A Multi-country, Prospective, Clinical Safety Study of Subjects Exposed to the Candidate Ebola Vaccines Ad26.ZEBOV and/or MVA-BN-Filo
Phase: PHASE3
Conditions: Hemorrhagic Fever, Ebola
Sponsor: Janssen Vaccines & Prevention B.V.

1
Status: Approved, Date: 2 March 2017
Janssen Vaccines & Prevention B.V. *
Clinical Protocol
A Multi-country, Prospective, Clinical Safety Study of Subjects Exposed to the Candidate 
Ebola Vaccines Ad26.ZEBOV and/or MVA-BN-Filo
Protocol VAC52150EBL4001; Phase 3
AMENDMENT 2
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.
EudraCT NUMBER:         2015-004139-11
Status:
Approved
Date:
2 March 2017
EDMS number:
EDMS-ERI-103280993, 5.0
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.
NCT02661464

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL4001 Amendment 2
2
Approved, Date: 2 March 2017
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
PROTOCOL AMENDMENTS....................................................................................................................... 4
SYNOPSIS.................................................................................................................................................... 7
TIME AND EVENTS SCHEDULE .............................................................................................................. 10
1.
COHORT 1: VACCINATED SUBJECTS .......................................................................................... 10
2.
COHORT 2: PREGNANCY OUTCOMES ......................................................................................... 11
3.
COHORT 3: OFFSPRING ................................................................................................................. 12
ABBREVIATIONS ...................................................................................................................................... 13
1.
INTRODUCTION................................................................................................................................ 14
1.1.
Background .................................................................................................................................... 14
1.2.
Benefit/Risk Section....................................................................................................................... 19
1.2.1.
Known Benefits........................................................................................................................... 19
1.2.2.
Potential Benefits........................................................................................................................ 20
1.2.3.
Known Risks............................................................................................................................... 20
1.2.4.
Potential Risks............................................................................................................................ 20
1.2.5.
Overall Benefit/Risk Assessment ............................................................................................... 20
1.3.
Overall Rationale for the Study...................................................................................................... 21
2.
OBJECTIVES AND HYPOTHESIS ................................................................................................... 21
2.1.
Objectives ...................................................................................................................................... 21
2.2.
Hypothesis ..................................................................................................................................... 21
3.
STUDY DESIGN AND RATIONALE ................................................................................................. 21
3.1.
Overview of Study Design.............................................................................................................. 21
3.2.
Study Design Rationale.................................................................................................................. 23
4.
TREATMENT ALLOCATION AND BLINDING................................................................................. 23
5.
SUBJECT POPULATION.................................................................................................................. 24
5.1.
Inclusion Criteria ............................................................................................................................ 24
5.2.
Exclusion Criteria ........................................................................................................................... 25
6.
DOSAGE AND ADMINISTRATION .................................................................................................. 25
7.
TREATMENT COMPLIANCE............................................................................................................ 25
8.
MEDICATION AND VACCINATIONS............................................................................................... 25
9.
STUDY EVALUATIONS .................................................................................................................... 25
9.1.
Study Procedures........................................................................................................................... 25
9.2.
Safety ............................................................................................................................................. 27
9.2.1.
Exposure Definition..................................................................................................................... 27
9.2.2.
Evaluations ................................................................................................................................. 27
9.2.3.
Endpoints.................................................................................................................................... 27
10.
SUBJECT COMPLETION/WITHDRAWAL FROM THE STUDY...................................................... 27
10.1.
Completion ..................................................................................................................................... 27
10.2.
Withdrawal From the Study............................................................................................................ 28
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VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL4001 Amendment 2
3
Approved, Date: 2 March 2017
11.
STATISTICAL METHODS................................................................................................................. 29
