely related to the previous common cold.
In the ongoing clinical studies with more than 2,000 participants, there have been a few reports 
of mild to moderate tingling especially in the hands and feet or a sensation of mild to moderate 
muscle weakness in subjects vaccinated with Ad26.ZEBOV or placebo. These symptoms have 
been observed to last no more than 24 to 48 hours in the majority of cases but can last for several 
weeks before going away on their own. These types of symptoms have also been reported 
following administration of other licensed vaccines and following acute viral infections of 
various types. One serious case of probable peripheral sensory neuropathy of moderate severity 
has occurred and has been ongoing for several months, interfering with some of the subject’s
daily activities.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
42
Status: Approved, Date: 18 September 2017
1.2.
Benefit/Risk Section
1.2.1.
Known Benefits
The clinical benefit of prime-boost combinations of Ad26.ZEBOV and MVA-BN-Filo is to be 
established.
1.2.2.
Potential Benefits
Subjects may benefit from clinical testing and physical examination; others may benefit from the 
knowledge that they may aid in the development of an Ebola vaccine. There is no direct 
individual benefit from vaccination for the subjects at the current development stage.
1.2.3.
Known Risks
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.
1.2.4.
Potential Risks
The following potential risks for Ad26.ZEBOV and MVA-BN-Filo will be monitored during the 
study: 
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 9.7.
Risk of Myo/Pericarditis
While replicating smallpox vaccines have been associated with an increased risk to develop 
myo/pericarditis,18 this has not been observed with MVA-BN and is not expected with this 
highly attenuated, non-replicating vaccine. Based on observations with first- and second-
generation replication-competent smallpox vaccines, particular attention has been placed on the 
monitoring for cardiac signs and symptoms in all clinical studies using MVA-BN. Despite the 
close cardiac monitoring, no event indicating a symptomatic case of myo/pericarditis has been 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
43
Status: Approved, Date: 18 September 2017
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 subject (0.3%) met 
the criteria for vaccine-induced myocarditis and eventually the subject was found to suffer from 
exercise-induced palpitations. Self-limited mild elevations in troponin I were recorded in 
3 subjects (0.8%) without evidence of myo/pericarditis.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, nursing baby, or semen is unknown, so female 
subjects of childbearing potential, and male subjects having sexual intercourse with females, 
must agree to practice adequate birth control measures for sexual intercourse from at least 
28 days before the prime vaccination (or prior to prime vaccination for men) until at least 
3 months after the boost vaccination (see Section 4.3). Women who are pregnant or breast-
feeding, or are planning to become pregnant while enrolled in the study until 3 months after the 
boost vaccination, will be excluded from enrollment into the study.
Risks from Blood Draws
Blood draws may cause pain/tenderness, bruising, bleeding, fainting, and, rarely, infection at the 
site where the blood is taken.
Unknown Risks
There are no clinical data on the use of either vaccine (Ad26.ZEBOV or MVA-BN-Filo) in:

Pediatric subjects (<18 years)

Pregnant or nursing women

Adults >50 years

Immunocompromised subjects (including those with HIV infection)
There may be other serious risks that are not known.
1.2.5.
Overall Benefit/Risk Assessment
Based on the available data and proposed safety measures, the overall benefit/risk assessment for 
this clinical study is considered acceptable for the following reasons:

Preliminary safety data from the ongoing Phase 1 studies and safety data generated with the 
2 vaccines with different inserts revealed no significant safety issues (see Sections 1.1 and 
1.2.3). Further experience from Ad26.ZEBOV or MVA-BN-Filo will be gained from 
currently ongoing clinical studies.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
44
Status: Approved, Date: 18 September 2017

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 30 (±10) 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). Refer to 
Section 6.1 for more information on emergency care. Any unsolicited, solicited local or 
systemic adverse events occurring while on site will be documented. Subjects will use a 
diary memory aid to document solicited local and systemic adverse events in the 
evening after each vaccination and then daily for the next 7 days at approximately the 
same time each day. Diaries should be completed at home by the subject. For subjects 
having difficulty completing the diary independently, the sites will make arrangements 
to have the diary completed according to their local practice.

The investigator or the designee will document unsolicited adverse events from signing 
of the informed consent form (ICF) 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 an electrocardiogram (ECG, performed at screening in 
subjects >50 years and at other time points during the study if clinically indicated based 
on signs and symptoms), physical examinations, vital sign measurements, clinical 
laboratory and pregnancy testing, will be performed at scheduled visits during the study, 
which lasts up to 1 year after the boost vaccination in subjects who received 
Ad26.ZEBOV or MVA-BN-Filo. 

Any clinically significant abnormalities (including those persisting at the end of the 
study/early withdrawal) will be followed by the investigator until resolution or until a 
clinically stable endpoint is reached.

Several safety measures are included in this protocol to minimize the potential risk to 
subjects, including the following:

The neuroinflammatory disorders listed in Section 12.1.1 should be categorized as IREs 
and should be reported to the sponsor as described in Section 12.3.3.

There are pre-specified pausing rules that would result in pausing of further vaccination 
if predefined conditions occur, preventing exposure of new subjects to study vaccine 
until an Independent Data Monitoring Committee (IDMC) reviews all safety data (see
Section 9.3.2).

Subjects will discontinue study vaccine for the reasons included in Section 10.2.

If acute illness (excluding minor illnesses such as diarrhea or mild upper respiratory 
tract infection) or fever (body temperature ≥38.0 °C) occur at the scheduled time for 
vaccination, the subject may be vaccinated up to 10 days beyond the window allowed 
for the scheduled vaccination, or be withdrawn from that vaccination at the discretion of 
the investigator and after consultation with the sponsor (see Section 6.2).

Contraindications to boost vaccinations are included in Section 6.3.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
45
Status: Approved, Date: 18 September 2017

If a subject withdraws from the study (withdrawal of consent), he/she maintains the 
option to participate in the safety follow-up (see Section 10.2).
1.3.
Overall Rationale for the Study
In nonclinical studies in the Cynomolgus macaque model, heterologous prime-boost regimens of 
a multivalent mixture of Ad26 vectors (each expressing EBOV Mayinga, SUDV or MARV GP) 
and MVA-BN-Filo provided complete protection against the highly pathogenic wild-type EBOV 
Kikwit 1995 variant (report pending). Further nonclinical studies are ongoing to evaluate the 
protection of the multivalent vaccine regimen in additional animals and to assess the protective 
efficacy of a combination regimen of Ad26.ZEBOV and MVA-BN-Filo (either a simultaneous 
administration or as prime-boost regimen). 
In humans, both Ad26- and MVA-based vaccines containing various antigenic inserts have been 
shown to be safe and immunogenic (see Section 1.1). To date, more than 230 subjects have 
received the sponsor’s Ad26-based vaccines in completed clinical studies (based on the 
adenoviral vaccine safety database report [dated 20 March 2015]). Up to 28 October 2015, 
227 subjects received Ad26.ZEBOV in ongoing studies. The MVA-BN platform is the basis of 
the non-replicating smallpox vaccine registered in Canada and Europe, and has been safely used 
in more than 7,600 humans.17 Although routinely used by the subcutaneous route, MVA-BN at a 
dose of 1x108 TCID50 has been demonstrated to be as safe and immunogenic when used by the 
IM route.8,21 The IM route has been chosen for the present study. 
The unprecedented size and scale of the ongoing Ebola disease outbreak that started in December 
2013 in Guinea and subsequently spread to Sierra Leone, Nigeria and Liberia, led to the outbreak 
being declared a public health emergency of international concern in August 2014 by the WHO. 
This study is one of a series of studies to evaluate the heterologous combination of Ad26.ZEBOV 
and MVA-BN-Filo as a possible vaccine regimen to prevent Ebola disease. It will test schedules 
that are being evaluated in ongoing NHP challenge and Phase 1 clinical studies. 
In this Phase 2 study, the sponsor’s Ad26 vector expressing the EBOV Mayinga GP 
(Ad26.ZEBOV) and the MVA-BN vector with EBOV, SUDV and MARV GP inserts and TAFV 
NP insert (MVA-BN-Filo) will be evaluated as a heterologous prime-boost regimen. The first 
schedule to be evaluated is prime vaccination with MVA-BN-Filo followed by a boost with 
Ad26.ZEBOV 14 days later. In the second schedule, Ad26.ZEBOV is used to prime a filovirus-
specific immune response and MVA-BN-Filo is used to boost the immune response 28 days 
later. The EBOV GP that circulated in West Africa has 97% homology to the EBOV GP used in
this vaccine regimen.3
For the prevention of Ebola virus disease, short vaccination schedules may be relevant in the 
context of the epidemic and suitable for use during acute outbreaks of Ebola. When the current 
outbreak is under control, longer vaccination schedules may be more relevant than the shorter 
prime-boost intervals provided a more persistent immune response is observed. 
The 2 different time intervals (of 14 or 28 days) between the prime and the boost vaccination 
will be evaluated for safety and tolerability as well as for immunogenicity. These prime-boost 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
46
Status: Approved, Date: 18 September 2017
regimens will differ in the sequence of vaccination and timing of the boost vaccination 
depending on the sequence, while the dose of each vaccine will be identical. The vaccine 
consists of Ad26.ZEBOV at a dose of 5x1010 vp and 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.
The 14-, 28-day prime-boost intervals are being evaluated in the current Phase 1 studies. 
Preliminary data from a small group of healthy subjects in the VAC52150EBL1001 and 1002 
studies showed that both regimens, namely 14-day MVA prime/Ad26 boost regimen and 28-day 
Ad26 prime/MVA boost regimen, were immunogenic. 
This Phase 2 study will be conducted to enlarge the safety and immunogenicity database for the 
Ad26.ZEBOV and MVA-BN-Filo prime-boost regimens in healthy subjects and to extend the 
population studied in Phase 1 to include subjects up to and including 70 years of age and 
HIV-infected subjects. HIV-infected subjects are included in this study because they represent a 
significant minority population whose response to vaccination needs to be understood in order to 
develop an effective prophylactic vaccine against Ebola.
2.
OBJECTIVES AND HYPOTHESIS
2.1.
Objectives
Primary Objectives
The primary objectives are:

To assess the safety and tolerability of different vaccination schedules of Ad26.ZEBOV and 
MVA-BN-Filo administered IM as heterologous prime-boost regimens in healthy and in 
HIV-infected adults, with Ad26.ZEBOV prime and MVA-BN-Filo boost vaccination on 
Days 1 and 29, respectively and MVA-BN-Filo prime and Ad26.ZEBOV boost vaccination 
on Days 1 and 15, respectively.

To assess the immune responses to the EBOV GP (as measured by ELISA antibody 
concentration) of different vaccination schedules of Ad26.ZEBOV and MVA-BN-Filo 
administered IM as heterologous prime-boost regimens in healthy and in HIV-infected 
adults, with Ad26.ZEBOV prime and MVA-BN-Filo boost vaccination on Days 1 and 29,
respectively and MVA-BN-Filo prime and Ad26.ZEBOV boost vaccination on Days 1 and 
15, respectively.
Secondary Objective
To 
compare 
safety 
and 
tolerability 
of 
both 
Ad26.ZEBOV/MVA-BN-Filo 
and 
MVA-BN-Filo/Ad26.ZEBOV regimens between healthy and HIV-infected adults.

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Exploratory Objectives
The exploratory objectives include the following. Some exploratory objectives may not be 
performed if reagents or assays are not available.

To assess the humoral immune responses further regarding kinetics and durability as well as 
neutralizing antibody responses directed against EBOV GP induced by the heterologous 
prime-boost regimen as measured by a virus neutralization assay, at relevant time points of 
different vaccination schedules of Ad26.ZEBOV and MVA-BN-Filo.

To assess the kinetics and durability of cellular immune responses in healthy and 
HIV-infected adults for EBOV GP, by vaccine regime.

To compare kinetics and durability of humoral and cellular immune responses to EBOV GP 
of Ad26.ZEBOV/MVA-BN-Filo and MVA-BN-Filo/Ad26.ZEBOV regimens between 
healthy and HIV-infected adults.

To assess the kinetics and durability of humoral immune responses, including the 
development of neutralizing antibodies, in healthy and HIV-infected adults for other 
filovirus GP.

To assess the kinetics and durability of cellular immune responses in healthy and 
HIV-infected adults for other filovirus GP.

To compare kinetics and durability of humoral and cellular immune responses to other 
filovirus GP, of Ad26.ZEBOV/MVA-BN-Filo and MVA-BN-Filo/Ad26.ZEBOV regimens 
between healthy and HIV-infected adults.

To assess the frequency, magnitude, and durability of anti-vector responses in healthy and 
HIV-infected adults.

To compare kinetics and durability of humoral and cellular immune responses to the EBOV
and other filovirus GP of Ad26.ZEBOV/MVA-BN-Filo and MVA-BN-Filo/Ad26.ZEBOV
regimens between adults aged 18-50 and aged 51-70.

To assess the impact of CD4+ count on safety and immunogenicity of Ad26.ZEBOV/MVA-
BN-Filo and MVA-BN-Filo/Ad26.ZEBOV regimens in HIV-infected adults.

To assess changes in HIV RNA and HIV specific immune response (using HIV antigens in 
place of Ebola GP) associated with vaccination with Ad26.ZEBOV/MVA-BN-Filo and 
MVA-BN-Filo/Ad26.ZEBOV regimens in HIV-infected adults.

To assess humoral immune responses in genital, rectal and oral secretions in a subset of 
healthy and HIV-infected adults at selected sites for EBOV and other filovirus GP.

To explore the impact of host genetics on immune responses to the Ad26.ZEBOV/MVA-
BN-Filo and MVA-BN-Filo/Ad26.ZEBOV
prime-boost regimens in healthy
and 
HIV-infected adults.

To assess immune epitope breadth elicited by the Ad26.ZEBOV/MVA-BN-Filo and MVA-
BN-Filo/Ad26.ZEBOV prime-boost regimens in healthy and HIV-infected adults.

To assess the immunoglobulin subclass, glycosylation and effector functions of humoral 
responses to EBOV and other filovirus GP.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Status: Approved, Date: 18 September 2017

To describe B cell, helper T cell, and cytotoxic T cell responses elicited by the 
Ad26.ZEBOV/MVA-BN-Filo and MVA-BN-Filo/Ad26.ZEBOV prime-boost regimens in 
healthy and HIV-infected adults.

To explore immune inflammatory responses elicited by the Ad26.ZEBOV/MVA-BN-Filo 
and MVA-BN-Filo/Ad26.ZEBOV regimens in healthy and HIV-infected adults on a 
multiplex array platform to evaluate cytokine and soluble factor responses to vaccination.
2.2.
Hypothesis
No formal statistical hypothesis testing is planned for this study. The primary purpose of the 
study is to provide descriptive information regarding safety and immunogenicity of the 
2 vaccination regimens within cohorts of healthy and HIV-infected subjects. 
3.
STUDY DESIGN AND RATIONALE
3.1.
Overview of Study Design
This is a randomized, observer-blind, placebo-controlled, parallel-group, multicenter, 2-part, 
Phase 2 study to evaluate the safety, tolerability and immunogenicity of different vaccination 
regimens using Ad26.ZEBOV at a dose of 5x1010 vp and MVA-BN-Filo at a dose of 1x108 Inf U
(nominal titer), administered IM. The first regimen to be evaluated is prime vaccination with 
MVA-BN-Filo followed by a boost vaccination with Ad26.ZEBOV 14 days later. The second 
regimen to be evaluated is prime vaccination with Ad26.ZEBOV followed by a boost 
vaccination with MVA-BN-Filo 28 days later. These regimens will be evaluated in healthy and 
HIV-infected adults.
A planned total of 575 subjects will be enrolled, with approximately 300 healthy subjects and 
275 HIV-infected subjects. Eligible subjects are those who have never received a candidate
Ebola vaccine and have no prior exposure to EBOV (including travel to epidemic Ebola areas 
less than 1 month prior to screening) or a diagnosis of Ebola virus disease.
There are 2 parts to this study that will run in parallel. Part 1 features 2 cohorts consisting of 
50 healthy adults and 25 HIV-infected adults, aged 18-70 years inclusive. Within each cohort, 
subjects will be randomized in a 4:1 ratio to receive Ad26.ZEBOV and MVA-BN-Filo or 
placebo: MVA-BN-Filo prime vaccination followed by Ad26.ZEBOV boost vaccination or 
placebo prime and boost vaccination 14 days later. Randomization will be done separately for 
healthy subjects and HIV-infected subjects. Part 1 will be conducted exclusively in the US at the 
WRAIR Clinical Research Center.
Part 2 of the study will investigate 2 vaccination regimens: Ad26.ZEBOV prime vaccination 
followed by MVA-BN-Filo boost vaccination 28 days later (Group 1) and MVA-BN-Filo prime 
vaccination followed by Ad26.ZEBOV boost vaccination 14 days later (Group 2). Group 1 
includes 2 cohorts consisting of 200 healthy adults and 200 HIV-infected adults, aged 
18-70 years inclusive, randomized in a 4:1 ratio to receive Ad26.ZEBOV and MVA-BN-Filo or 
placebo: Ad26.ZEBOV as prime vaccination followed by MVA-BN-Filo as boost vaccination or 
placebo prime and boost vaccination 28 days later. Group 2 includes 2 cohorts consisting of 
50 healthy adults and 50 HIV-infected adults, aged 18-70 years inclusive, randomized in a 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
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Status: Approved, Date: 18 September 2017
4:1 ratio to receive Ad26.ZEBOV and MVA-BN-Filo or placebo: MVA-BN-Filo prime 
vaccination followed by Ad26.ZEBOV boost vaccination or placebo prime and boost vaccination
14 days later, as shown in Figure 2 and Table 1. Randomization will be done separately for 
healthy subjects and HIV-infected subjects. Randomization of HIV-infected subjects in Part 2 
will be contingent upon acceptable safety data from HIV-infected subject from Part 1.
An IDMC will be commissioned for this study. Refer to Section 11.7 for details.
Within each part, study-site personnel (except for those with primary responsibility for study 
vaccine preparation and dispensing), sponsor personnel and subjects will be blinded to the study 
vaccine allocation until all subjects in that part have completed the 6-month post-boost visit or 
discontinued earlier and the database has been locked for that part. For any interim analyses 
performed in a part before database lock, study-site personnel (except for those with primary 
responsibility for study vaccine preparation and dispensing), the sponsor (except for specifically 
designated sponsor personnel who are independent of the study) and subjects will remain blinded 
to study vaccine allocation. Refer to Section 5 for further details on blinding in case of interim 
analyses.
All subjects will receive the study vaccine (Ad26.ZEBOV, MVA-BN-Filo or placebo) IM in the 
deltoid muscle. In Part 1 and Part 2, Group 2, all subjects will receive MVA-BN-Filo 
(1x108 Inf U, nominal titer) or placebo on Day 1 followed by Ad26.ZEBOV (5x1010 vp) or 
placebo on Day 15. In Part 2, Group 1, all subjects will receive Ad26.ZEBOV (5x1010 vp) or 
placebo on Day 1, followed by MVA-BN-Filo (1x108 Inf U, nominal titer) or placebo on Day 29. 
The study consists of a screening phase of up to 8 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 Day 15 or 29, and a post-boost follow-up phase of maximum 
1 year post-boost vaccination. When all subjects in a part have completed the 6-month post-boost
visit or discontinued earlier, and the database for that part has been locked, the part will be 
unblinded. At that time, the subjects who received placebo in that part will be informed that they 
have completed the study and no further follow-up is required. However, subjects who received 
placebo and reach the 1-year post-boost visit (Part 1 and Part 2, Group 2: Day 380; Part 2, 
Group 1: Day 394) prior to unblinding will be required to attend the 1-year post-boost visit. The 
subjects who received Ad26.ZEBOV and MVA-BN-Filo will continue the study until the 1-year
post-boost vaccination visit to assess long-term safety and immunogenicity.
While Part 1 was enrolling, the sponsor halted all vaccinations in this study due to the occurrence 
of a serious and very rare condition, Miller Fisher syndrome, reported in study 
VAC52150EBL2001, until a revised ICF was prepared, and approval to restart the current study 
was granted by the relevant competent authority. As a result of the delay, some subjects in Part 1
may reach the Day 380 visit prior to unblinding of Part 1. Female subjects in Part 2 who became 
pregnant with estimated conception within 28 days after vaccination with MVA-BN-Filo (or 
placebo) or within 3 months after vaccination with Ad26.ZEBOV (or placebo) (unless local 
regulations have additional requirements for follow up) and children born to vaccinated female 
subjects in Part 2 who became pregnant with estimated conception within 28 days after 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
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Status: Approved, Date: 18 September 2017
vaccination with MVA-BN-Filo (or placebo) or within 3 months after vaccination with 
Ad26.ZEBOV (or placebo) will be eligible for enrollment into the VAC52150EBL4001 Vaccine 
Development Roll-over study for long-term surveillance (for a total of up to 60 months after the 
prime vaccination). After unblinding, only female subjects and children born to female subjects 
(with estimated conception within the period stated above) in Part 2 who received Ad26.ZEBOV 
and/or MVA-BN-Filo will be approached to consent for enrollment in the VAC52150 Vaccine 
Development Roll-over study for long-term surveillance. After unblinding, female subjects and 
children born to female subjects (with estimated conception within the period stated above) in 
Part 2 who received placebo and had already been enrolled into the VAC52150 Vaccine 
Development Roll-over study will be discontinued from further participation in the roll-over 
study.
As of amendment 4 implementation, no subjects in Part 1 will be approached anymore in this 
study to roll-over to the VAC52150EBL4001 study.
In the event that the study is paused in the future, subjects who were primed and awaiting boost 
will be followed every 3 months until 1 year for ascertainment of serious adverse events and 
IREs. Subjects who received both prime and boost will continue to follow the protocol as 
written. Subjects who are awaiting prime vaccination may need to be rescreened under a new 
subject number, repeating all screening procedures except the test of understanding (TOU)
(unless the TOU has been revised in the meantime, in which case it needs to be taken again).