11.1.
Endpoints ....................................................................................................................................... 29
11.2.
Sample Size Determination ........................................................................................................... 29
11.3.
Analysis Sets.................................................................................................................................. 29
11.4.
Subject Information ........................................................................................................................ 30
11.5.
Safety Analyses ............................................................................................................................. 30
11.6.
Statistical Analysis ......................................................................................................................... 30
11.7.
Interim Analyses............................................................................................................................. 30
12.
ADVERSE EVENT REPORTING ...................................................................................................... 31
12.1.
Definitions ...................................................................................................................................... 31
12.1.1.
Adverse Event Definitions and Classifications ........................................................................... 31
12.1.2.
Attribution Definitions.................................................................................................................. 32
12.1.3.
Severity Criteria .......................................................................................................................... 33
12.2.
Special Reporting Situations.......................................................................................................... 33
12.3.
Procedures..................................................................................................................................... 33
12.3.1.
Serious Adverse Events ............................................................................................................. 33
12.3.2.
Pregnancy................................................................................................................................... 34
12.4.
Contacting Sponsor Regarding Safety........................................................................................... 34
13.
PRODUCT QUALITY COMPLAINT HANDLING.............................................................................. 34
14.
STUDY VACCINE INFORMATION ................................................................................................... 34
15.
STUDY-SPECIFIC MATERIALS....................................................................................................... 35
16.
ETHICAL ASPECTS ......................................................................................................................... 35
16.1.
Study-Specific Design Considerations........................................................................................... 35
16.2.
Regulatory Ethics Compliance....................................................................................................... 35
16.2.1.
Investigator Responsibilities ....................................................................................................... 35
16.2.2.
Independent Ethics Committee or Institutional Review Board ................................................... 36
16.2.3.
Informed Consent and Assent Form........................................................................................... 37
16.2.4.
Privacy of Personal Data ............................................................................................................ 38
17.
ADMINISTRATIVE REQUIREMENTS .............................................................................................. 39
17.1.
Protocol Amendments.................................................................................................................... 39
17.2.
Regulatory Documentation ............................................................................................................ 39
17.2.1.
Regulatory Approval/Notification ................................................................................................ 39
17.2.2.
Required Prestudy Documentation............................................................................................. 39
17.3.
Subject Identification, Enrollment, and Screening Logs ................................................................ 40
17.4.
Source Documentation................................................................................................................... 40
17.5.
Case Report Form Completion ...................................................................................................... 41
17.6.
Data Quality Assurance/Quality Control ........................................................................................ 42
17.7.
Record Retention ........................................................................................................................... 42
17.8.
Monitoring ...................................................................................................................................... 43
17.9.
Study Completion/End of Study..................................................................................................... 43
17.9.1.
Study Completion ....................................................................................................................... 43
17.9.2.
Study Termination....................................................................................................................... 43
17.10.
On-Site Audits ................................................................................................................................ 44
17.11.
Use of Information and Publication................................................................................................ 44
REFERENCES............................................................................................................................................ 46
INVESTIGATOR AGREEMENT ................................................................................................................. 47
LAST PAGE................................................................................................................................................ 47
NCT02661464