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
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Status: Approved, Date: 18 September 2017
A schematic overview of the study design is presented in Figure 2.
Figure 2:
Schematic Overview of the Study 
HIV+: HIV-infected; pbo: placebo;
: time of interim analysis; ▼: time of final analysis
The baseline visit may be scheduled as soon as the results of all screening assessments are 
known (but should occur within 8 weeks from screening, see Section 9.1.2) and show that the 
subject is eligible for inclusion. The administration of the prime vaccination will occur on Day 1 
(baseline), after the completion of all baseline assessments.
All subjects will receive the study vaccine (Ad26.ZEBOV, MVA-BN-Filo or placebo) IM
(0.5 mL) in the deltoid muscle: 

Ad26.ZEBOV (5x1010 vp) on Day 1, followed by a boost vaccination of MVA-BN-Filo 
(1x108 Inf U) on Day 29 (Part 2, Group 1) OR

MVA-BN-Filo (1x108 Inf U) on Day 1, followed by a boost vaccination of Ad26.ZEBOV 
(5x1010 vp) on Day 15 (Part 1 and Part 2, Group 2)

Placebo (0.9% saline) on Day 1, followed by a boost vaccination of placebo (0.9% saline) 
on Day 15 or 29.
Refer to Section 6 for further details on dosage and administration. After each vaccination, 
subjects will remain at the site for a total of 30 (±10) minutes post-vaccination to monitor for the 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL2003 Amendment 5
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Status: Approved, Date: 18 September 2017
development of any acute reactions, or longer if deemed necessary by the investigator (eg, in 
case of grade 3 adverse events). 
Safety will be assessed by collection of solicited local and systemic adverse events 
(reactogenicity), unsolicited adverse events, serious adverse events, and IREs. The subjects will 
be closely observed by study-site personnel for 30 (±10) minutes after each 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). Any unsolicited, solicited local or systemic 
adverse events occurring while on site will be documented. Upon discharge from the site, 
subjects will receive a diary, a thermometer and a ruler to measure body temperature and 
solicited local reactions. Subjects will be instructed to record solicited local and systemic adverse 
events in the diary in the evening after each vaccination and then daily for the next 7 days at 
approximately the same time each day. Diaries should be completed at home by the subject. For 
subjects having difficulty completing the diary independently, the sites will make arrangements 
to have the diary completed according to their local practice. The investigator will document 
unsolicited adverse events from signing of the ICF 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). Adverse events that are ongoing at 42 days post-boost 
vaccination will be followed until resolution or stabilization. Other safety assessments include
physical examination, vital signs (blood pressure, pulse/heart rate, body temperature), clinical 
laboratory and pregnancy testing. 
The investigators, together with the sponsor’s study responsible physician, will be responsible 
for the safety monitoring of the study, and will halt vaccination of further subjects in case any of 
the pre-specified pausing rules described in Section 9.3.2 have been met or in case of other 
severe safety concerns. 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). Discontinuation of study 
vaccine should occur in any subject meeting the criteria outlined in Section 10.2.
In addition, the investigator will collect samples for immunogenicity assessments at the time 
points indicated in the Time and Events Schedule. Samples to assess humoral responses and 
samples to assess cellular immune responses will be taken from all subjects. In Part 2, a subset of 
approximately 40% will also participate in the optional mucosal assessments. Subjects giving 
informed consent for the study will be informed that their leftover blood and secretion samples 
will be stored for potential future research. Subjects can withdraw consent for their samples to be 
used for future research at any time (see Section 16.2.6).
An interim analysis will be conducted when all subjects in Part 1 have completed the 21-day 
post-boost visit, or discontinued earlier. The purpose of this interim analysis is to evaluate the 
effect of vaccination on the HIV viral load of HIV-infected subjects from a safety perspective. 
This interim analysis will be reviewed by the Protocol Safety Review Team (PSRT) and 
forwarded to the IDMC for review. An additional interim analysis will be done when all subjects 
in Part 1 have completed the 1-year post-boost visit or discontinued earlier. 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Status: Approved, Date: 18 September 2017
Additional (ad hoc) interim analyses may be performed during the study 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 unless a significant safety concern has been identified.
The final analysis will be performed when all subjects have completed the last study-related visit 
or discontinued earlier.
After completing the present study, female subjects who became pregnant with estimated 
conception within timelines as indicated before and children born to female subjects (with 
estimated conception within the period stated above) in Part 2 will be approached to consent for 
enrollment into the VAC52150 Vaccine Development Roll-over study for long-term surveillance 
(see Section 9.1.5 for details).
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 regimen to provide a robust safety and immunogenicity database 
to support registration. Further, preliminary data on the 14-day MVA prime/Ad26 boost regimen
from ongoing Phase 1 studies have shown this regimen to be immunogenic and thus appropriate 
to consider for use in an outbreak setting. This study proposes to satisfy these development 
objectives: enlarge the safety and immunogenicity database in adults, contribute to the safety and 
immunogenicity data in HIV-infected adults and enhance the experience of the 14-day 
MVA/Ad26 prime/boost regimen.
Control and Blinding
Randomization will be used to minimize bias in the assignment of subjects to vaccination 
schedules (groups), to increase the likelihood that known and unknown subject attributes 
(eg, demographic and baseline characteristics) are evenly balanced across groups, and to enhance 
the validity of possible statistical comparisons across groups.
In addition, randomization will be used to minimize bias in the assignment of subjects to study 
vaccine (Ad26.ZEBOV and MVA-BN-Filo versus placebo). Placebo recipients are included for 
blinding purposes and safety analyses, and will provide control specimens for immunogenicity 
assays. A placebo control will be used up to 6 months post-boost to establish the frequency and 
magnitude of changes in clinical and immunologic endpoints that may occur in the absence of 
the Ad26.ZEBOV and MVA-BN-Filo. The nature of the study vaccine (active versus placebo) 
will be blind to reduce potential bias during data collection and evaluation of clinical safety 
endpoints. Blinding will be guaranteed by preparation of study vaccine by unblinded qualified 
study-site personnel not involved in any other study-related procedure, and by the administration 
of vaccine in a masked syringe by a blinded vaccine administrator (see Definitions of Terms). No 
additional placebo injections will be administered to mask the vaccination schedule across 
groups.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Status: Approved, Date: 18 September 2017
Study Groups
There are two vaccination schedules being investigated in this study. One schedule, 
MVA-BN-Filo prime followed by Ad26.ZEBOV 14 days later, is being studied in Part 1 and 
Part 2, Group 2. The other schedule, Ad26.ZEBOV prime followed by MVA-BN-Filo 28 days 
later, is being studied in Part 2, Group 1. The dose of each vaccine, regardless of the order of 
administration, remains the same. The dose of Ad26.ZEBOV is 5x1010 vp and the dose of 
MVA-BN-Filo is 1x108 Inf U, which corresponds to the dose of 1x108 TCID50 that is used in the 
current Phase 1 studies. The safety, tolerability and immunogenicity results for the 2 vaccination 
schedules will be evaluated in the study. 
The study population consists of healthy subjects and HIV-infected subjects, both allocated to 
the different vaccination schedules in Part 2. This will allow for evaluation of the vaccine 
schedules in both populations.
Future Research
Subjects giving informed consent for the study will be informed that their leftover blood and 
secretion samples (serum and/or peripheral blood mononuclear cells [PBMC]) will be stored for 
potential future research (see Section 16.2.6). 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 will be performed within 8 weeks before administration of 
study vaccine on Day 1. Subjects must sign an ICF indicating that he or she understands the 
purpose of and procedures required for the study and is willing to participate in the study. 
Signing of the ICF needs to be done before the first study-related activity.
The inclusion and exclusion criteria for enrolling subjects in this study are described in the 
following 2 subsections. If there is a question about the inclusion or exclusion criteria below, the 
investigator must consult with the appropriate sponsor representative and resolve any issues 
before enrolling a subject in the study. Waivers are not allowed.
For a discussion of the statistical considerations of subject selection, refer to Section 11.1, 
Sample Size Determination.
NOTE: The investigator should ensure that all study enrollment criteria have been met at the end 
of the screening period. If a subject’s clinical status changes (including any available laboratory 
results or the receipt of additional medical records) after screening but before Day 1 so the 
subject no longer meets the eligibility criteria, then the subject should be excluded from further 
participation in the study. Section 17.4 describes the required documentation to support meeting 
the enrollment criteria.

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Status: Approved, Date: 18 September 2017
4.1.
Inclusion Criteria 
4.1.1.
Inclusion Criteria for Healthy Adult Subjects
Each potential subject must satisfy all of the following criteria to be enrolled in the study.
1.
Each subject must sign an ICF indicating that he or she understands the purpose of and 
procedures required for the study and is willing to participate in the study. In case the 
subject cannot read or write, the procedures must be explained and informed consent 
must be witnessed by a literate third party not involved with the conduct of the study.
2.
Subject must be a man or woman aged 18 to 70 years of age, inclusive at screening.
3.
Subject must be healthy in the investigator’s clinical judgment on the basis of medical 
history, physical examination and vital signs performed at screening.
4.
Subject must be healthy on the basis of clinical laboratory tests and ECG (only in 
subjects >50 years) performed at screening. If the results of the laboratory screening tests
and ECG are outside the institutional normal reference ranges, the subject may be 
included only if the investigator judges the abnormalities or deviations from normal to be 
not clinically significant or to be appropriate and reasonable for the population under 
study. This determination must be recorded in the subject's source documents and 
initialed by the investigator. However, the subject should not be included when 
hemoglobin is lower than the institutional normal reference range (or below the values in 
Attachment 3 when that range is not available).
Note: The safety laboratory assessments at screening are to be performed within 28 days 
prior to the prime vaccination and may be repeated if they fall outside this time window.
Note: In case of menstruation, urinalysis must be postponed but a result should be 
available before the prime vaccination. All urinalyses should be collected as freshly 
voided, mid-stream, clean catch samples obtained after proper cleansing.
Note: If laboratory screening tests are out of range and deemed clinically significant, 
repeat of screening tests is permitted only once using an unscheduled visit during the 
screening period to assess eligibility.
5.
Criterion modified per Amendment 3.
5.1 Contraceptive use by women should be consistent with local regulations regarding the use 
of contraceptive methods for subjects participating in clinical studies.
Before randomization (on Day 1), subjects who were born female must be either:
a. Of childbearing potential and practicing a highly effective method of birth control 
consistent with local regulations regarding the use of birth control methods for 
subjects participating in clinical studies, beginning at least 28 days prior to 
vaccination until at least 3 months after the boost vaccination. The sponsor considers 
the following methods of birth control to be highly effective: established use of oral, 
injected or implanted hormonal methods of contraception; placement of an 
intrauterine device or intrauterine system; barrier methods (condom or occlusive cap 
[diaphragm 
or 
cervical/vault 
caps] 
with
spermicidal 
foam/gel/film/cream/suppository); male partner sterilization (the vasectomized 

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Clinical Protocol VAC52150EBL2003 Amendment 5
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Status: Approved, Date: 18 September 2017
partner should be the sole partner for that subject). More restrictive measures may 
be required by the site. 
Note: Reliance on abstinence or natural family planning are not acceptable birth 
control methods for sexually active women of child-bearing potential. 
b. Not of childbearing potential defined as: 
o
postmenopausal 
A postmenopausal state is defined as >45 years of age with amenorrhea for at 
least 2 years
o
permanently sterile
Permanent sterilization methods include bilateral tubal occlusion (which 
includes tubal ligation procedures as consistent with local regulations), 
hysterectomy, bilateral salpingectomy, bilateral oophorectomy
o
incapable of pregnancy. 
Note: If the social situation of a woman changes after start of the study (eg, woman who 
is not heterosexually active becomes active), she must begin a highly effective method of 
birth control, as described above.
6.
A woman of childbearing potential must have a negative urine β-human chorionic 
gonadotropin -hCG) pregnancy test at screening and a negative urine -hCG pregnancy 
test immediately prior to each study vaccine administration.
Note: If the pregnancy test result is positive, in order to maintain subject confidentiality, 
the investigator will ensure adequate counseling and follow-up will be made available.
7.
A man who is sexually active with a woman of childbearing potential must be willing to 
use condoms for sexual intercourse beginning prior to prime vaccination until at least 
3 months after the boost vaccination, unless a vasectomy was performed more than 1 year 
prior to screening.
8.
Subject must be available and willing to participate for the duration of the study visits 
and follow-up.
9.
Subject must be willing and able to comply with the protocol requirements, including the 
Prohibitions and Restrictions specified in Section 4.3.
10. Subject must be willing to provide verifiable identification.
11. Subject must have a means to be contacted.
12. Subject must pass the TOU (passing score: ≥90%) (Attachment 1).
Note: If subjects fail the TOU test on the first attempt, subjects must be retrained on the 
purpose of the study and must take the test again (2 repeats are allowed). If subjects fail 
on the third attempt, they should not continue with the consenting and screening 
processes.

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Status: Approved, Date: 18 September 2017
4.1.2.
Additional Inclusion Criteria for HIV-infected Subjects
All of the inclusion criteria for healthy adult subjects (see Section 4.1.1) must be met by adults 
who are HIV-infected with the following additions/clarifications:
13. Subjects must have a positive HIV-1 and/or -2 serology test within 6 months of 
screening, including the day of screening.
14. Subjects must have a screening CD4+ cell count >200 cells/µL
15. Criterion modified per Amendment 3.
15.1 Investigators should use their best clinical judgment when determining stability of highly 
active antiretroviral therapy (HAART). The occasional missed dose would not make a 
subject ineligible for the study. In uncertain cases, the subject’s eligibility should be 
discussed with the sponsor.
Part 1: All subjects must be on a stable HAART regimen for 4 weeks prior to screening, 
taking into account the following criteria.
Part 2: Subjects with screening CD4+ cell count <350 cells/µL must be on a stable 
HAART regimen for 4 weeks prior to screening, taking into account the following
criteria:

Antiretroviral therapy (ART) is considered stable if subjects did not change their 
antiretroviral drugs within the last 4 consecutive weeks prior to their first screening 
visit. Changes in formulations are allowed.

Subject must be willing to continue their ART throughout the study as directed by their 
local physician.
Subjects newly diagnosed with HIV infection at screening must be referred for 
continuing care and if started on therapy, they must be rescreened using a new subject 
number with repeat laboratory testing (see Section 9.1.2) after they have been on that 
regimen for 4 weeks.
16. Subject must be in an otherwise reasonably good medical condition (absence of acquired 
immunodeficiency syndrome [AIDS]-defining illnesses or clinically significant disease), 
diagnosed on the basis of physical examination, medical history and the investigator’s 
clinical judgment at the time of screening (refer to Section 4.1.1 for details).
Note for Part 2 subjects: Otherwise healthy HIV-infected individuals with CD4+ cell 
count ≥350 cells/µL who are not taking ART may be eligible for the study if they are 
engaged in ongoing HIV care and meet all other enrollment criteria.

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4.2.
Exclusion Criteria 
4.2.1.
Exclusion Criteria for Healthy Adult Subjects
Any potential subject who meets any of the following criteria will be excluded from participating 
in the study. 
1. Has received any candidate Ebola vaccine.
2. Diagnosed with Ebola virus disease, or prior exposure to EBOV, including travel to 
epidemic Ebola areas less than 1 month prior to screening. 
Note: Participation of international volunteers to Ebola operations is allowed, but they 
should comply with the prohibitions and restrictions as specified in Section 4.3.
3. Has received any experimental candidate Ad26- or MVA-based vaccine in the past or 
received any other investigational drug or investigational vaccine or used an invasive 
investigational medical device within 3 months prior to screening.
Note: Receipt of any approved vaccinia/smallpox vaccine or Ad-based candidate vaccine 
other than Ad26 at any time prior to study entry is allowed.
4. Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or 
vaccine products (including any of the constituents of the study vaccines 
[eg, polysorbate 80, ethylenediaminetetraacetic acid (EDTA) or L-histidine for 
Ad26.ZEBOV vaccine; tris (hydroxymethyl)-amino methane (THAM) for MVA-BN-Filo 
vaccine]), including known allergy to egg, egg products and aminoglycosides.
5. Subject with acute illness (this does not include minor illnesses such as diarrhea or mild 
upper respiratory tract infection) or body temperature ≥38.0ºC on Day 1 will be excluded 
from prime vaccination at that time, but may be rescheduled for prime vaccination at a 
later date.
6. HIV type 1 or type 2 infection.
Note: If the HIV test result is positive, in order to maintain subject confidentiality, the 
investigator will ensure adequate counseling and follow-up will be made available.
7. A woman who is pregnant, breast-feeding or planning to become pregnant while enrolled 
in the study or within at least 3 months after the boost vaccination.
8. Presence of significant conditions (eg, history of seizure disorders, (auto)immune disease 
or deficiency, any spleen disease, active malignancy, ongoing tuberculosis treatment, 
other systemic infections) or clinically significant findings during screening of medical 
history, ECG (only in subjects >50 years), physical examination, vital signs or laboratory 
testing for which, in the opinion of the investigator, participation would not be in the best 
interest of the subject (eg, compromise the safety or well-being) or that could prevent, 
limit, or confound the protocol-specified assessments.

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Note: Subjects who have recently received treatment for acute, uncomplicated malaria 
are eligible for randomization if at least 3 days have elapsed from the conclusion of a 
standard, recommended course of therapy for malaria; subjects who are acutely ill with 
malaria at the time of the initial screening should complete therapy and wait an 
additional 3 days after completion before they can enter the screening phase for the 
study.
Note: Subjects with sickle cell trait can be included.
9. History of or underlying liver or renal insufficiency, or significant cardiac, vascular, 
pulmonary (eg, persistent asthma), gastrointestinal, endocrinic, neurologic, hematologic, 
rheumatologic, psychiatric or metabolic disturbances or eczema.
10. History of malignancy other than squamous cell or basal cell skin cancer, unless there has 
been surgical excision that is considered cured. Subjects with malignancies who are 
currently being treated or are not surgical cures are excluded.
11. Major surgery (per the investigator’s judgment) within the 4 weeks prior to screening or 
planned major surgery through the course of the study (from screening until completion 
of the study, see Section 10.1).
12. Post-organ and/or stem cell transplant whether or not with chronic immunosuppressive 
therapy.
13. Receipt of any disallowed therapies as noted in Section 8 before the planned 
administration of the prime vaccine on Day 1.
14. Is currently participating in or planning to participate in another clinical study during the 
study. 
Note: Participation in an observational clinical study is allowed.
15. Donation of a unit of blood within 8 weeks before Day 1 or plan to donate blood until 
42-days post-boost.
16. Receipt of blood products or immunoglobulin within 3 months prior to screening and 
during participation in the study.
17. Current or past abuse of alcohol, recreational or narcotic drugs, which in the 
investigator’s opinion would compromise the subject’s safety and/or compliance with the 
study procedures.
18. History of chronic urticaria (recurrent hives).
19. Subject cannot communicate reliably with the investigator.
20. Subject who, in the opinion of the investigator, is unlikely to adhere to the requirements 
of the study.
21. Employee of the investigator or study site, with direct involvement in the proposed study 
or other studies under the direction of that investigator or study site, as well as family 
members of the employees or the investigator. 

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4.2.2.
Additional Exclusion Criteria for HIV-infected Subjects
HIV-infected subjects must not meet any of the exclusion criteria for healthy adult subjects (see 
Section 4.2.1) with the exception of exclusion criterion 6: HIV-1 or HIV-1/2 infection.
HIV-infected subjects must have a positive HIV-1 or HIV-1/2 test within 6 months of screening, 
including the day of screening.
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. Female subjects of childbearing potential must remain on a highly effective method of 
birth control consistent with local regulations regarding the use of birth control methods 
for subjects participating in clinical studies (see inclusion criteria) until at least 3 months 
after the boost vaccination. If the social situation of a female subject changes after start of 
the study (eg, female subject who is not heterosexually active becomes active), she must 
begin a highly effective method of birth control, as described above in Sections 4.1 and
4.2, until at least 3 months after the boost vaccination.
Note: Prior to each study vaccine administration, a urine pregnancy test should be 
performed for female subjects of childbearing potential.
2. Male subjects who did not have a vasectomy performed more than 1 year prior to 
screening and who are sexually active with a female subject of childbearing potential 
must use condoms for sexual intercourse until at least 3 months after the boost
vaccination.
3. Women should not breast-feed while enrolled in the study until at least 3 months after the 
boost vaccination.
4. Traveling to epidemic Ebola areas is prohibited while enrolled in the study from the start 
of screening onwards until the 6-month post-boost visit. Subjects who subsequently travel 
to these areas should have returned at least 1 month before the 1-year post-boost visit. 
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 4.2.1).
5. Subjects should not use any disallowed therapies as described in Section 8.
5.
TREATMENT ALLOCATION AND BLINDING
Vaccination Schedule Allocation
Central randomization will be implemented in this study. The randomization within each group 
will be balanced by using randomly permuted blocks. There will be stratification by age group 
(subjects ≥18 to ≤50 years versus subjects >50 years). The interactive web response system 
(IWRS) will assign a unique code, which will dictate the assignment and matching vaccination 

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schedule for the subject. The requestor must use his or her own user identification and personal 
identification number when contacting the IWRS, and will then give the relevant subject details 
to uniquely identify the subject.
For Part 1, subjects will be randomized in a 4:1 ratio to either receive MVA-BN-Filo or placebo 
on Day 1 followed by a boost vaccination of Ad26.ZEBOV or placebo 14 days later.
Randomization will be done separately for healthy subjects (N=50) and HIV-infected subjects
(N=25).
Part 2 will be conducted in parallel to Part 1 but has a different randomization scheme. In Part 2, 
a subject will be randomly enrolled in 1 of 2 groups at study entry in a 4:1 ratio of Group 1
versus Group 2. Within each group, subjects will be randomized in a 4:1 ratio to receive 
Ad26.ZEBOV and MVA-BN-Filo versus placebo. Randomization will be done separately for 
healthy subjects (N=250) and HIV-infected subjects (N=250). Randomization of HIV-infected 
subjects in Part 2 will be contingent upon acceptable safety data from HIV-infected subjects
from Part 1.
Blinding
For each part, subjects and study-site personnel will be blinded to the study vaccine allocation 
until the last subject in that part has completed the 6-month post-boost visit or discontinued 
earlier and the database has been locked for that part, 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 
blinded study vaccine administrator (see Definitions of Terms).
When all subjects in a part have completed the 6-month post-boost visit or discontinued earlier
and the database for that part has been locked the part 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 1-year post-boost visit (Part 1 and Part 2, Group 2: Day 380; Part 2, Group 1: Day 394) prior 
to unblinding will be required to attend the 1-year post-boost visit. Subjects who received 
Ad26.ZEBOV and MVA-BN-Filo will be followed up in an open-label fashion until the 1-year 
post-boost visit. For any interim analyses performed in a part before database lock, study-site
personnel (except for those with primary responsibility for study vaccine preparation and 
dispensing), the sponsor (except for specifically designated sponsor personnel who are 
independent of the study) and subjects will remain blinded to study vaccine allocation (see 
below). Refer to Sections 3.1 and 11 for further details on unblinding and interim analyses.
The investigator will not be provided with randomization codes. The codes will be maintained 
within the IWRS, which has the functionality to allow the investigator to break the blind for an 
individual subject.
Data that may potentially unblind the study vaccine assignment (ie, study vaccine 
preparation/accountability data, or other specific laboratory data) will be handled with special 
care to ensure that the integrity of the blind is maintained and the potential for bias is minimized. 

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This can include making special provisions, such as segregating the data in question from view 
by the investigators, clinical team, or others as appropriate until the time of database lock and 
unblinding. The pharmacy and preparation of study vaccines will be monitored by an 
independent study vaccine monitor (see Section 17.8).
Under normal circumstances, the blind should not be broken in a part, until all subjects in that 
part completed the 6-month post-boost visit or discontinued earlier and the database has been 
locked for that part. 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 treatment 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 a part if all subjects in that part
completed the 6-month post-boost visit or discontinued earlier. For any interim analysis
performed in a part before database lock, 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 further study vaccine administration (only applicable for subjects in the 
vaccination phase) and must be followed as appropriate (see Section 10.2 for details). If the 
randomization code is broken by the sponsor for safety reporting purposes, the subject should not 
discontinue further study vaccine administration and may remain in the study (if the 
randomization code is still blinded to the study-site personnel and the subject).

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6.
DOSAGE AND ADMINISTRATION
An overview of the study vaccination schedules is provided in Table 1.
Table 1:
Study Vaccination Schedules Parts 1 and 2
Part 1: US, n=75
MVA-BN-Filo prime day 1, Ad26.ZEBOV boost day 15
Active
Placebo
Healthy Adult
HIV+ Adult
Healthy Adult
HIV+ Adult
40
20
10
5
Part 2: Africa, n=500
Group 1: Ad26.ZEBOV prime day 1, MVA-BN-Filo boost day 29
Active
Placebo
Healthy Adult
HIV+ Adult
Healthy Adult
HIV+ Adult
160
160
40
40
Group 2: MVA-BN-Filo prime day 1, Ad26.ZEBOV boost day 15
Active
Placebo
Healthy Adult
HIV+ Adult
Healthy Adult
HIV+ Adult
40
40
10
10
6.1.
General Instructions and Procedures
All subjects will receive a vaccination, according to randomization, on Day 1 and on Day 15 
(Part 1 and Part 2, Group 2), or Day 29 (Part 2, Group 1) at the following dose levels:
Ad26.ZEBOV: 5x1010 vp, supplied in a single use vial (0.5 mL extractable)
MVA-BN-Filo: 1x108 Inf U (nominal titer; target fill is 1.9x108 Inf U per dose, range: 
1.27-2.67x108 Inf U), supplied in a single use vial (0.5 mL extractable)
Placebo: 0.9% saline (0.5 mL extractable)
Study vaccines (Ad26.ZEBOV, MVA-BN-Filo or placebo) will be administered as 0.5-mL IM 
injections into the deltoid muscle by a blinded study vaccine administrator. In each subject, the 
boost vaccination should preferably be administered in the opposite deltoid from the prime 
vaccination (unless local site reaction cannot be assessed reliably in the opposite arm) and it 
should be recorded in the CRF in which arm the vaccination has been administered. The 
injection site should be free from any injury, local skin problem, significant tattoo or other issue 
that might interfere with evaluating the arm after injection (eg, subjects with a history of skin 
cancer must not be vaccinated at the previous tumor site). No local or topical anesthetic will be 
used prior to the injection.
Discontinuation of study vaccine administration should occur in any subject meeting the criteria 
outlined in Section 10.2. Criteria for postponement of vaccination and contraindications to boost 
vaccination have been defined in Sections 6.2 and 6.3, respectively. Refer to Section 9.3.2 for 
details on the pre-specified pausing rules to halt vaccination of further subjects. 
After each vaccination, subjects will remain at the site for a total of 30 (±10) minutes 
post-vaccination to monitor for the development of any acute reactions, or longer if deemed 

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necessary by the investigator (eg, in case of grade 3 adverse events). As with any vaccine, 
allergic reactions following vaccination with the study vaccine are possible. Therefore, 
appropriate drugs and medical equipment to treat acute anaphylactic reactions must be 
immediately available and a medically qualified member of study-site personnel trained to 
recognize and treat anaphylaxis must be present in the clinic during the entire vaccination 
procedure and post-vaccination monitoring period.
The investigator must provide emergency care as needed for any subject who experiences a 
life-threatening event. All sites will have facilities, equipment and the ability to manage an 
anaphylactic reaction. If additional therapy is required, the investigator will arrange for transport 
to the closest appropriate facility for continuing care.
The Site Investigational Product Procedures Manual specifies the maximum time that will be 
allowed between preparation and administration of the study vaccine.
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)
Note: If a subject is acutely ill with malaria at the time of either prime or boost vaccination, 
at least 3 days must elapse from the conclusion of a standard, recommended course of 
therapy for malaria before vaccination.
Fever (body temperature ≥38.0°C) at the time of vaccination
Subjects experiencing any of the events described above may be vaccinated up to 10 days 
beyond the window allowed for the scheduled vaccination, or be withdrawn from that 
vaccination at the discretion of the investigator and after consultation with the sponsor (see 
Section 10.2).
Note: In case the boost 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 or she experiences any of the following 
events at any time after the prime vaccination: 
1. Any anaphylaxis that occurs between prime and boost vaccination either attributable to study 
vaccine or not OR
2. Generalized urticaria within 72 hours of vaccination considered to be at least possibly related 
to study vaccine OR
3. A serious adverse event considered to be at least possibly related to study vaccine OR

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4. Injection site ulceration, abscess or necrosis considered to be at least possibly related to the 
study vaccine OR
5. Any other safety concern threatening the subject’s safety or persisting clinically significant 
abnormality considered to be related to prime vaccination
Subjects experiencing any of the events described above must not receive any further study 
vaccine, but should be monitored for safety and for immunogenicity according to the protocol as 
described in Section 10.2.
An ad hoc IDMC meeting may be requested via the sponsor for any single event or combination 
of multiple events which are considered to jeopardize the safety of the subjects.
7.
TREATMENT COMPLIANCE
All study vaccines will be administered on site by a blinded study vaccine administrator (see 
Definitions of Terms). The date and time of each study vaccine administration will be recorded
in the CRF.
8.
PRESTUDY AND CONCOMITANT THERAPY
Prestudy therapies administered up to 30 days prior to the start of screening and previous 
vaccinia/smallpox vaccination at any time prior to study entry must be recorded in the CRF. 
Concomitant therapies must be recorded from screening onwards until the 42-day post-boost
visit. Concomitant therapies should also be recorded after the 42-day post-boost visit but only if 
given in conjunction with serious adverse events and IREs that meet the criteria outlined in 
Sections 12.3.2 and 12.3.3, respectively. Any vaccines received during the study should be 
recorded. 
All therapies (prescription or over-the-counter medications, including vaccines, vitamins, herbal 
supplements; non-pharmacologic therapies such as electrical stimulation, acupuncture, special 
diets, exercise regimens) must be recorded in the CRF. Recorded information will include a 
description of the type of the drug, treatment period, dosing regimen, route of administration, and 
its indication.
Subjects must use adequate birth control measures prior to randomization as described in 
Section 4.
Subjects are not allowed to have received any experimental candidate Ad26- or MVA-based 
vaccine in the past or received any other investigational drug or investigational vaccine or used 
an invasive investigational medical device within 3 months prior to screening. Receipt of any 
approved vaccinia/smallpox vaccine or Ad-based candidate vaccine other than Ad26 at any time 
prior to study entry is allowed.

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Subjects are allowed to receive all routine immunizations according to local vaccination 
schedules, taking into account the following restrictions:

Routine immunizations with inactivated vaccines should be administered at least 15 days 
before or after administration of any study vaccine to avoid any potential interference in 
efficacy of the routine immunizations or the interpretation of immune responses to study 
vaccines, as well as to avoid potential confusion with regard to attribution of adverse 
reactions. 