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL4001 Amendment 2
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Approved, Date: 2 March 2017
PROTOCOL AMENDMENTS
Protocol Version 
Issue Date
Original Protocol
25-Nov-2015
Amendment 1
30-Sep-2016
Amendment 2
This document
Amendments below are listed beginning with the most recent amendment.
Amendment_2 (this document)
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of Directive 
2001/20/EC of the European Parliament and the Council of the European Union.
The overall reason for the amendment: Originally, all subjects who were exposed to Ad26.ZEBOV and/or 
MVA-BN-Filo in a Phase 1, 2 or 3 clinical study were to be approached to consent for enrollment into the 
VAC52150EBL4001 study. With this amendment, this will no longer be the case. Each local authority will 
determine which cohorts will be opened for enrollment in their region. It is not mandatory to open all cohorts for 
enrollment. As a result, a local authority may restrict enrollment to 1 or 2 cohorts, rather than allowing enrollment
in all cohorts.
The original development plan (at the time of the ongoing Ebola epidemic in Africa) was an accelerated plan with 
the anticipation of conducting Phase 3 efficacy studies (with limited safety data collection) shortly after Phase 1 
and in parallel with Phase 2. The sponsor designed the VAC52150EBL4001 study for the extended follow-up of 
serious adverse events (SAEs) to enhance the ability for signal detection of rare events. Since there is no longer 
an ongoing Ebola epidemic, it is not currently possible to conduct a parallel Phase 3 efficacy study as part of an 
accelerated development plan. More controlled safety data will become available for all vaccinated subjects, 
therefore, prior to any potential future efficacy study.
The changes made to the clinical protocol VAC52150EBL4001 are listed below, including the rationale of each 
change and a list of all applicable sections.
Rationale: It was specified that each local authority will determine which cohorts will be opened for enrollment 
in their region. It is not mandatory to open all cohorts for enrollment. As a result, a local authority may restrict 
enrollment to 1 or 2 cohorts, rather than allowing enrollment in all cohorts. The approximate number of subjects 
potentially to be enrolled in this study was updated.
SYNOPSIS
3.1 Overview of Study Design
5 SUBJECT POPULATION
5.1 Inclusion Criteria
11.2 Sample Size Determination
Rationale: Updates were made to the Background section and references were added to the latest versions of the 
Investigator's Brochure of Ad26.ZEBOV and MVA-BN-Filo. In addition, the potential risk of myo/pericarditis 
was removed because no cardiovascular events were associated with the current MVA-BN-Filo vaccine.
1.1 Background
1.2 Benefit/Risk Section
1.2.4 Potential Risks
REFERENCES
Rationale: Minor editorial changes have been made throughout the document.
1.1 Background
5.1 Inclusion Criteria
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VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL4001 Amendment 2
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Approved, Date: 2 March 2017
Amendment_1 (30 September 2016)
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of Directive 
2001/20/EC of the European Parliament and the Council of the European Union.
The overall reason for the amendment: Since validated assays are not available yet to assess immune responses 
in the ongoing Phase 2 and 3 studies, unblinding of these studies has been delayed. Therefore, subjects who 
received placebo in their original Phase 2 or 3 study will also be approached for enrollment into the VAC52150 
Vaccine Development Roll-over study before unblinding of their original study.
The changes made to the clinical protocol VAC52150EBL4001 are listed below, including the rationale of each 
change and a list of all applicable sections.
Rationale: Unblinding of the ongoing Phase 2 and 3 studies has been delayed. Therefore, placebo subjects from 
these studies who reach the last study visit before unblinding of their original study, will be approached for 
enrollment into the VAC52150 roll-over study. Details on the procedures for these subjects have been added.
SYNOPSIS
Time and Events Schedule
3.1 Overview of Study Design
4 TREATMENT ALLOCATION AND BLINDING
5 SUBJECT POPULATION
8 Medication and Vaccinations
9.1 Study Procedures
9.2.1 Exposure Definition
9.2.2 Evaluations
10.1 Completion
10.2 Withdrawal From the Study
11.2 Sample Size Determination
11.4 Subject Information
11.5 Safety Analyses
12.3.2 Pregnancy
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
Rationale: Based on the request of the Food and Drug Administration, the study phase is updated to Phase 3.
Title Page
Rationale: Name change from Crucell Holland B.V. to Janssen Vaccines & Prevention B.V.
Title Page
1 INTRODUCTION
REFERENCES
INVESTIGATOR AGREEMENT
NCT02661464