Routine immunizations with live attenuated vaccines are prohibited in the period from 
30 days before baseline (Day 1) to 30 days after the 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 nonsteroidal anti-inflammatory drugs may be used 
post-vaccination only in case of medical need (eg, body temperature ≥38.0 °C or pain) and their 
use must be documented. Use of these medications as routine prophylaxis within 24 hours 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. 
HAART must be documented as a prior medication and any changes to the subject's HAART 
regimen must also be recorded. HIV-infected subjects who begin the study untreated may begin 
an HAART regimen during the course of the study as indicated by local guidelines. Adherence to
HAART will be assessed at every visit.
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in 
which prohibited therapies are administered. Prohibited therapies will be captured as protocol 
deviations.
9.
STUDY EVALUATIONS
9.1.
Study Procedures
9.1.1.
Overview
The Time and Events Schedule summarizes the frequency and timing of safety, tolerability and 
immunogenicity measurements and evaluations applicable to this study. Details for all study 
procedures are provided in the following sections. Additional unscheduled study visits may be 
required if in the investigator’s opinion, further clinical or laboratory evaluation is needed.
Visit Windows
The screening visit has to be performed within 8 weeks prior to the baseline visit (ie, the day of 
the subject’s prime vaccination, Day 1). If a subject did not receive study vaccine on the planned 
day of vaccination, the timings of the next visits post-vaccination (see Time and 
Events Schedule) will be determined relative to the actual day of vaccination. Visit windows that 

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will be allowed are summarized in Table 2. The subject should be encouraged to come on the 
exact day planned and use the visit window only if absolutely necessary.
Table 2:
Visit Windows
Visit description
Day
Window 
7 Days Post-prime Vaccination 
Day 8 for all groups
±2 days
Boost Vaccination
Day 15 for Part 1 and Part 2, Group 2
Day 29 for Part 2, Group 1
±3 days
7 Days Post-boost Vaccination 
Day 22 for Part 1 and Part 2, Group 2
Day 36 for Part 1 and Part 2, Group 1
±2 days
21 Days Post-boost Vaccination
Day 36 for Part 1 and Part 2, Group 2
Day 50 for Part 2, Group 1
±3 days
42 Days Post-boost Vaccination 
Day 57 for Part 1 and Part 2, Group 2
Day 71 for Part 2, Group 1
±3 days
Follow-up 6 Months Post-boost
Day 195 for Part 1 and Part 2, Group 2
Day 209 for Part 2, Group 1
±15 days
Follow-up 1 Year Post-boost
Day 380 for Part 1 and Part 2, Group 2
Day 394 for Part 2, Group 1
±30 days
Blood Sampling Volumes
Approximately 571 to 675 mL of blood (including PBMC samples) will be drawn over a period 
of around 1 year, and remains well below the limits of standard blood donation. Additional blood 
may be drawn to confirm and follow-up on adverse events.
For details on the approximate blood sampling volumes collected by visit and the cumulative 
blood volumes, refer to the Time and Events Schedule. 
Additional urine pregnancy tests may be performed, as determined necessary by the investigator 
or required by local regulation, to establish the absence of pregnancy at any time during the 
subject's participation in the study.
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples.
9.1.2.
Screening Phase
Up to 8 weeks before baseline (the day of the subject’s prime vaccination, Day 1) and after 
signing and dating the ICF (see Section 16.2.4), screening assessments will be performed as 
indicated in the Time and Events Schedule. Screening may be split into multiple days or visits. In 
exceptional cases, the screening phase can be extended if discussed with and approved 
(documented) by the sponsor, eg, if not all the test results become available during the allocated
8 weeks; this will be evaluated on a case-by-case basis. Each site-specific addendum will 
identify an estimate of the number of subjects that may be screened, as this will vary across all 
sites (Section 17.12). If a subject is a screen failure, the subject may be rescreened on 1 occasion 
after consultation and agreement with the sponsor medical monitor and after a new informed 
consent has been obtained. Subjects who are rescreened will be assigned a new subject number 

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and will repeat all screening procedures, except TOU (unless the TOU has been revised in the 
meantime, in which case it needs to be taken again).
For male subjects and female subjects of non-childbearing potential, there will be no minimum 
duration of the screening period and it will last only for the time required to verify eligibility 
criteria. For female subjects of childbearing potential, it should be confirmed that adequate birth 
control measures were used from at least 28 days before the prime vaccination with a negative 
urine -hCG pregnancy test at screening and a negative urine pregnancy test immediately prior 
to each study vaccination (see Section 4). All male and female subjects, except for female 
subjects of non-childbearing potential, will be asked to use adequate birth control for sexual 
intercourse until at least 3 months after the boost vaccination (see Section 4.3).
Only subjects complying with the criteria specified in Section 4 will be included in the study. 
The investigator will provide detailed information on the study to the subject and will obtain 
written informed consent prior to each subject’s study participation. The procedures indicated in 
the Time and Events Schedule will only be performed after the subject’s written informed 
consent has been obtained. 
After reading but before signing the ICF, the TOU will be conducted (or as required per local 
regulations and practices). Subjects who fail may repeat the test twice (and have to pass the third 
time to be eligible). Subjects must pass the TOU before starting the screening procedures. The 
TOU is a questionnaire to document the subject’s understanding of the study (for details, see 
Section 16.1).
The following is performed to determine eligibility requirements as specified in the inclusion and 
exclusion criteria:
Review of all inclusion and exclusion criteria
Review of medical history (including concomitant diseases) and demographics
Review of prestudy therapies (up to 30 days prior to the start of screening), previous 
vaccinia/smallpox vaccination if known (at any time prior to study entry) and concomitant 
therapies
ECG recording (for subjects >50 years)
Urine pregnancy test (for female subjects of childbearing potential)
Full physical examination (including height and body weight; a genitourinary examination is 
not required)
Measurement of vital signs (blood pressure, pulse/heart rate, body temperature)
Blood sampling for hematology and chemistry (fasting or non-fasting)
Urinalysis
Serology testing: HIV type 1 or HIV type 1 and 2

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CD4+ cell count for HIV-infected subjects
All adverse events and pregnancies will be collected starting at the time a signed and dated ICF 
is obtained. Serious adverse events and IREs will be collected from signing of the ICF onwards 
until the end of the study.
The overall eligibility of the subject to participate in the study will be assessed once all screening 
values and results of any other required evaluations are available. Retesting of values (eg, safety 
laboratory) that lead to exclusion is allowed only once using an unscheduled visit during 
screening to assess eligibility. The safety laboratory assessments are to be performed within 
28 days prior to the prime vaccination and may be repeated once if they fall outside this time 
window. Study subjects who qualify for inclusion will be contacted and scheduled for enrollment 
and prime vaccination within 8 weeks.
9.1.3.
Vaccination Phase
If eligible, the subject will come for the baseline visit (Day 1). The investigator should ensure 
that all enrollment criteria have been met during screening. If a subject’s clinical status changes 
(including any available laboratory results or receipt of additional medical records) after 
screening but before the prime vaccination (Day 1) such that the subject no longer meets all 
enrollment criteria, then the subject should be excluded from further participation in the study. If 
the initial laboratory sampling for hematology, chemistry, urinalysis and urine pregnancy test 
occurred more than 28 days before baseline (Day 1), sampling will need to be repeated.
Eligible subjects will be allocated (by central randomization) to a vaccination schedule as 
described in Section 5. 
The subjects will be vaccinated as described in Section 6, with prime vaccinations administered 
at Day 1 for all groups, and boost vaccinations at Day 15 (Part 1 and Part 2, Group 2), or Day 29
(Part 2, Group 1) unless any of the pre-specified criteria not to proceed with vaccination are met 
(refer to Sections 6.2, 6.3 and 10.2 for details) or if a pause for vaccination of further subjects has 
been installed (see Section 9.3.2).
Prior to each vaccination, a urine pregnancy test (for female subjects of childbearing potential), a
targeted physical examination and measurements of vital signs will be performed and blood will 
be drawn for safety, immunogenicity and virologic (only for HIV-infected subjects) assessments. 
Refer to Sections 9.3, 9.4 and 9.5 for further details on the safety, immunogenicity and virologic
evaluations. 
Study vaccine will be prepared on-site by unblinded qualified study-site personnel not involved 
in any other study-related procedure who will place a blinding tape on the syringe to mask its 
content and send the vaccine to a blinded study vaccine administrator (see Definitions of Terms)
for administration to the subject (see Section 14.3 for details). Refer to Section 6 for further 
details on dosage and administration and post-vaccination monitoring.
All adverse events, serious adverse events, IREs and pregnancies will be collected and 
documented on the CRF, together with the information on any concomitant medications.

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Adherence to HAART will be assessed at every visit in HIV-infected subjects. For reporting of 
IREs, refer to Section 12.3.3.
Upon discharge from the site, subjects will be provided with a diary, a thermometer, and a ruler 
to measure and record local solicited adverse events and body temperature. Subjects will also 
record solicited local and systemic adverse events (reactogenicity) in the diary in the evening 
after vaccination and then daily for the next 7 days at approximately the same time each day. 
Diaries should be completed at home by the subject. For subjects having difficulty completing 
the diary independently, the sites will make arrangements to have the diary completed according 
to their local practice. Subjects will be instructed to contact the investigator immediately in case 
they experience an unsolicited adverse event (not listed on the diary card) or for any severe 
(grade 3) solicited adverse event (listed on the diary card). 
In all parts, subjects will come to the site at 7 days after each vaccination as indicated in the 
Time and Events Schedule. The subject’s diary will be reviewed by study-site personnel. The 
investigator will examine the injection site for occurrences of erythema, induration/swelling, 
pain/tenderness or itching at these visits in order to complete the relevant parts of the CRF. 
Blood samples will be taken for safety evaluations. In addition, vital signs will be assessed at the 
visits 7 days after the vaccination.
9.1.4.
Post-boost Follow-up
In all groups, subjects will come to the site at 21 and 42 days after the boost vaccination as 
indicated in the Time and Events Schedule. The investigator will examine the injection site for 
occurrences of erythema, induration/swelling, pain/tenderness or itching and will assess vital 
signs at these visits in order to complete the relevant parts of the CRF. 
All adverse events, serious adverse events, IREs and pregnancies will be collected and 
documented on the CRF during these visits, together with the information on any concomitant 
medications. Subjects will also have blood drawn for CD4+ cell count determination 
(HIV-infected subjects only) and immunogenicity and virologic (only for HIV-infected subjects) 
assessments at both visits as specified in the Time and Events Schedule. For reporting of IREs, 
refer to Section 12.3.3.
Subjects will be instructed to contact the investigator before the next visit (ie, on Day 195 or 
209) 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. 
When all subjects in a part have come to the site at 6 months after the boost vaccination, or 
discontinued earlier and the database for that part has been locked, that part will be unblinded. 
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 1-year post-boost visit (Part 1 and Part 2, Group 2: Day 380; Part 2, 
Group 1: Day 394) prior to unblinding will be required to attend the 1-year post-boost visit. All 
subjects who received Ad26.ZEBOV and MVA-BN-Filo will continue the study with a visit 
1 year after the boost vaccination. 

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Serious adverse event information and IREs will be collected until the end of the study.
Concomitant therapies should be recorded up to the 42-day post-boost visit and thereafter, 
concomitant therapies will be recorded only if given in conjunction with serious adverse events
and IREs. Pregnancies will be reported until the end of the study. Adherence to HAART will be 
assessed at every visit in HIV-infected subjects. Subjects' vital signs will be assessed, a physical 
examination will be performed and blood will be drawn for CD4+ cell count determination 
(HIV-infected subjects only), immunogenicity and virologic (only HIV-infected subjects) 
assessments as specified in the Time and Events Schedule at the 6-month post-boost visit and 
1-year post-boost visit (only for subjects on Ad26.ZEBOV and MVA-BN-Filo). Refer to 
Sections 9.3, 9.4 and 9.5 for further details on the CD4+ cell count determination, 
immunogenicity and virologic evaluations.
9.1.5.
VAC52150 Vaccine Development Roll-over Study
Female subjects in Part 2 who became pregnant with estimated conception within 28 days after 
vaccination with MVA-BN-Filo (or placebo) or within 3 months after vaccination with 
Ad26.ZEBOV (or placebo) and children born to vaccinated female subjects in Part 2 who 
became pregnant with estimated conception within 28 days after vaccination with MVA-BN-Filo 
(or placebo) or within 3 months after vaccination with Ad26.ZEBOV (or placebo) will be 
eligible for enrollment into the VAC52150EBL4001 Vaccine Development Roll-over study for 
long-term surveillance (for a total of up to 60 months after the prime vaccination). After 
unblinding, only female subjects and the children born to female subjects (with estimated 
conception within the period stated above) in Part 2 who received Ad26.ZEBOV and/or 
MVA-BN-Filo will be approached to consent for enrollment in the VAC52150 Vaccine 
Development Roll-over study for long-term surveillance. After unblinding, female subjects and 
the children born to female subjects (with estimated conception within the period stated above) 
in Part 2 who received placebo and had already been enrolled into the VAC52150 Vaccine 
Development Roll-over study will be discontinued from further participation in the roll-over 
study.
As of amendment 4 implementation, no subjects in Part 1 will be approached anymore in this 
study to roll-over to the VAC52150EBL4001 study.
9.2.
Endpoints
9.2.1.
Primary Endpoints
The primary endpoints are:

Safety as determined by:

Adverse events, collected until the 42-day post-boost visit.

Serious adverse events and IREs, collected until the end of the study.

Solicited local and systemic adverse events (reactogenicity), collected until 7 days after 
each vaccination.

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
Magnitude of humoral immune response against the EBOV GP by determining binding 
antibody levels using ELISA (in ELISA units/mL and/or endpoint-titers) until the 21-day 
post-boost visit.
9.2.2.
Secondary Endpoint
Comparison 
of
safety 
and 
tolerability 
of 
Ad26.ZEBOV/MVA-BN-Filo 
and 
MVA-BN-Filo/Ad26.ZEBOV regimens between healthy and HIV-infected adults. 
9.2.3.
Exploratory Endpoints
Additional exploratory analyses may be performed to further investigate study vaccine-elicited 
immune responses. The exploratory endpoints might include but are not limited to the following: 

Magnitude, kinetics and durability of humoral immune responses to EBOV GP, including 
neutralizing antibody response measured in titers that inhibit viral infection by a certain 
percentage (IC50, 80 or 90).

Magnitude, kinetics and durability of cellular immune responses for EBOV GP (EBOV GP 
specific T cell responses will be measured as the number of IFN-γ producing cells by 
ELISpot analysis).

Comparison between healthy and HIV-infected adults of the kinetics and durability of 
humoral and cellular immune responses to EBOV GP of Ad26.ZEBOV/MVA-BN-Filo and 
MVA-BN-Filo/Ad26.ZEBOV regimens.

Kinetics and durability of humoral immune responses, including the development of 
neutralizing antibodies, in healthy and HIV-infected adults for other filovirus GP (binding 
antibody response measured in ELISA units/mL and/or endpoint-titers; neutralizing 
antibody response measured as titers that inhibit viral infection by a certain percentage 
[IC50, 80 or 90]).

Kinetics and durability of cellular immune responses in healthy and HIV-infected adults for 
other filovirus GP (EBOV GP specific T cell responses will be measured as the number of 
IFN-γ producing cells by ELISpot analysis or the percentage of CD4+ or CD8+ T cells 
producing IFN-γ, tumor necrosis factor- α (TNF-α) and/or interleukin (IL)-2 by intracellular 
cytokine staining [ICS]).

Comparison of kinetics and durability of humoral and cellular immune responses to the 
other filovirus GP, of Ad26.ZEBOV/MVA-BN-Filo and MVA-BN-Filo/Ad26.ZEBOV
regimens between healthy and HIV-infected adults. 

Comparison of kinetics and durability of humoral and cellular immune responses to the 
EBOV
other 
filovirus
GP 
of 
Ad26.ZEBOV/MVA-BN-Filo 
and 
MVA-BN-Filo/Ad26.ZEBOV regimens between adults aged 18-50 and aged 51-70.

Frequency, magnitude, and durability of anti-vector responses in healthy and HIV-infected 
adults (measured by ELISA, virus neutralization assay [VNA] and/or plaque reduction 
neutralization test [PRNT].

Time course of CD4+ count in HIV-infected adults.

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
Changes in HIV RNA and HIV specific immune response (using HIV antigens in place of 
Ebola 
GP)
associated 
with 
vaccination
with
Ad26.ZEBOV/MVA-BN-Filo 
and 
MVA-BN-Filo/Ad26.ZEBOV regimens in HIV-infected adults.

Humoral immune responses in genital, rectal and oral secretions in a subset of healthy and 
HIV-infected adults for EBOV and other filovirus GP at selected sites.

Impact of host genetics on immune responses to the Ad26.ZEBOV/MVA-BN-Filo and 
MVA-BN-Filo/Ad26.ZEBOV prime-boost regimens in healthy and HIV-infected adults.

Immune 
epitope 
breadth
elicited 
by 
the 
Ad26.ZEBOV/MVA-BN-Filo 
and 
MVA-BN-Filo/Ad26.ZEBOV prime-boost regimens in healthy and HIV-infected adults.

Immunoglobulin subclass, glycosylation and effector functions of humoral responses to 
EBOV and other filovirus GP.

B 
cell, 
helper 
T 
cell, 
and 
cytotoxic 
T 
cell 
responses 
elicited 
by 
the 
Ad26.ZEBOV/MVA-BN-Filo and MVA-BN-Filo/Ad26.ZEBOV prime-boost regimens in 
healthy and HIV-infected adults.

Immune inflammatory responses elicited by the Ad26.ZEBOV/MVA-BN-Filo and 
MVA-BN-Filo/Ad26.ZEBOV regimens in healthy and HIV-infected adults on a multiplex 
array platform to evaluate cytokine and soluble factor responses to vaccination. 
9.3.
Safety Evaluations
9.3.1.
Safety Assessments
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 and IREs. Any clinically significant abnormalities 
(including those persisting at the end of the study/early withdrawal) will be followed by the 
investigator until resolution or until a clinically stable endpoint is reached (see Section 12). 
The investigators, together with the sponsor's study responsible physician, will be responsible for 
the safety monitoring of the study, and will halt vaccination of further subjects in case any of the 
pre-specified pausing rules described in Section 9.3.2 have been met or in case of other severe 
safety concerns. Further safety measures with regards to vaccination are described in 
Sections 6.2 and 6.3.
An IDMC will be appointed by the sponsor 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 collected at all visits from signing of 
the ICF onwards until 42 days post-boost. Thereafter, reporting will be limited to all serious 
adverse events and IREs up to the subject’s last study-related procedure. Solicited local and 

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systemic adverse events (reactogenicity, see below) will be reported by the subject until 7 days 
after each administration of study vaccine. Adverse events will be followed by the investigator as 
specified in Section 12.
Additional blood may be drawn to confirm and follow up on adverse events.
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 30 (±10) minutes after each 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). Any unsolicited, solicited local or systemic adverse 
events occurring while on site will be documented. Upon discharge from the site, subjects will 
receive a diary, a thermometer and a ruler to measure body temperature and solicited local 
reactions. Subjects will be instructed to record solicited local and systemic adverse events in the 
diary in the evening after each administration of study vaccine and then daily for the next 7 days 
(until Day 8) at approximately the same time each day to serve as a reminder to the subject for 
the next visit. On Day 8, the diary will be reviewed on site before the subject leaves the site. The 
investigator should discuss the information from the diary with the subject, document the relevant 
information in the clinic chart, and complete the relevant parts of the CRF as described in the 
CRF Completion Guidelines.
On-site and diary reported solicited adverse events will be captured on a separate CRF page as 
described in the CRF Completion Guidelines, in contrast to the unsolicited adverse events which 
will be reported on the Adverse Event page of the CRF. The investigator must record in the CRF 
his/her opinion concerning the relationship of the adverse event to study vaccine.
Solicited Local (Injection Site) Adverse Events
Subjects will also be instructed on how to note occurrences of erythema, induration/swelling 
(measured using the ruler supplied), pain/tenderness and itching at the injection site in the 
evening after each administration of study vaccine and then daily for the next 7 days in the diary
at approximately the same time each day. 
Solicited Systemic Adverse Events
Subjects will be instructed on how to record daily body temperature using a thermometer 
provided for home use. Subjects should record the body temperature in the evening after each 
vaccination and then daily for the next 7 days in the diary at approximately the same time each 
day. If >1 measurement is made on any given day, the highest value will be recorded in the CRF. 

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Subjects will also be instructed on how to note the following symptoms in the evening after each 
administration of study vaccine and then daily for the next 7 days in the diary at approximately 
the same time each day: 

Nausea/vomiting

Arthralgia

Fever

Headache

Fatigue/malaise

Myalgia

Chills
If a solicited local or systemic adverse event is not resolved at Day 8, the follow-up will be 
captured on the diary. The subject will be instructed to record the date of last symptoms and 
maximum severity in the diary after resolution.
Suspected Cardiac Events
In case of a cardiac event, an ECG will be obtained and the subject will undergo cardiac enzyme 
testing and/or be referred to a local cardiologist as clinically indicated.
Clinical Laboratory Tests 
Blood samples for serum chemistry and hematology, and for other tests (see below) and a urine 
sample for urinalysis will be collected at the time points indicated in the Time and 
Events Schedule. The investigator must review the laboratory results, document this review, and 
record any clinically relevant changes occurring during the study in the Adverse Event section of 
the CRF up to the 42-day post-boost visit. Thereafter, only serious adverse events and IREs need 
to be recorded. The laboratory reports must be filed with the source documents. For reporting of 
IREs, refer to Section 12.3.3.
Approximate blood volume expected to be drawn per visit for clinical laboratory assessments: 

13 mL at screening

7 mL at other visits
Note: for HIV-infected subjects, an additional 4 mL will be taken for monitoring of 
CD4+ cell count at time points indicated in the Time and Events Schedule. 
The following tests will be performed by the local laboratory, unless otherwise specified:

Hematology Panel 

hemoglobin

hematocrit

red blood cell count

white blood cell count with differential

platelet count

Serum Chemistry Panel 

alanine aminotransferase 

creatinine

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
Urinalysis – Dipstick

specific gravity

pH

glucose

protein

blood

ketones
In case of positive urinalysis dipstick results for >1+ protein or blood, the sediment will be 
examined microscopically (only red blood cells (RBC) will be documented).
Additional clinical laboratory assessments to be performed are as follows:
Urine pregnancy test for female subjects of childbearing potential at screening and prior to 
each study vaccination.
CD4+ cell count for HIV-infected subjects at screening, on Day 1, on the day of the boost 
vaccination, at 21 and 42 days after the boost vaccination and at 6 months and 1 year after the 
boost vaccination.
Serology: HIV type 1 or HIV type 1/2 at screening.
Laboratory abnormalities will be determined according to the Toxicity Table for Use in Trials 
Enrolling Healthy Adults (Attachment 2).
Electrocardiogram
A single, 12-lead ECG will be performed at screening for subjects >50 years 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 for at least 5 minutes before ECG collection 
and should refrain from talking or moving arms or legs.
Vital Signs (blood pressure, pulse/heart rate, body temperature)
Vital sign measurements will be performed at the time points indicated in the Time and 
Events Schedule. Blood pressure and pulse/heart rate measurements will be assessed (at rest) 
with a completely automated device. Manual techniques will be used only if an automated device 
is not available. Confirmatory measurements can be performed if inconsistent with a prior 
measurement.
Either oral or axillary body temperatures may be measured and the site of measurement must be 
captured in the CRF. 

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Physical Examination 
A full physical examination including height and body weight will be performed at screening. 
Calculation of the body mass index (BMI), will be recorded in the CRF. At other visits, an 
abbreviated, symptom-directed physical examination will be performed as indicated based on 
any clinically relevant issues, clinically relevant symptoms and medical history. The symptom-
directed physical examination may be repeated if deemed necessary by the investigator. Physical 
examinations will be performed by the investigator or by a designated medically-trained 
clinician. 
A full physical examination includes the following: general appearance, eyes, ears, nose, throat, 
cardiovascular system, respiratory system, gastrointestinal system, and skin and mucous 
membranes. A genitourinary exam is not required. A neurological and musculoskeletal 
examination as well as an examination of the lymph nodes will also be performed. An
abbreviated, symptom-directed physical examination includes examination of the injection 
site(s), heart, lungs and abdomen.
The height should be measured at the screening visit. To obtain the actual body weight, subjects 
should be weighed without bulky outer clothing.
9.3.2.
Pausing Rules
The investigators and the sponsor's study responsible physician will review the safety of enrolled 
subjects on an ongoing basis. The sponsor's study responsible physician will be involved in all 
discussions and decisions.
If any of the following events occur in any subject in any part who received at least 1 dose of 
study vaccine in the study (at any site), the site investigator will halt the vaccination of further 
subjects and the sponsor's study responsible physician will be notified immediately. The 
sponsor's study responsible physician will inform all the other investigators to halt further 
vaccination as well.

Death in any subject, considered at least possibly related to the study vaccine OR

An anaphylactic reaction within 24 hours of vaccination or the presence of generalized 
urticaria within 72 hours of vaccination in any subject, considered at least possibly related to 
the study vaccine OR

A life-threatening or other serious adverse event in any subject, considered at least possibly 
related to the study vaccine
If any of the following events occur in any subject who received at least 1 dose of study vaccine 
in the study (across all sites), the sponsor's study responsible physician will notify all 
investigators to halt vaccination of further subjects:

Three or more subjects experience a severe (grade 3) (non-serious) unsolicited 
adverse event (of the same type) considered to be related to any of the study vaccines that 
persists for 3 or more days OR

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
Three or more subjects experience a persistent (upon repeat testing) severe (grade 3) 
(non-serious) abnormality related to the same laboratory parameter and considered to be 
related to any of the study vaccines OR

Three or more subjects experience the same severe (grade 3) (non-serious) solicited 
systemic reaction considered to be related to any of the study vaccines that persists for 3 or 
more days (subjective systemic reaction corroborated by study personnel).
In case of occurrence of any of the events described above, the sponsor's study responsible 
physician will notify the IDMC immediately. Dosing will be halted and all applicable health 
authorities will be notified. Within 3 business days, the IDMC will convene to review the 
available safety data as outlined in the charter and to discuss study suspension or discontinuation 
of further vaccination or to decide that vaccination may resume. The sites will be allowed to 
resume activities upon receipt of a written notification from the sponsor. The criteria for pausing 
will be re-set each time and the same criteria have to be met again to halt further vaccination. 
The communications from the IDMC will be forwarded by the investigator to the Independent 
Ethics Committee/ Institutional Review Board (IEC/IRB) according to local standards and 
regulations and by the sponsor to relevant health authorities.
9.4.
Immunogenicity Evaluations
Venous blood samples will be collected for the determination of immune responses at the time 
points indicated in the Time and Events Schedule. Samples for assessment of humoral and 
cellular immune responses will be taken from all subjects; a list of assessments can be found in 
Table 3. At selected sites, genital, rectal and oral secretions will be taken for assessment in a 
subset of subjects of humoral immune responses for EBOV, SUDV and MARV GP, dependent 
on assay availability.
Sample collection and processing will be performed by the study-site personnel according to 
current versions of approved standard operating procedures. The laboratory manual contains 
further details regarding the collection, handling, labeling, and shipment of blood samples and 
secretions to the respective laboratories.
Approximate blood volume expected to be drawn per visit for immunogenicity evaluations:

96 mL 
The immunologic assessments and purposes are summarized in Table 3. The exploratory assay 
package may include, but might not be limited to, the listed assays.

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Table 3:
Summary of Immunologic Assessments in Serum and PBMC
Sample
Purpose (non-exhaustive)
Serum
- Analysis of antibodies binding to EBOV GP, possibly using different EBOV GPs and/or other 
filovirus GP (ELISA)
- Analysis of neutralizing antibodies to EBOV GP, possibly using different EBOV GPs and/or 
other filovirus GP (VNA)
- Analysis of binding and/or neutralizing antibodies to adenovirus and/or MVA (ELISA and/or 
neutralization test)
- Analysis of anti-EBOV GP, or other filovirus GP antibody characteristics and functionality, 
including IgG subtyping (molecular antibody characterization )
- In HIV-infected subjects, analysis of antibodies to HIV antigens (ELISA and/or neutralization 
assays)
PBMC
- Analysis of T cell IFN-γ responses to EBOV GP and possibly other filovirus GP (ELISpot) 
- Analysis of T cell responses to EBOV GP, and/or other filovirus GP (including CD4/8, IL-2, 
IFN-γ, TNF-α and/or activation markers) (ICS)
- In HIV-infected subjects: analysis of T cell IFN-γ responses to HIV antigens (ELISpot)
- In HIV-infected subjects: analysis of T cell responses to HIV antigens (including CD4/8, IL-2, 
IFN-γ, TNF-α and/or activation markers) (ICS)
IgG: immunoglobulin G; ICS: intracellular cytokine staining; IFN-γ: interferon-γ; IL: interleukin; TNF: tumor 
necrosis factor; VNA: virus neutralization assay
9.5.
Virologic Evaluations
Venous blood samples will be collected from HIV-infected subjects for the determination of HIV 
viral load (assayed by RNA polymerase chain reaction [PCR]) at the time points indicated in the 
Time and Events Schedule. Viral sequencing may be performed on these samples if the HIV 
viral load is sufficiently high. 
In addition, stored serum or plasma of HIV-infected subjects may be used to assess antiretroviral 
drug levels.
Sample collection and processing will be performed by the study-site personnel according to 
current versions of approved standard operating procedures. The laboratory manual contains 
further details regarding the collection, handling, labeling, and shipment of blood samples to the 
respective laboratories.
Approximate blood volume expected to be drawn per visit for viral load determination and 
sequencing:

6 mL at screening, 4 mL at other visits
9.6.
Pharmacogenomic (DNA) Evaluations
DNA samples will be analyzed for human leukocyte antigen (HLA) type determination (where 
local regulations permit) to explore the impact of host genetics on immune responses to the 
Ad26.ZEBOV/MVA-BN-Filo and MVA-BN-Filo/Ad26.ZEBOV prime-boost regimens. No 
additional venous blood samples need to be collected for this evaluation, samples collected on 
the day of the prime vaccination will be used. Subject participation in the pharmacogenomic 
research is optional and will require additional consent.

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9.7.
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 within 8 weeks before Day 1 or plan to donate blood until 
42-days post-boost (see Section 4.2.1). 
Subjects will be provided with a letter describing the study if requested by the subject. Subjects 
participating in the study will be provided with a "site information card" and instructed to carry 
this card with them for the duration of the study (see Section 12.3.1).
9.8.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the CRF or laboratory 
requisition form.
Refer to the Time and Events Schedule for the timing and frequency of all sample collections.
Instructions for the collection, handling, storage, and shipment of samples are found in the 
laboratory manual that will be provided. Collection, handling, storage, and shipment of samples 
must be under the specified, and where applicable, controlled temperature conditions as indicated 
in the laboratory manual.
9.9.
Optional Procedures
Subjects will have the option of participating in separately consented collections and procedures 
in addition to the main protocol procedures as detailed below. Participation of sites in these 
collection and procedures varies across sites, and is detailed in each site-specific addendum. If 
any of the procedures provides evidence of an abnormal finding, the participant will be referred 
for diagnosis and care. Specifics on referral are provided in the site-specific addendum.
9.9.1.
Apheresis for Part 1 Subjects
Up to 20 subjects (10 HIV-infected, 10 healthy) from Part 1 will be enrolled for optional 
apheresis for collection of PBMC and plasma on the Day 36 and Day 57 visits, given they have 
provided specific consent for this procedure. Up to a total of 10 Part 1 subjects (irrespective of 
HIV status) with robust immune responses post-boost may also be enrolled for an optional 
apheresis procedure performed after unblinding at a predefined visits or at an unscheduled visit
for better characterization of immune responses. PBMCs and plasma will be obtained using 
automated apheresis techniques conducted by a qualified apheresis nurse/technician. 
Approximately 25 mL of red blood cell volume will be lost as residual loss in the machine 
during the procedure.

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9.9.2.
Mucosal Secretions for Part 2 Subjects
Collection of genital, rectal and oral secretion samples will be offered at Part 2 sites (Kenya, 
Tanzania, and Uganda) at time points indicated in the Time and Events Schedule.
9.9.2.1.
Collection of Genital and Rectal Secretion Samples
Female Subjects
Consenting women will be instructed on how to use a Softcup device to collect cervical and 
vaginal secretions. The cup will remain in place for 4-12 hours. Pregnant women and those with 
a history of toxic shock syndrome will be excluded. Date of last menstrual period will be 
recorded at each collection visit. Collection will not take place if the woman is menstruating or 
has symptoms of active inflammation or infection of the vagina or cervix. Rectal sponge 
secretions will also be collected however, will be deferred if there are signs or symptoms of 
perianal inflammation. Subjects may participate in cervicovaginal secretion collection if they 
choose to defer rectal sponge secretion collections.
Male Subjects
Consenting men will be asked to ejaculate into a sterile container for semen collection. Rectal 
sponge secretions will also be collected. Semen and rectal sponge collections will be deferred 
from men if there are signs or symptoms of urethral or perianal inflammation, respectively. 
Subjects may participate in semen collection if they choose to defer rectal sponge secretion 
collections.
9.9.2.2.
Collection of Oral Secretion Samples
Consenting men and women will be instructed to provide oral secretion samples by 
expectorating into a cup.
10.
SUBJECT COMPLETION/DISCONTINUATION OF STUDY 
VACCINE/WITHDRAWAL FROM THE STUDY
10.1.
Completion
A subject will be considered to have completed the study if he or she has completed all 
assessments at the 6-month post-boost visit for subjects who received placebo or at the 1-year 
post-boost visit for subjects who received Ad26.ZEBOV and MVA-BN-Filo. 
10.2.
Discontinuation of Study Vaccine/Withdrawal From the Study
Discontinuation of Study Vaccine
If a subject's study vaccine must be discontinued before the end of the vaccination schedule, this 
will not result in automatic withdrawal of the subject from the study.
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.

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A subject's study vaccine should be permanently discontinued if:

The investigator believes that for safety reasons (eg, adverse event) it is in the best interest 
of the subject to discontinue study vaccine

The subject becomes pregnant

The subject has confirmed Ebola virus disease through natural exposure to the virus (eg, by 
travel to an affected country)

The subject experiences any of the events described in Section 6.3

The randomization code is broken by the investigator or the study-site personnel
Subjects meeting any of the reasons listed above must not receive any further study vaccine, but 
should continue to be monitored for safety and for immunogenicity according to the protocol if 
this does not result in safety risks for the subject. In case of early discontinuation of study 
vaccine due to an adverse event, the investigator will collect all information relevant to the 
adverse event and safety of the subject, and will follow the subject to resolution, or until reaching 
a clinically stable endpoint. 
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. The measures taken to follow up must be documented.
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

Receipt of blood products or immunoglobulin during the study.
If a subject withdraws early from the study for any of the reasons listed above (except in case of 
death), early withdrawal assessments (ie, physical examination, vital signs, CD4+ cell count [as 
applicable], [serious] adverse events and concomitant medications review, immunogenicity, and 
virologic assessments) should be obtained. 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. 

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When a subject withdraws before completing the study, the reason for withdrawal is to be 
documented in the CRF and in the source document. Study vaccine assigned to the withdrawn 
subject may not be assigned to another subject. For subjects who withdraw from the study after 
randomization but before the prime vaccination, an additional subject will be enrolled who will 
receive the same vaccination regimen as the withdrawn subject. No additional subject will be 
enrolled in case a subject withdraws from the study after receiving the prime vaccination.
10.3.
Withdrawal From the Use of Research Samples
A subject who withdraws from the study will have the following options for storage of samples 
for potential future use:

The collected samples will be retained and used in accordance with the subject's original 
informed consent for storage of samples for future use.

The subject may withdraw consent for storage of samples for potential future use (see 
Section 16.2.6), in which case the samples will be destroyed and no further testing will take 
place. To initiate the sample destruction process, the investigator must notify the sponsor 
study site contact of withdrawal of consent for the storage of leftover samples for future 
research and request sample destruction. The sponsor study site contact will, in turn, contact 
the biomarker representative to execute sample destruction. If requested, the investigator 
will receive written confirmation from the sponsor that the samples have been destroyed.
Details of the sample retention for research are presented in the ICF.
11.
STATISTICAL METHODS
Statistical analysis will be done by the sponsor or under the authority of the sponsor. A general 
description of the analytic approach for the safety and immunogenicity data is outlined below. 
Specific details on methods will be provided in the Statistical Analysis Plan (SAP). 
Interim analyses may be performed as described in Section 11.6.
The final analysis will be performed when all subjects have completed the last study-related visit 
or discontinued earlier.
A general description of the statistical methods to be used to analyze the safety and 
immunogenicity data is outlined below. 
11.1.
Sample Size Determination
An overall planned sample size of 575 subjects includes 460 subjects who will receive active 
prime-boost vaccination to substantially contribute to an overall safety database of the 
Ad26.ZEBOV and MVA-BN-Filo prime-boost regimen.
In Part 1, a total of 60 subjects (40 healthy and 20 HIV-infected) are planned to be vaccinated 
with MVA-BN-Filo prime vaccination followed by Ad26.ZEBOV 14 days later.
In Part 2, Group 1, a total of 320 subjects (160 healthy and 160 HIV-infected) will be vaccinated 
with Ad26.ZEBOV on Day 1, followed by MVA-BN-Filo 28 days later and in Group 2, a total of 

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80 subjects (40 healthy and 40 HIV-infected) will be given MVA-BN-Filo prime vaccination 
followed by Ad26.ZEBOV 14 days later.
The sample size is based on the probability of observing an adverse event given the true 
underlying incidence and is described in Table 4. 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 16.8%, 8.8%, 6.0%, 4.5%, 2.3%, 1.5%, 1.1%, and 0.8% for a total of 20, 40, 
60, 80, 160, 240, 320, and 460 subjects on Ad26.ZEBOV and MVA-BN-Filo, respectively. Note 
that this does include some scenarios based on combining the data from Part 1 and Part 2. An 
analysis that combines data from Part 1 and Part 2 is appropriate for estimating safety parameters
although any formal comparisons between vaccination regimens or HIV cohorts would likely 
only consider data from Part 2 of the study.
Table 4:
Probability of Observing at Least One Adverse Event Given a True Adverse Event Incidence
True Adverse Event Incidence
N=20
N=40
N=60
N=80
N=160
N=240
N=320
N=460
0.1%
2.0%
3.9%
5.8%
7.7%
14.8%
21.4%
27.4%
36.9%
0.5%
9.5%
18.2%
26.0%
33.0%
55.2%
70.0
79.9%
90.0%
1%
18.2%
33.1%
45.3%
55.3%
80.0
91.0%
96.0%
99.0%
2.5%
39.7%
63.7%
78.1%
86.8%
98.3%
99.8%
100%
100%
5%
64.2%
87.2%
95.4%
98.4%
100%
100%
100%
100%
10%
87.8%
98.5%
99.8%
100%
100%
100%
100%
100%
Table 5 below shows the detectable differences for a 2-sided 5% level t-test with 90% power for 
comparing immune response (ELISA antibody levels against EBOV GP) at Day 42 post-boost. 
The 4 scenarios provided focus on the likely comparisons of interest (healthy versus
HIV-infected within each vaccination regimen, across vaccination regimens regardless of HIV 
status, and HIV status exclusive of vaccination regimen). 
Table 5:
Magnitude of Pairwise Difference to be Detected Between Vaccine Regimens for a Given 
Sample Size 
Variability ELISA antibody
levels (SD, log10 scale)
Detectable difference, log10 scale *
n1=160,
n2=40
n1=320,
n2=80
n1=160,
n2=160
n1=40,
n2=40
0.3
0.18
0.12
0.11
0.22
0.4
0.23
0.16
0.15
0.29
0.5
0.29
0.2
0.18
0.37
SD: standard deviation
* 90% power, 5% significant level for 2-sided hypothesis
As the study has adequate power to detect differences in active vaccination regimens, the study 
will also likely be suitably powered to detect differences between active and placebo subjects.