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL4001 Amendment 2
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Approved, Date: 2 March 2017
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
1 INTRODUCTION
5 SUBJECT POPULATION
NCT02661464

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL4001 Amendment 2
7
Approved, Date: 2 March 2017
SYNOPSIS
A Multi-country, Prospective, Clinical Safety Study of Subjects Exposed to the Candidate Ebola Vaccines 
Ad26.ZEBOV and/or MVA-BN-Filo
The sponsor, in collaboration with Bavarian Nordic GmbH (BN), 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 Mayinga glycoprotein (GP) of the 
Ebola virus (EBOV, formerly known as Zaire ebolavirus), 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 
manufactured in chicken embryo fibroblast cells. The EBOV GP expressed by MVA-BN-Filo has 100% 
homology to the one expressed by Ad26.ZEBOV.
The EBOV GP that circulated in West Africa has 97% homology to the EBOV GP used in these vaccine 
regimens.
Ad26.ZEBOV and MVA-BN-Filo are being evaluated in Phase 1, 2 and 3 clinical studies, in different 
heterologous prime-boost regimens, in which one study vaccine is used to prime a filovirus-specific 
immune response and the other study vaccine is used to boost the immune response. Homologous 
regimens for each vaccine are also being evaluated.
OBJECTIVES AND HYPOTHESIS
Objectives
The study objectives are: 

To collect serious adverse event information from subjects exposed to Ad26.ZEBOV and/or MVA-
BN-Filo in a Phase 1, 2, or 3 clinical study, for a total of 60 months after prime vaccination 
(including the duration in the subject’s original study).

To collect pregnancy outcomes (including spontaneous/elective abortion, intrauterine death/stillbirth, 
information on delivery) and serious adverse event information during pregnancy from female 
subjects who became pregnant with estimated conception within 28 days after vaccination with 
MVA-BN-Filo or within 3 months after vaccination with Ad26.ZEBOV in a Phase 1, 2 or 3 clinical 
study.

To collect serious adverse event information for up to 60 months after birth from children born to 
female subjects who became pregnant with estimated conception within 28 days after vaccination 
with MVA-BN-Filo or within 3 months after vaccination with Ad26.ZEBOV in a Phase 1, 2 or 3 
clinical study.
Hypothesis
This is a descriptive study to document the long-term safety profile of Ad26.ZEBOV and MVA-BN-Filo
and to address gaps in the currently available data for the risks of Ad26.ZEBOV and/or MVA-BN-Filo. 
As this study aims to describe the data for benefit-risk assessment purposes, no hypotheses are pre-
specified.
NCT02661464