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11.2.
Analysis Sets
The Full Analysis set includes all subjects who were randomized and received at least 1 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 1 post-vaccination immunogenicity blood draw.
The Per Protocol Analysis set includes all randomized and vaccinated subjects, who received 
both the prime and boost vaccinations (administered not more than 10 days outside the visit 
window), have immunogenicity data from baseline and at least 1 post-vaccination evaluable 
immunogenicity sample, and have no major protocol violations influencing the immune 
response.
11.3.
Subject Information
For all subjects, demographic characteristics (eg, age, height, weight, BMI, race, and sex) and 
screening/baseline characteristics (eg, physical examination, medical history) will be tabulated 
and summarized with descriptive statistics.
11.4.
Safety Analyses
The primary safety endpoint in Part 1 and Part 2 are Adverse events, collected until the 42-day 
post-boost visit, serious adverse events and IREs, collected until the end of the study and 
solicited local and systemic adverse events (reactogenicity), collected until 7 days after each 
vaccination. Safety analyses will be conducted during the planned interim analyses, primary 
analysis and final analysis. In addition, safety analyses may be conducted during ad hoc interim 
analyses. For more details about the interim and final analyses, see Sections 11 and 11.6. 
Safety data will be analyzed descriptively (including 95% confidence intervals, if applicable). In 
general, the primary safety plan will analyze each part separately and secondarily analyze the 
combined safety data from Part 1 with Part 2, Group 2 (MVA prime/Ad26 boost 0, 14-day 
regimen). In detail, safety data will be separately described by part, HIV infection status, and 
vaccination regimen (in Part 2 only). For purposes of estimating rates and confidence intervals,
various combinations of those factors will be considered (including collapsing across parts for 
analyzing the adverse event profile of the MVA/Ad26 regimen).
Baseline for all safety parameters will be defined as the last value before the prime vaccination.
Exploratory statistical analyses may be considered comparing safety endpoints (such as 
proportion of subjects experiencing systemic reactogenicity) between active and placebo subjects 
within part, group and cohort or across groups and cohorts among active subjects (eg, comparing 
rates between healthy and HIV-infected subjects with a similar vaccination regimen). Such 
comparisons will be described in the SAP and will be considered exploratory as the study is not 
definitively powered to detect small differences in safety rates between vaccination regimens or 
infection status or formally prove equivalence between regimens. Instead the purpose of such a 

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comparison would be to identify any potential safety issue which could then be formally assessed 
for equivalence in a future study or considered in a meta-analysis combining data across multiple 
studies.
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 
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 and/or subject narratives 
may be provided as appropriate, for those subjects who die, discontinue study vaccinations due 
to an adverse event, or experience a severe or serious adverse event. The analysis for solicited 
adverse events will be done on those subjects in the Full Analysis set for whom reactogenicity 
assessments are available in the database. The analysis of unsolicited adverse events will be done 
based on the Full Analysis set. 
Physical Examination
Physical examination abnormalities will be listed. BMI will be calculated using the recording of 
height at screening. 
Vital signs 
Vital signs abnormalities will be tabulated by worst abnormality grade.
Clinical Laboratory Tests
Laboratory abnormalities will be determined in accordance with Toxicity Table for Use in Trials 
Enrolling Healthy Adults (Attachment 2). Laboratory abnormalities will be tabulated per 
treatment group by worst abnormality grade.
11.5.
Immunogenicity Analyses
The primary immunogenicity endpoint in Part 1 and Part 2 is the Day 21 post-boost visit. 
Immunogenicity analyses will be conducted during the planned interim analyses and the final 
analysis. In addition, immunogenicity analyses may be conducted during ad hoc interim 
analyses. For more details about the interim and final analyses, see Sections 11 and 11.6. Within 
each part, the HIV-infected groups will be analyzed separately and in comparison with the 
healthy groups.
Descriptive statistics (actual values and changes from baseline, including 95% confidence 
intervals, if applicable) will be calculated for continuous immunologic parameters by time point. 
Graphical representations of changes in immunologic parameters will be prepared, as applicable. 
Frequency tabulations will be calculated for discrete (qualitative) immunologic parameters by 
time point. Response patterns over time for the immunologic parameters will be analyzed, taking 
into account within-subject correlations, to describe differences between the vaccination 
schedules at 21 days post-boost, 42 days post-boost, 6 months post-boost and 1 year post-boost.

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Immunogenicity endpoints will be compared between treatment groups, in particular ELISA 
levels for Part 2. Immunogenicity data will be compared between vaccine groups for healthy and 
HIV-infected groups separately and combined. The immunogenicity data will also be compared 
between the healthy and HIV-infected groups within each vaccination group and across 
vaccination groups.
Details on the statistical analysis of the immunogenicity data will be provided in the SAP.
11.6.
Interim Analyses
An interim analysis will be conducted when all subjects in Part 1 have completed the 21-day 
post-boost visit, or discontinued earlier. The purpose of this interim analysis is to evaluate the 
effect of vaccination on the HIV viral load of HIV-infected subjects from a safety perspective. 
This interim analysis will be reviewed by the PSRT and forwarded to the IDMC for review. An 
additional interim analysis will be done when all subjects in Part 1 have completed the 1-year
post-boost visit or discontinued earlier.
Additional (ad hoc) interim analyses may be performed during the study 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 unless a significant safety concern has been identified.
A separate interim SAP will be prepared before the conduct of an interim analysis.
11.7.
Independent Data Monitoring Committee
An IDMC will be established to monitor data on an ongoing basis to ensure the continuing safety 
of the 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 PSRT (see 
Section 11.8) before the start of the study. The IDMC will consist of at least 1 medical expert in 
the relevant therapeutic area and at least 1 statistician. The IDMC responsibilities, authorities, 
and procedures will be documented in its charter. Any safety reports/interim data from the parts
in this study reviewed by the IDMC and the recommendations of the IDMC will be shared with 
the local health authorities and the IECs/IRBs.
11.8.
Protocol Safety Review Team and Protocol Safety Review Team Reviews
The PSRT will review all adverse events (including reportable adverse events) on a regular and 
expedited basis as needed. In addition, the PSRT will review aggregate safety data reports from 
all sites on a regular basis as dictated by study progress. This team includes the following: Study 
Chair, site principal investigators (PIs), all Department of Defense (DoD) Research Monitors 
from each participating site, and the sponsor’s study physician or their designees. Additional 

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participants could include but is not limited to associate investigators and senior clinical research 
nursing staff. A quorum is established with the Protocol Chair, 4 of 7 site PIs and the sponsor’s 
study physician or their designee.
The PSRT will review summaries for the IDMC and make clarifications for the IDMC as 
needed.
12.
ADVERSE EVENT REPORTING
Timely, accurate, and complete reporting and analysis of safety information from clinical studies 
are crucial for the protection of subjects, investigators, and the sponsor, and are mandated by 
regulatory agencies worldwide. The sponsor has established Standard Operating Procedures in 
conformity with regulatory requirements worldwide to ensure appropriate reporting of safety 
information; all clinical studies conducted by the sponsor or its affiliates will be conducted in 
accordance with those procedures.
12.1.
Definitions
12.1.1.
Adverse Event Definitions and Classifications
Adverse Event
An adverse event is any untoward medical occurrence in a clinical study subject administered a 
medicinal (investigational or non-investigational) product. An adverse event does not necessarily 
have a causal relationship with the treatment. An adverse event can therefore be any unfavorable 
and unintended sign (including an abnormal finding), symptom, or disease temporally associated 
with the use of a medicinal (investigational or non-investigational) product, whether or not 
related to that medicinal (investigational or non-investigational) product. (Definition per 
International Council for Harmonisation [ICH]).
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

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
Is a congenital anomaly/birth defect

Is a suspected transmission of any infectious agent via a medicinal product

Is Medically Important*
*Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
also appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the subject 
or may require intervention to prevent one of the other outcomes listed in the definition above. 
These should usually be considered serious.
If a serious and unexpected adverse event occurs for which there is evidence suggesting a causal 
relationship between the study vaccine and the event (eg, death from anaphylaxis), the event 
must be reported as a suspected unexpected serious adverse reaction (SUSAR) (even after the 
study is over, if the sponsor, IDMC or investigator becomes aware of them) by the sponsor to the 
applicable health authorities and by the investigator to the IEC/IRB according to regulatory and 
local requirements. 
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An adverse event is considered unlisted if the nature or severity is not consistent with the 
applicable product reference safety information. For Ad26.ZEBOV and MVA-BN-Filo, the 
expectedness of an adverse event will be determined by whether or not it is listed in the 
Investigator's Brochures and Addenda, if applicable.11,12
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

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
Isolated paresthesia of >7 days duration
Symptoms, signs or conditions which might (or might not) represent the above diagnoses, should 
be recorded and reported as IREs even if the final or definitive diagnosis has not yet been 
determined, and alternative diagnoses have not yet been eliminated or shown to be less likely. 
Follow up information and final diagnoses, if applicable, should be submitted as soon as they 
become available.
If the IRE is also serious (serious adverse event), it will be reported using the same process as for 
other serious adverse events.
Note: IREs are to be reported from the signing of the ICF onwards until the end of the study.
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.
An adverse event is considered not associated with the use of the study vaccine if the attribution 
is not related or doubtful by the definitions listed in Section 12.1.2, Attribution Definitions.
12.1.2.
Attribution Definitions
Every effort should be made by the investigator to explain any adverse event and to assess its 
potential causal relationship, ie, to administration of the study vaccine or to alternative causes,
eg, natural history of underlying disease(s), concomitant drug(s). This applies to all adverse 
events, whether serious or non-serious. Assessment of causality must be done by a licensed study 
physician (the investigator or designee).
The investigator will use the following guidelines to assess the causal relationship of an adverse 
event to study vaccine:
Not Related
An adverse event that is not related to the use of the vaccine.
Doubtful
An adverse event for which an alternative explanation is more likely, eg, concomitant drug(s), 
concomitant disease(s), or the relationship in time suggests that a causal relationship is unlikely.
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.

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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.
12.1.3.
Severity Criteria 
Adverse events and laboratory data will be coded for severity using the toxicity grading tables in
Attachment 2. 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 tables above. 
12.2.
Special Reporting Situations
Safety events of interest on a sponsor study vaccine that may require expedited reporting or 
safety evaluation include, but are not limited to:

Administration of an overdose of study vaccine 

Accidental or occupational exposure to a study vaccine

Administration error involving a study vaccine (with or without subject/patient exposure to 
the study vaccine, eg, name confusion)

IREs
Special reporting situations should be recorded in the CRF. For reporting of IREs, refer to 
Section 12.3.3. Any special reporting situation that meets the criteria of a serious adverse event
should be recorded on the Serious Adverse Event page of the CRF.
12.3.
Procedures
12.3.1.
All Adverse Events
All adverse events and special reporting situations, whether serious or non-serious, will be 
reported from the time a signed and dated ICF is obtained until 42 days post-boost, and serious 

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adverse events and IREs will be collected from signing of the ICF onwards until the end of the 
study. Subjects will be instructed to record solicited local and systemic adverse events
(reactogenicity) in the diary in the evening after each vaccination and then daily for the next 
7 days at approximately the same time each day.
Serious adverse events must be reported by the investigator using the Serious Adverse Event 
Form. SUSARs will be reported even after the study is over, if the sponsor, the IDMC or the 
investigator becomes aware of them. The sponsor will evaluate any safety information that is 
spontaneously reported by an investigator beyond the time frame specified in the protocol.
The investigator will monitor and analyze the study data including all adverse events and clinical 
laboratory data as they become available and will make determinations regarding the severity of 
the adverse experiences and their relation to study vaccine. All adverse events will be deemed 
related to study vaccine or not related to study vaccine, according to the terminology used in 
Section 12.1.2. To ensure that all adverse events are captured in a timely manner, the CRF will 
be entered in real-time and subjected to review to identify adverse events which may invoke 
pausing rules.
The investigator must review both post-injection reactogenicity and other adverse event CRF to 
insure the prompt and complete identification of all events that require expedited reporting as 
serious adverse events, invoke pausing rules or are other serious and unexpected events.
All adverse events, regardless of seriousness, severity, or presumed relationship to study vaccine, 
must be recorded using medical terminology in the source document and the CRF. Whenever 
possible, diagnoses should be given when signs and symptoms are due to a common etiology 
(eg, cough, runny nose, sneezing, sore throat, and head congestion should be reported as "upper 
respiratory infection"). Investigators must record in the CRF their opinion concerning the 
relationship of the adverse event to 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. 
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

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
Statement, in the local language(s), that the subject is participating in a clinical study and 
that results from Ebola virus serological screening tests should be interpreted with caution as 
the subject could have a false positive test (not truly infected with EBOV) as a result of an 
immune response to the candidate Ebola vaccine.

Investigator's name and 24-hour contact telephone number

Local sponsor's representative (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
12.3.2.
Serious Adverse Events
All serious adverse events occurring during the study must be reported to the appropriate sponsor 
contact person by study-site personnel within 24 hours of their knowledge of the event.
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:

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).

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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.
12.3.3.
Immediate Reportable Events
One subject in the study VAC52150EBL2001 experienced a serious and very rare condition 
called “Miller Fisher syndrome”. This condition consists of double vision, pain on moving the 
eye, and difficulty with balance while walking. Miller Fisher syndrome most commonly occurs 
following a recent infection. The subject experienced these symptoms about a week after 
suffering from a common cold and fever. The event happened about a month after boost 
vaccination with either MVA-BN-Filo or placebo. This subject had to go to the hospital for 
treatment and has recovered. After an extensive investigation, the event has been considered to 
be doubtfully related to vaccine and most likely related to the previous common cold.
Any events of neuroimmunologic significance (listed in Section 12.1.1) should be categorized as 
IREs and should be reported throughout the study (from signing of the ICF onwards until the end 
of 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.
In addition, all serious adverse events that are considered related or possibly related, and all 
deaths, will be promptly (within 48 hours) reported to the WRAIR IRB and local IRB.
The principal investigator will then submit written reports within 10 working days to the WRAIR 
IRB. Follow-up reports will be submitted as additional information becomes available. A 
summary of the non-serious adverse events and serious adverse events (both related and 
unrelated) that occurred during the reporting period will be included in the continuing review 
report to the WRAIR IRB.
12.3.4.
Pregnancy
Pregnancies will be reported from signing of the ICF until the end of the study.
All initial reports of pregnancy in female subjects or partners of male subjects must be reported 
to the sponsor by the study-site personnel within 24 hours of their knowledge of the event using 
the appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg, spontaneous 
abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are considered serious 
adverse events and must be reported using the Serious Adverse Event Form. Any subject who 

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becomes pregnant during the study must be promptly withdrawn from further study vaccination 
but should continue participation in the study for safety follow-up.
Because the effect of the study vaccine on sperm is unknown, pregnancies in partners of male 
subjects included in the study will be reported as noted above.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required to be sent to the sponsor.
The parent(s)/legal guardian of children born to vaccinated female subjects in Part 2 who become 
pregnant with estimated conception within 28 days after vaccination with MVA-BN-Filo (or 
placebo) or within 3 months after vaccination with Ad26.ZEBOV (or placebo), will also be 
approached to consent for enrollment of their offspring into the VAC52150EBL4001 Vaccine 
Development Roll-over study (see Section 9.1.5).
12.4.
Contacting Sponsor Regarding Safety
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding safety issues or questions regarding the study are listed in the Contact Information 
page(s), which will be provided as a separate document.
13.
PRODUCT QUALITY COMPLAINT HANDLING
A product quality complaint (PQC) is defined as any suspicion of a product defect related to 
manufacturing, labeling, or packaging, ie, any dissatisfaction relative to the identity, quality, 
durability, or reliability of a product, including its labeling or package integrity. A PQC may have 
an impact on the safety and efficacy of the product. Timely, accurate, and complete reporting and 
analysis of PQC information from studies are crucial for the protection of subjects, investigators, 
and the sponsor, and are mandated by regulatory agencies worldwide. The sponsor has 
established procedures in conformity with regulatory requirements worldwide to ensure 
appropriate reporting of PQC information; all studies conducted by the sponsor or its affiliates 
will be conducted in accordance with those procedures.
13.1.
Procedures
All initial PQCs must be reported to the sponsor by the study-site personnel within 24 hours after 
being made aware of the event.
If the defect is combined with a serious adverse event, the study-site personnel must report the 
PQC to the sponsor according to the serious adverse event reporting timelines (refer to 
Section 12.3.2). A sample of the suspected product should be maintained for further investigation 
if requested by the sponsor.
13.2.
Contacting Sponsor Regarding Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding product quality issues are listed in the Contact Information page(s), which will be 
provided as a separate document.

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14.
STUDY VACCINE INFORMATION
14.1.
Description of Study Vaccines
Ad26.ZEBOV
Ad26.ZEBOV is a monovalent, replication-incompetent Ad26-based vector that expresses the 
full length EBOV Mayinga GP and is produced in the human cell line PER.C6®.
The Ad26.ZEBOV vaccine will be supplied at a concentration of 1x1011 vp/mL in 2-mL 
single-use glass vials as a frozen liquid suspension to be thawed before use. Each vial contains 
an extractable volume of 0.5 mL. Refer to the Investigator's Brochure for a list of excipients.11
The drug substance used in Ad26.ZEBOV drug product is manufactured, according to the 2x10 L 
scale process, in Bern, Switzerland manufacturing facility.
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.12
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 
≤-60C and MVA-BN-Filo vials must be stored at ≤–20C.

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Vials must be stored in a secured location with no access for unauthorized personnel. All study 
product storage equipment (including refrigerators, freezers), must be equipped with a continuous 
temperature monitor and alarm, and with back-up power systems. In the event that study vaccine 
is exposed to temperatures outside the specified temperature ranges, all relevant data will be sent 
to the sponsor to determine if the affected study vaccine can be used or will be replaced. The 
affected study vaccine must be quarantined and not used until further instruction from the 
sponsor is received.
Blinding will be achieved by preparation of study vaccine by unblinded qualified study-site 
personnel not involved in any other study-related procedure, and by the administration of vaccine 
in a masked syringe by a blinded study vaccine administrator (see Definitions of Terms).
Details on the preparation, the holding time and storage conditions from the time of preparation 
to administration of Ad26.ZEBOV and MVA-BN-Filo are provided in the Site Investigational 
Product Procedures Manual.
14.4.
Study Vaccine Accountability
The investigator is responsible for ensuring that all study vaccine received at the site is 
inventoried and accounted for throughout the study. The study vaccine administered to the 
subject must be documented on the study vaccine accountability form. All study vaccine will be 
stored and disposed of according to the sponsor's instructions. Study-site personnel must not 
combine contents of the study vaccine containers.
Study vaccine must be handled in strict accordance with the protocol and the container label, and 
must be stored at the study site in a limited-access area or in a locked cabinet under appropriate 
environmental conditions. Unused study vaccine must be available for verification by the 
sponsor's study site monitor during on-site monitoring visits. The return to the sponsor of unused 
study vaccine will be documented on the study vaccine return form. When the study site is an 
authorized destruction unit and study vaccine supplies are destroyed on-site, this must also be 
documented on the study vaccine return form.
Potentially hazardous materials such as used ampules, needles, syringes and vials containing 
hazardous liquids, should be disposed of immediately in a safe manner and therefore will not be 
retained for study vaccine accountability purposes.
Study vaccine should be dispensed under the supervision of the investigator or a qualified 
member of the study-site personnel, or by a qualified staff member. Study vaccine will be 
supplied only to subjects participating in the study. Returned study vaccine must not be 
dispensed again, even to the same subject. Study vaccine may not be relabeled or reassigned for 
use by other subjects. The investigator agrees neither to dispense the study vaccine from, nor 
store it at, any site other than the study sites agreed upon with the sponsor.

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15.
STUDY-SPECIFIC MATERIALS
The investigator will be provided with the following supplies:

Investigator’s Brochures and addenda (if applicable) for Ad26.ZEBOV and MVA-BN-Filo 

Site investigational product procedures manual

Laboratory manual

IWRS manual 

Electronic Data Capture (eDC) manual/electronic CRF completion guidelines and 
randomization instructions

Sample ICF

Subject diaries

TOU

Rulers, thermometers

Site information card

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.
Approximately 571 to 675 mL of blood (including PBMC samples) will be drawn from adults
over a period of around 1 year, and remains well below the limits of standard blood donation.
Additional blood may be drawn to confirm and follow-up on adverse events.
Test of Understanding
The TOU is a short assessment of the subject’s understanding of key aspects of the study
(Attachment 1). The test will help the study staff to determine how well the subject understands 
the study and the requirements for participation.
The TOU must be completed after reading but before signing the ICF by all subjects (or as 
required per local regulations and practice, see Section 4), prior to enrollment into the study. The 
TOU is reviewed one-on-one with the subject and a member of the study team. Subjects are 
allowed to retake the test twice to achieve the passing score (≥90%) required for participation in 
the study. If a subject fails to achieve the passing score, further information and counseling will 
be provided by the study team member. 

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Any subject not capable of understanding the key aspects of the study, and their requirements for 
participation, should not be enrolled.
16.2.
Regulatory Ethics Compliance
16.2.1.
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the 
protocol, current ICH guidelines on Good Clinical Practice (GCP), and applicable regulatory and 
country-specific requirements.
GCP is an international ethical and scientific quality standard for designing, conducting, 
recording, and reporting studies that involve the participation of human subjects. Compliance 
with this standard provides public assurance that the rights, safety, and well-being of study 
subjects are protected, consistent with the principles that originated in the Declaration of 
Helsinki, and that the study data are credible.
16.2.2.
Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or sponsor where required) will provide the 
IEC/IRB with current and complete copies of the following documents (as required by local 
regulations):

Final protocol and, if applicable, amendments

Site-specific addendum

Sponsor-approved ICF (and any other written materials to be provided to the subjects)

Investigator's Brochure (or equivalent information) and amendments/addenda

TOU

Sponsor-approved subject recruiting materials

Information on compensation for study-related injuries or payment to subjects for 
participation in the study, if applicable

Investigator's curriculum vitae or equivalent information (unless not required, as 
documented by the IEC/IRB)

Information regarding funding, name of the sponsor, institutional affiliations, other potential 
conflicts of interest, and incentives for subjects

Any other documents that the IEC/IRB requests to fulfill its obligation
This study will be undertaken only after the IEC/IRB has given full approval of the final 
protocol, amendments (if any, excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct, unless required locally), the ICF, applicable 
recruiting materials, and subject compensation programs, and the sponsor has received a copy of 
this approval. This approval letter must be dated and must clearly identify the IEC/IRB and the 
documents being approved.

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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)

Site-specific addendum amendments

Revision(s) to ICF and any other written materials to be provided to subjects

If applicable, new or revised subject recruiting materials approved by the sponsor

Revisions to compensation for study-related injuries or payment to subjects for participation 
in the study, if applicable

New edition(s) of the Investigator's Brochure and amendments/addenda

Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at 
least annually)

Reports of adverse events that are serious, unlisted/unexpected, and associated with the 
study vaccine

New information that may adversely affect the safety of the subjects or the conduct of the 
study

Deviations from or changes to the protocol to eliminate immediate hazards to the subjects

Report of deaths of subjects under the investigator's care

Notification if a new investigator is responsible for the study at the site

Development Safety Update Report and Line Listings, where applicable

Any other requirements of the IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct), the amendment and applicable ICF revisions 
must be submitted promptly to the IEC/IRB for review and approval before implementation of 
the change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where 
required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB 
about the study completion.
16.2.3.
DoD Research Monitor
Each site will identify a DoD Research Monitor. The role and qualifications of the DoD 
Research Monitor are identified as follows: 
In their role as a full member of the PSRT, the DoD Research Monitor is required to review all 
unanticipated problems involving risk to volunteers or others, serious adverse events reports, and 
all volunteer deaths. The DoD Research Monitor will provide an unbiased written report of all 

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unanticipated problems involving risks to participants or others, and related serious adverse
events and deaths occurring at their site to the sponsor and the WRAIR IRB. At a minimum, the 
research monitor should comment on the outcomes of the event or problem, and in the case of a 
death, comment on the relationship to participation in the study. The research monitor should 
also indicate whether he/she concurs with the details of the report provided by the study 
investigator. The research monitor will also in the context of the PSRT: 

Discuss research progress with the PI and study team, interview subjects at their site, consult 
on individual cases, or evaluate suspected adverse reaction reports on behalf of the WRAIR 
IRB. 

At the direction of the WRAIR IRB, be involved in oversight functions (eg, observe 
recruitment, enrollment procedures, and the consent process for individuals, groups or units; 
oversee study interventions and interactions; review monitoring plans and unanticipated 
problems involving risks to subjects or others (UPIRTSO) reports; and oversee data 
matching, data collection, and analysis).

Promptly report discrepancies or problems to the WRAIR IRB. 

Have the authority, in the context of PSRT deliberations, to stop a research study in 
progress, remove individual subjects from a study, and take whatever steps are necessary to 
protect the safety and well-being of research subjects until the WRAIR IRB can assess the 
research monitor's report. 
Per ICH, Janssen Vaccines & Prevention B.V. as the sponsor has ultimate responsibility for the 
safety and well-being of participating subjects.
16.2.4.
Informed Consent
Each subject (or a legally acceptable representative) must give written consent according to local 
requirements after the nature of the study has been fully explained. The ICF(s) must be signed 
before performance of any study-related activity. The ICF(s) used must be approved by both the 
sponsor and by the reviewing IEC/IRB and be in a language that the subject can understand. The 
informed consent should be in accordance with principles that originated in the Declaration of 
Helsinki, current ICH and GCP guidelines, applicable regulatory requirements, and sponsor 
policy.
Before enrollment in the study, the investigator or an authorized member of the study-site 
personnel must explain to potential subjects or their legally acceptable representatives the aims, 
methods, reasonably anticipated benefits, and potential hazards of the study, and any discomfort 
participation in the study may entail. Subjects will be informed that their participation is 
voluntary and that they may withdraw consent to participate at any time. They will be informed 
that choosing not to participate will not affect the care the subject will receive. Finally, they will 
be told that the investigator will maintain a subject identification register for the purposes of 
long-term follow-up if needed and that their records may be accessed by health authorities and 
authorized sponsor personnel without violating the confidentiality of the subject, to the extent 
permitted by the applicable law(s) or regulations. By signing the ICF the subject or legally 
acceptable representative is authorizing such access. It also denotes that the subject agrees to 

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allow his or her study physician to recontact the subject for the purpose of obtaining consent for 
additional safety evaluations, if needed.
The subject or legally acceptable representative will be given sufficient time to read the ICF and 
the opportunity to ask questions. After this explanation and before entry into the study, consent 
should be appropriately recorded by means of either the subject's or his or her legally acceptable 
representative's personally dated signature. After having obtained the consent, a copy of the ICF 
must be given to the subject.
If the subject or legally acceptable representative is unable to read or write, an impartial witness 
should be present for the entire informed consent process (which includes reading and explaining 
all written information) and should personally date and sign the ICF after the oral consent of the 
subject or legally acceptable representative is obtained.
16.2.5.
Privacy of Personal Data
The collection and processing of personal data from subjects enrolled in this study will be 
limited to those data that are necessary to fulfill the objectives of the study.
These data must be collected and processed with adequate precautions to ensure confidentiality 
and compliance with applicable data privacy protection laws and regulations. Appropriate 
technical and organizational measures to protect the personal data against unauthorized 
disclosures or access, accidental or unlawful destruction, or accidental loss or alteration must be 
put in place. Sponsor personnel whose responsibilities require access to personal data agree to 
keep the identity of subjects confidential. The informed consent obtained from the subject (or his 
or her legally acceptable representative) includes explicit consent for the processing of personal 
data and for the investigator/institution to allow direct access to his or her original medical 
records (source data/documents) for study-related monitoring, audit, IEC/IRB review, and 
regulatory inspection. This consent also addresses the transfer of the data to other entities and to 
other countries.
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.
16.2.6.
Long-term Retention of Samples for Additional Future Research 
Samples collected in this study, for which consent has been obtained and for which additional 
material is available after study-specific testing is complete, may be stored for up to 15 years (or 

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according to local regulations) for potential future 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.
Stored samples will be coded throughout the sample storage and analysis process and will not be 
labeled with personal identifiers. Subjects may withdraw consent for their samples to be stored 
for potential future research at any time (see Section 10.3, Withdrawal From the Use of Research 
Samples). In such case, their blood samples will be destroyed after all the tests specified for this 
study have been concluded.
The sponsor will be responsible for the overall management of the sample inventory, shipping 
plan, allocation and storage of samples. The sponsor will establish a Material Transfer 
Agreement between all relevant parties (site, sponsor and the central laboratory charged with 
shipment and distribution of the samples). These Material Transfer Agreements will take into 
account national regulations and will be submitted for ethics approval and be in place before a 
site will be activated. Samples will be stored securely at facilities as directed by the sponsor.
16.2.7.
Country Selection
This study will only be conducted in those countries where the intent is to launch or otherwise 
help ensure access to the developed product if the need for the product persists, unless explicitly 
addressed as a specific ethical consideration in Section 16.1, Study-Specific Design 
Considerations.
17.
ADMINISTRATIVE REQUIREMENTS
17.1.
Protocol Amendments
Neither the investigator nor the sponsor will modify this protocol without a formal amendment 
by the sponsor. All protocol amendments must be issued by the sponsor, and signed and dated by 
the investigator. Protocol amendments must not be implemented without prior IEC/IRB 
approval, or when the relevant competent authority has raised any grounds for non-acceptance, 
except when necessary to eliminate immediate hazards to the subjects, in which case the 
amendment must be promptly submitted to the IEC/IRB and relevant competent authority. 
Documentation of amendment approval by the investigator and IEC/IRB must be provided to the 
sponsor. When the change(s) involve(s) only logistic or administrative aspects of the study, the 
IEC/IRB (where required) only needs to be notified.
During the course of the study, in situations where a departure from the protocol is unavoidable, 
the investigator or other physician in attendance will contact the appropriate sponsor 
representative listed in the Contact Information page(s), which will be provided as a separate
document). Except in emergency situations, this contact should be made before implementing 
any departure from the protocol. In all cases, contact with the sponsor must be made as soon as 
possible to discuss the situation and agree on an appropriate course of action. The data recorded 
in the CRF and source documents will reflect any departure from the protocol, and the source 
documents will describe this departure and the circumstances requiring it.

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17.2.
Regulatory Documentation
17.2.1.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities 
in each respective country, if applicable. A study may not be initiated until all local regulatory 
requirements are met.
17.2.2.
Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study vaccine to 
the study site:

Protocol and amendment(s), if any, signed and dated by the PI

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 PI, where required.

Signed and dated clinical trial agreement, which includes the financial agreement.

Any other documentation required by local regulations.
The following documents must be provided to the sponsor before enrollment of the first subject:

Completed investigator financial disclosure forms from all subinvestigators.

Documentation of subinvestigator qualifications (eg, curriculum vitae).

Name and address of any local laboratory conducting tests for the study, and a dated copy of 
current laboratory normal ranges for these tests, if applicable.

Local 
laboratory 
documentation 
demonstrating 
competence 
and 
test 
reliability 
(eg, accreditation/license), if applicable.

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17.3.
Subject Identification, Enrollment, and Screening Logs
The investigator agrees to complete a subject identification and enrollment log to permit easy 
identification of each subject during and after the study. This document will be reviewed by the 
sponsor study-site contact for completeness.
The subject identification and enrollment log will be treated as confidential and will be filed by 
the investigator in the study file. To ensure subject confidentiality, no copy will be made. All 
reports and communications relating to the study will identify subjects by subject identification 
and date of birth. In cases where the subject is not randomized into the study, the date seen and 
date of birth will be used.
The investigator must also complete a subject screening log, which reports on all subjects who 
were seen to determine eligibility for inclusion in the study.
17.4.
Source Documentation
At a minimum, source documents consistent in the type and level of detail with that commonly 
recorded at the study site as a basis for standard medical care, must be available for the 
following: subject identification, eligibility, and study identification; study discussion and date of 
signed informed consent; dates of visits; results of safety and immunogenicity parameters as 
required by the protocol; record of all adverse events and follow-up of adverse events; 
concomitant medication; study vaccine
receipt/dispensing/return records; study vaccine
administration information; and date of study completion and reason for early discontinuation of 
study vaccine or withdrawal from the study, if applicable.
The author of an entry in the source documents should be identifiable.
Specific details required as source data for the study and source data collection methods will be 
reviewed with the investigator before the study and will be described in the monitoring 
guidelines (or other equivalent document).
The information contained in the subject diary is primary data. Either the physical diary or diary 
information collected in the subject’s medical record will be considered a source document. 
Information from the diary provided to subjects to record solicited local and systemic adverse 
events until 7 days after each vaccination, will be reviewed by the investigator or designee to 
transcribe into the relevant parts of the CRF as described in the CRF Completion Guidelines.
17.5.
Case Report Form Completion
Case report forms are prepared and provided by the sponsor for each subject in electronic format.
All CRF entries, corrections, and alterations must be made by the investigator or authorized 
study-site personnel. The investigator must verify that all data entries in the CRF are accurate 
and correct.
The study data will be transcribed by study-site personnel from the source documents onto an 
electronic CRF, if applicable. Study-specific data will be transmitted in a secure manner to the 
sponsor.

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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, and periodic monitoring visits by the sponsor. Written 
instructions will be provided for collection, handling, storage, and shipment of samples.
Guidelines for CRF completion will be provided and reviewed with study-site personnel before 
the start of the study. The sponsor will review CRF for accuracy and completeness during on-site 
monitoring visits and after transmission to the sponsor; any discrepancies will be resolved with 
the investigator or designee, as appropriate. After upload of the data into the study database they 
will be verified for accuracy and consistency with the data sources.
17.7.
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all CRF 
and all source documents that support the data collected from each subject, as well as all study 
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a 
Clinical Trial, and all study documents as specified by the applicable regulatory requirement(s). 
The investigator/institution will take measures to prevent accidental or premature destruction of 
these documents.
Essential documents must be retained until at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. These documents will be 
retained for a longer period if required by the applicable regulatory requirements or by an 
agreement with the sponsor. It is the responsibility of the sponsor to inform the 
investigator/institution as to when these documents no longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who will 
accept the responsibility. The sponsor must be notified in writing of the name and address of the 
new custodian. Under no circumstance shall the investigator relocate or dispose of any study 
documents before having obtained written approval from the sponsor.