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL4001 Amendment 2
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Approved, Date: 2 March 2017
OVERVIEW OF STUDY DESIGN
This is a multi-country, prospective, long-term clinical safety study designed to extend the total follow-up 
period of vaccinated subjects up to 60 months (including the duration in the subject’s original study), to 
allow collection of serious adverse events and pregnancy outcomes (including spontaneous/elective 
abortion, intrauterine death/stillbirth, information on delivery) following administration of Ad26.ZEBOV 
and/or MVA-BN-Filo for the prevention of Ebola virus disease among subjects who participated in a 
Phase 1, 2 or 3 clinical study. In addition, offspring from vaccinated female subjects who became 
pregnant with estimated conception within 28 days after vaccination with MVA-BN-Filo or within 
3 months after vaccination with Ad26.ZEBOV in a Phase 1, 2 or 3 clinical study will be followed up to 
60 months after birth. Up to approximately 3,000 subjects may potentially be enrolled in this study, based 
on the number of exposed subjects in the contributing Phase 1, 2 or 3 clinical studies.
Since validated assays are not available yet to assess immune responses in the ongoing Phase 2 and 3 
studies, unblinding of these studies has been delayed. Therefore, subjects in the ongoing Phase 2 and 3 
studies who reach the last study visit will be approached to consent for enrollment into the VAC52150 
Vaccine Development Roll-over study for long-term safety surveillance (for a total of up to 60 months 
after the prime vaccination). After unblinding of their original study only subjects who received 
Ad26.ZEBOV and/or MVA-BN-Filo will remain in this VAC52150 Vaccine Development Roll-over 
study for long-term safety surveillance. After unblinding, subjects who received placebo and have already 
been enrolled into the VAC52150 Vaccine Development Roll-over study will be discontinued from 
further participation in this roll-over study. This also applies to pregnant subjects who received placebo
(ie, subjects enrolled in Cohort 2) or offspring from vaccinated female subjects who received placebo (ie, 
subjects enrolled in Cohort 3).
The study will consist of an enrollment visit, a number of follow-up contacts and an end-of-study contact. 
These contacts are preferably conducted by phone; if not possible, a study site visit needs to be organized.
Preferably, offspring from vaccinated female subjects will visit the study site for every study visit. If not 
possible, the child may be visited at home by study site staff or a qualified health care worker for data 
collection.
Data collection can start when a signed informed consent form (ICF) is available for the current study. 
Preferably, signing of the ICF occurs at the last visit of the subject’s original study (or at birth for 
offspring). If this is not possible, baseline data will be collected when a signed ICF is available and data 
need to be captured retrospectively up to the moment of enrollment in the current study.
Data collection will be as follows for the 3 cohorts:
Cohort 1: Data for subjects vaccinated with Ad26.ZEBOV and/or MVA-BN-Filo (or placebo) in a 
Phase 1, 2 or 3 clinical study (adults, adolescents and children) and who consent to participation in the 
current study will be collected in 6-month intervals. Data collection will continue for a total of 60 months 
after prime vaccination (including the duration in the subject’s original study).
Cohort 2: Data on the pregnancy outcome of female subjects who became pregnant with estimated 
conception within 28 days after vaccination with MVA-BN-Filo (or placebo) or within 3 months after 
vaccination with Ad26.ZEBOV (or placebo) in a Phase 1, 2 or 3 clinical study and who consent to 
participation in the current study will be collected at notification of the pregnancy, and at the end of the 
pregnancy. These subjects will be followed in Cohort 2 up to the end of their pregnancy. Thereafter, 
female subjects will continue to be followed in Cohort 1 (to reach a total of 60 months follow-up after 
prime vaccination including the duration in the subject’s original study); live-born children will be 
followed in Cohort 3.
Cohort 3: Data for children born to female subjects exposed to Ad26.ZEBOV and/or MVA-BN-Filo (or 
placebo) in a Phase 1, 2 or 3 clinical study who became pregnant with estimated conception within 
28 days after vaccination with MVA-BN-Filo (or placebo) or within 3 months after vaccination with 
NCT02661464

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL4001 Amendment 2
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Approved, Date: 2 March 2017
Ad26.ZEBOV (or placebo) and for whom consent for the current study is given, will be collected in 
6-month intervals, and up to 60 months after birth.
Each local authority will determine which cohorts will be opened for enrollment in their region. It is not 
mandatory to open all cohorts for enrollment. As a result, a local authority may restrict enrollment to 1 or 
2 cohorts, rather than allowing enrollment in all cohorts.
After unblinding of their original study, subjects from Cohort 1 and 2 who received placebo or offspring 
(Cohort 3) from female subjects who received placebo will be discontinued from further participation in 
this roll-over study.
SUBJECT POPULATION
The study will be open to subjects who participated in a Phase 1, 2 or 3 clinical study with Ad26.ZEBOV 
and/or MVA-BN-Filo and who received at least one dose of study vaccine (active vaccine or placebo).
SAFETY EVALUATIONS
Serious adverse event information in each cohort, pregnancy outcomes (including spontaneous/elective 
abortion, intrauterine death/stillbirth, information on delivery) and growth measurements for offspring 
will be collected.
STATISTICAL METHODS
There are no planned interim analyses. However, the accumulating data during study conduct may be 
used for reporting required for health authority submissions or other purposes. As this is a non-
comparative study without formal hypotheses, any interim data may be used for purely administrative 
purposes without having an impact on study conduct or need for statistical adjustments. All interim 
reporting must be approved by the study responsible physician and project statistician prior to conduct.
No formal statistical testing of safety data is planned. Incidence rates of serious adverse events in each 
cohort, of pregnancy overall and by pregnancy outcome (including spontaneous/elective abortion, 
intrauterine death/stillbirth, information on delivery) will be calculated for all events and the number of 
events per person-year (where applicable), with corresponding 2-sided 95% confidence intervals. 
Incidence rates will also be tabulated by age group.
Results for subjects who received active vaccine or placebo will be presented separately.
NCT02661464