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If it becomes necessary for the sponsor, representatives from the WRAIR, United States Army 
Medical Research and Materiel Command (USAMRMC), the FDA, or the appropriate regulatory 
authority to review any documentation relating to this study, the investigator/institution must 
permit access to such reports.
17.8.
Monitoring
The sponsor will perform on-site monitoring visits as frequently as necessary. The monitor will 
record dates of the visits in a study site visit log that will be kept at the study site. The first 
post-initiation visit will be made as soon as possible after enrollment has begun. At these visits, 
the monitor will compare the data entered into the CRF with the source documents (eg, 
hospital/clinic/physician’s office medical records). The nature and location of all source 
documents will be identified to ensure that all sources of original data required to complete the 
CRF are known to the sponsor and study-site personnel and are accessible for verification by the 
sponsor study-site contact. If electronic records are maintained at the study site, the method of 
verification must be discussed with the study-site personnel.
Direct access to source documents (medical records) must be allowed for the purpose of 
verifying that the recorded data are consistent with the original source data. Findings from this 
review will be discussed with the study-site personnel. The sponsor expects that, during 
monitoring visits, the relevant study-site personnel will be available, the source documents will 
be accessible, and a suitable environment will be provided for review of study-related 
documents. The monitor will meet with the investigator on a regular basis during the study to 
provide feedback on the study conduct.
There will be independent monitoring of the pharmacy and preparation of study vaccines by an 
unblinded monitor (independent study vaccine monitor); regular monitors will be blinded.
In addition to on-site monitoring visits, remote contacts can occur. It is expected that during 
these remote contacts, study-site personnel will be available to provide an update on the progress 
of the study at the site.
17.9.
Regulatory Audits
The knowledge of any pending compliance inspection/visit by the US FDA, Office for Human 
Research Protections (OHRP), or other government agency concerning clinical investigation or 
research, the issuance of Inspection Reports, FDA Form 483, warning letters or actions taken by 
any regulatory agencies including legal or medical actions and any instances of serious or 
continuing noncompliance with the regulations or requirements will be reported immediately to 
the sponsor and WRAIR Human Subjects Protection Branch (HSPB). The WRAIR HSPB will 
report knowledge of any pending inspections/audits by regulatory agencies to the USAMRMC 
Office of Research Protections (ORP) Human Research Protection Office (HRPO).

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17.10. Study Completion/Termination
17.10.1.
Study Completion/End of Study
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.
17.10.2.
Study Termination
The sponsor reserves the right to close the study site or terminate the study at any time for any 
reason at the sole discretion of the sponsor. Study sites will be closed upon study completion. A 
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
17.11. On-site Audits
Representatives of the sponsor's clinical quality assurance department may visit the study site at 
any time during or after completion of the study to conduct an audit of the study in compliance 
with regulatory guidelines and company policy. These audits will require access to all study 
records, including source documents, for inspection. Subject privacy must, however, be 
respected. The investigator and study-site personnel are responsible for being present and 
available for consultation during routinely scheduled study-site audit visits conducted by the 
sponsor or its designees.
Similar auditing procedures may also be conducted by agents of any regulatory body, either as 
part of a national GCP compliance program or to review the results of this study in support of a 
regulatory submission. The investigator should immediately notify the sponsor if he or she has 
been contacted by a regulatory agency concerning an upcoming inspection.
17.12. Site-specific addendum
A site-specific addendum will be employed. The core protocol will be followed by all sites 
except for the differences noted in the site-specific addendum, which must be approved by the 
sponsor prior to submission to the IRBs and regulatory authorities.

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Status: Approved, Date: 18 September 2017
17.13. Use of Information and Publication
All information, including but not limited to information regarding Ad26.ZEBOV and 
MVA-BN-Filo or the sponsor's operations (eg, patent application, formulas, manufacturing 
processes, basic scientific data, prior clinical data, formulation information) supplied by the 
sponsor to the investigator and not previously published, and any data, including exploratory 
research data, generated as a result of this study, are considered confidential and remain the sole 
property of the sponsor. The investigator agrees to maintain this information in confidence and 
use this information only to accomplish this study, and will not use it for other purposes without 
the sponsor's prior written consent.
The investigator understands that the information developed in the study will be used by the 
sponsor in connection with the continued development of Ad26.ZEBOV and MVA-BN-Filo, and 
thus may be disclosed as required to other clinical investigators or regulatory agencies. To permit 
the information derived from the clinical studies to be used, the investigator is obligated to 
provide the sponsor with all data obtained in the study.
The results of the study will be reported in a Clinical Study Report generated by the sponsor and 
will contain data from all study sites that participated in the study as per protocol. Recruitment 
performance or specific expertise related to the nature and the key assessment parameters of the 
study will be used to determine a coordinating investigator. Results of exploratory analyses 
performed after the Clinical Study Report has been issued will be reported in a separate report 
and will not require a revision of the Clinical Study Report. Study subject identifiers will not be 
used in publication of results. Any work created in connection with performance of the study and 
contained in the data that can benefit from copyright protection (except any publication by the 
investigator as provided for below) shall be the property of the sponsor as author and owner of 
copyright in such work.
Consistent with Good Publication Practices and International Committee of Medical Journal 
Editors guidelines, the sponsor and consortium members shall have the right to publish such 
primary (multicenter) data and information without approval from the individual investigators. 
The individual investigators have the right to publish study site-specific data after the primary 
data are published. If an investigator wishes to publish information from the study, a copy of the 
manuscript must be provided to the sponsor for review at least 60 days before submission for 
publication or presentation. Expedited reviews will be arranged for abstracts, poster 
presentations, or other materials. If requested by the sponsor in writing, the investigator will 
withhold such publication for up to an additional 60 days to allow for filing of a patent 
application. In the event that issues arise regarding scientific integrity or regulatory compliance, 
the sponsor will review these issues with the investigator. The sponsor will not mandate 
modifications to scientific content and does not have the right to suppress information. For 
multicenter study designs and substudy approaches, secondary results generally should not be 
published before the primary endpoints of a study have been published. Similarly, investigators 
will recognize the integrity of a multicenter study by not submitting for publication data derived 
from the individual study site until the combined results from the completed study have been 
submitted for publication, within 12 months of the availability of the final data (tables, listings, 

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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graphs), or the sponsor confirms there will be no multicenter study publication. WRAIR 
recognizes the importance of communicating medical study data and therefore encourages their 
publication in reputable scientific journals and at seminars or conferences. Any results of 
medical investigations and or publication/lecture/manuscripts based thereon, shall be exchanged 
and discussed by the investigator and the USAMRMC prior to submission for publication or 
presentation.
Results from investigations shall not be made available to any third party by the investigating 
team outside the publication procedure as outlined previously. WRAIR will not quote from 
publications by investigators in its scientific information and/or promotional material without 
full acknowledgment of the source (i.e., author and reference). All publications written by 
WRAIR investigators must be reviewed and approved through the WRAIR publications approval 
process.
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.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Status: Approved, Date: 18 September 2017
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.
IMVANEX suspension for injection. UK Summary of Product Characteristics. Available at: 
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002596/human_med_0016
66.jsp&mid=WC0b01ac058001d124. Accessed 24 March 2015.
11.
Investigator’s Brochure: JNJ-61210474 (Ad26.ZEBOV), Edition 2.1. Crucell Holland B.V. (June 2015). For 
updated information, refer to Edition 4 (Janssen Vaccines & Prevention, 23 June 2016) and Addendum 1 for 
this edition (30 August 2016).
12.
Investigator’s Brochure: MVA-BN-Filo (MVA-mBN226B), Edition 5. Bavarian Nordic A/S (Mar 2015). For 
updated information, refer to Edition 10 (11 July 2016).
13.
Investigator’s Brochure: Ad26.ENVA.01 HIV-1 Vaccine, Edition 3. Crucell Holland B.V. (June 2013).
14.
Investigator’s Brochure: JNJ-55471468-AAA, JNJ-55471494-AAA, JNJ-55471520-AAA (Ad26.Mos.HIV) 
HIV 1 vaccine, Edition 2. Crucell Holland B.V. (Nov 2014).
15.
Investigator’s Brochure: JNJ-55471468-AAA, JNJ-55471494-AAA, JNJ-55471520-AAA (Ad26.Mos.HIV) 
HIV 1 vaccine, Addendum to Edition 2. Crucell Holland B.V. (Dec 2014).
16.
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.
17.
MVA-BN® (Modified Vaccinia Ankara - Bavarian Nordic). Available at: http://id.bavarian-
nordic.com/pipeline/technology-platform/mva-bn.aspx. Accessed 24 March 2015.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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Status: Approved, Date: 18 September 2017
18.
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.
19.
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.
20.
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.
21.
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.
22.
WHO Child Growth Standards (birth to 24 months). Available at: http://www.who.int/childgrowth/en.
Accessed 10 March 2015.

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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ATTACHMENTS
Attachment 1: Test of Understanding (TOU)
Note: A culturally appropriate translation will be made available to participating subjects.
Name participating subject:
Date:
Reviewer of the test:
Score:
Please read each question and answer whether the statement is True or False.
True
  
False
  
1.
The vaccines you will receive in this study will definitely protect against Ebola.
True
  
False
  
2.
In this study you will receive 2 injections of either vaccine or salt water.
True
  
False
  
3.
The vaccines in this study can give you Ebola.
True
  
False
  
4.
One purpose of this study is to determine if these vaccines are safe to administer to 
humans.
True
  
False
  
5.
Participants in this study will need to avoid engaging in activities that may expose them 
to Ebola virus.
True
  
False
  
6.
You may take other experimental (test) products while you are taking part in this study.
True
  
False
  
7.
You may withdraw from the study at any time if you choose.
True
  
False
  
8.
Women participating in this study are permitted to become pregnant during the study.
True
  
False
  
9.
A participant in this study may experience side effects after vaccination.
True
  
False
  
10. Some participants in this study may develop a positive Ebola test result, despite the fact 
that they do not have Ebola disease.

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Attachment 2: Toxicity Tables for Use in Trials Enrolling Healthy Adults
The abbreviations used in the following tables are:
ALT: alanine aminotransferase; aPTT: activated partial thromboplastin time; AST: aspartate aminotransferase; AV 
block: atrioventricular block; bpm: beats per minute; CK: creatine kinase; FEV1: forced expiratory volume in 
1 second; g: gram; HI: high; HPF: high power field; INR: international normalized ratio; IV: intravenous; LO: low; 
mEq: milliequivalent; mm Hg: millimeter of mercury; N: not graded; PT: prothrombin time; PTT: partial 
thromboplastin time; QTc: QT-interval corrected for heart rate; QTcB: Bazett’s corrected QT interval; QTcF: 
Fridericia’s corrected QT interval; RBC: red blood cell; Rx: therapy; ULN: upper limit of normal
CLINICAL ADVERSE EVENTS
Grading scale used for clinical adverse events is adapted from the Division of Microbiology and Infectious Diseases 
(DMID) Toxicity Tables (2014). For adverse events not included in the tables below, refer to the severity criteria 
guidelines in Section 12.1.3.
Cardiovascular
Grade 1
Grade 2
Grade 3
Arrhythmia
Asymptomatic, transient 
signs, no Rx required 
Recurrent/persistent; 
symptomatic Rx required 
Hemorrhage, blood loss 
Estimated blood loss 
≤100 mL 
Estimated blood loss 
>100 mL, no transfusion 
required
Transfusion required
QTcF (Fridericia’s 
correction) 1 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 baseline2
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
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
                                                
1 Inclusion dependent upon protocol requirements.
2 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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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/redness3
2.5-5 cm
5.1-10 cm
>10 cm
Induration/swelling4
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
                                                
3 In addition to grading the measured local reaction at the greatest single diameter, the measurement should be 
recorded as a continuous variable. 
4 Induration/swelling should be evaluated and graded using the functional scale as well as the actual measurement. 

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Arthralgia
Minimal symptoms; caused 
minimal or no interference 
with work, school or self-
care activities
Notable symptoms; 
required modification in 
activity or use of 
medications; did not result 
in loss of work or 
cancellation of social 
activities
Incapacitating symptoms; 
required bed rest and/or 
resulted in loss of work 
or cancellation of social 
activities
Chills
Minimal symptoms; caused 
minimal or no interference 
with work, school or self-
care activities
Notable symptoms; 
required modification in 
activity or use of 
medications; did not result 
in loss of work or 
cancellation of social 
activities
Incapacitating symptoms; 
required bed rest and/or 
resulted in loss of work 
or cancellation of social 
activities
LABORATORY TOXICITY GRADING
Grading scale used for lab assessments is based on ‘FDA’s Toxicity Grading Scale for Healthy Adult and 
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials’, but grade 3 and 4 are pooled below, 
consistent with the 3 scale toxicity grading used throughout the protocol. If a laboratory value falls within the 
grading as specified below but also within the local laboratory normal limits, the value is considered as normal. For 
hemoglobin only the change from reference is used for the grading. The FDA table does not include toxicity grading 
for hematocrit, RBC counts or INR. 
Blood, Serum, or Plasma Chemistries5
LO/HI/N 6
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 7
100-110
111-125
>125
HI 8
110-125
126-200
>200
Blood urea nitrogen 
HI
23-26 (mg/dL) 
or
8.3-9.4 
(mmol/L)
27-31 (mg/dL) 
or
9.5- 11.2 
(mmol/L) 
>31 (mg/dL) or
>11.2 
(mmol/L)
Creatinine 
N
1.5-1.7 
(mg/dL) or
133-151 
(µmol/L)
1.8-2.0 
(mg/dL) or
152-177 
(µmol/L)
>2.0 (mg/dL) 
or
> 177 (µmol/L)
Calcium (mg/dL)
LO
8.0-8.4
7.5-7.9
<7.5
HI
10.5-11.0
11.1-11.5
>11.5
Magnesium (mg/dL)
LO
1.3-1.5
1.1-1.2
<1.1
Phosphorus (mg/dL)
LO
2.3-2.5
2.0-2.2
<2.0
CK (mg/dL) 
N
1.25-1.5 x
ULN
1.6-3.0 x ULN
≥3.1 x ULN
Albumin (g/dL)
LO
2.8-3.1
2.5-2.7
<2.5
                                                
5 Depending upon the laboratory used, reference ranges, eligibility ranges and grading may be split out by sex and/or 
age.
6 Low, High, Not Graded.
7 Fasting.
8 Non-fasting.

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Total protein (g/dL)
LO
5.5-6.0
5.0-5.4
<5.0
Alkaline phosphatase (U/L)
N
1.1-2 x ULN
2.1-3 x ULN
>3 x ULN
AST (U/L)
HI
1.1-2.5 x ULN
2.6-5 x ULN
>5 x ULN
ALT (U/L)
HI
1.1-2.5 x ULN
2.6-5 x ULN
>5 x ULN
Bilirubin, serum total (mg/dL) – when 
accompanied by any increase in Liver 
Function Test 
1.1–1.25 x 
ULN
1.2 –1.5 x 
ULN
>1.5 x ULN
Bilirubin, serum total (mg/dL) – when 
Liver Function Test is normal
1.1–1.5 x ULN
1.6–2.0 x ULN
>2.0 x ULN
Amylase (U/L)
N
1.1-1.5 x ULN
1.6-2.0 x ULN
>2.0 x ULN
Lipase (U/L)
N
1.1-1.5 x ULN
1.6-2.0 x ULN
>2.0 x ULN
-
Hematology
LO/HI/N 9
Mild 
(Grade 1)
Moderate 
(Grade 2)
Severe 
(Grade 3)
Hemoglobin (women) change from 
baseline (g/dL)
Hemoglobin (men) change from 
baseline (g/dL)
LO
Any decrease-
1.5
1.6-2.0
>2.0
LO
Any decrease-
1.5
1.6-2.0
>2.0
White blood cell count (cell/mm3)
HI
10,800-15,000
15,001-20,000
>20,000
LO
2,500-3,500
1,500-2,499
<1,500
Lymphocytes (cell/mm3)
LO
750-1,000
500-749
< 500
Neutrophils (cell/mm3)*
LO
1,500-2,000
1,000-1,499
< 1000
Eosinophils (cell/mm3)
HI
650-1500
1501-5000
> 5000
Platelets (cell/mm3)
LO
125,000-
140,000
100,000-
124,000
<100,000
Coagulation
PT (seconds)
HI
1.0-1.10 x
ULN
1.11-1.20 x
ULN
>1.20 x ULN
International Normalized Ratio (INR)10
HI
1.1-1.5 x ULN
1.6-2.0 x ULN
>2.0 x ULN
PTT or aPTT (seconds)
HI
1.0-1.2 x ULN
1.21-1.4 x
ULN
>1.4 x ULN
Fibrinogen (mg/dL)
HI
400-500
501-600
>600
LO
150-200
125-149
<125 
Urine 
Protein (dipstick)
HI
Trace
1+
2+
Glucose (dipstick)
HI
Trace
1+
2+
Blood (microscopic) - red blood cells 
per high power field (RBC/HPF)
HI
1-10
11-50 
>50 and/or 
gross blood
* For African subjects, the following absolute neutrophil counts should be used to determine the severity level: 
grade 1 = 750 – 999 cell/uL; grade 2 = 500-749 cells/uL; grade 3 <500 cells/uL
                                                
9 Low, High, Not Graded.
10 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 11
Mild 
(Grade 1) 12
Moderate 
(Grade 2)
Severe 
(Grade 3)
Fever (°C)13
HI
38.0-38.4
38.5-38.9
>38.9
Fever (°F)
HI
100.4-101.1
101.2-102.0
>102.0
Tachycardia 
HI
101-115 bpm
116-130 bpm
>130 bpm or 
ventricular 
dysrhythmias
Bradycardia 
LO
50-54 or 45-50 
bpm 
if baseline 
<60 bpm
45-49 or 40-44 
bpm
if baseline 
<60 bpm
<45 or <40 bpm 
if baseline 
<60 bpm
Hypertension (systolic) - mm Hg14
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
                                                
11 Low, High, Not Graded.
12 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.
13 Axillary temperature. A protocol should select either °C or °F for inclusion.
14 Assuming subject is awake, resting, and supine; for adverse events, 3 measurements on the same arm with 
concordant results.

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

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INVESTIGATOR AGREEMENT
I have read this document 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 document and all pertinent information to all individuals responsible to me 
who assist in the conduct of this study. I will discuss this material with them to ensure that they are fully 
informed regarding the study vaccine, the conduct of the study, and the obligations of confidentiality.
Coordinating Investigator (where required):
Name (typed or printed):
Institution and Address:
Signature:
Date:
(Day Month Year)
Principal (Site) Investigator:
Name (typed or printed):
Institution and Address:
Telephone Number:
Signature:
Date:
(Day Month Year)
Sponsor's Responsible Medical Officer:
Name (typed or printed):
Cynthia Robinson, MD 
Institution:
Janssen Vaccines & Prevention B.V.
Signature:
[electronic signature appended at the end of the protocol]
Date:
(Day Month Year)
Note: If the address or telephone number of the investigator changes during the course of the study, written 
notification will be provided by the investigator to the sponsor, and a protocol amendment will not be required.
LAST PAGE

 
 
SIGNATURES 
 
 
 
 
Signed by  
Date  
 
Justification  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Georgi Shukarev
19Sep2017, 16:06:59 PM, UTC
Document Approval