NCT02661464

NCT02661464

NCT02661464

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL4001 Amendment 2
13
Approved, Date: 2 March 2017
ABBREVIATIONS
Ad26
adenovirus serotype 26
Ad26.ZEBOV
Ad26 vector expressing the glycoprotein of the Ebola virus Mayinga variant
AIDS
acquired immunodeficiency syndrome
BN
Bavarian Nordic
CRF
Case Report Form
EBOV
Ebola virus
eDC
Electronic Data Collection
EU
European Union
GCP
Good Clinical Practice
GP
glycoprotein
HIV
human immunodeficiency virus
ICF
Informed Consent Form
IEC
Independent Ethics Committee 
IM
intramuscular(ly)
IRB
Institutional Review Board 
MARV
Marburg virus
MVA
Modified Vaccinia Ankara
MVA-BN-Filo
Modified Vaccinia Ankara Bavarian Nordic vector expressing multiple filovirus proteins
NHP
non-human primates
NP
nucleoprotein
PCR
polymerase chain reaction
RNA
ribonucleic acid
SUDV
Sudan virus
SUSAR
Suspected Unexpected Serious Adverse Reaction
TAFV
Tai Forest Virus
TCID50
tissue culture infective dose
US
United States
VISP
vaccine induced seropositivity
vp
viral particles
WHO
World Health Organization
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VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL4001 Amendment 2
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Approved, Date: 2 March 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 GmbH (BN), 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 Mayinga glycoprotein (GP) of 
the Ebola virus (EBOV, formerly known as Zaire ebolavirus), 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.
The EBOV GP that circulated in West Africa has 97% homology to the EBOV GP used in these 
vaccine regimens.
Ad26.ZEBOV and MVA-BN-Filo are being evaluated in Phase 1, 2 and 3 clinical studies, as a 
heterologous prime-boost regimen that is administered in different sequences and schedules, in 
which one study vaccine is used to prime a filovirus-specific immune response and the other 
study vaccine is used to boost the immune response. 
For the most up-to-date nonclinical and clinical information regarding Ad6.ZEBOV and MVA-
BN-Filo, refer to the latest versions of the Investigator's Brochures and Addenda (if 
applicable).5,6 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 non-human primates (NHPs). Case fatality rates in Ebola
virus disease range from 25% to 90% (average: 50%), according to the World Health 
Organization (WHO).10 These viruses are highly prioritized by the United States (US) 
Government, who has defined them as ‘Category A’ agents, due to the high mortality rate of 
infected individuals. Currently, no licensed vaccine, treatment or cure exists for this disease. 
Filoviruses are named for their long, filamentous shape. Within this filamentous virus, a single 
19-kilobase (kb) negative-sense ribonucleic acid (RNA) genome encodes 7 proteins: the GP, the 
polymerase, the NP, the secondary matrix protein, the transcriptional activator, the polymerase 
cofactor, and the matrix protein. The virion surface is covered by homotrimers of the viral GP, 
which is believed to be the sole host attachment factor for filoviruses. Following cell entry, the 
NCT02661464

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL4001 Amendment 2
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Approved, Date: 2 March 2017
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.3
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 have been performed, 
to strengthen the robustness of the nonclinical efficacy data, and also to optimize the prime-boost 
schedule so as to obtain induction of protective immunity as quickly as possible, to specifically 
respond to the Ebola virus disease outbreak in West Africa. Complete survival was observed 
with 8-week heterologous regimens with Ad26.ZEBOV as prime and MVA-BN-Filo as boost, 
whereas a high dose of MVA-BN-Filo in these regimens was associated with complete 
protection against Ebola virus disease. Partial protection was observed with both MVA-BN-Filo 
as a prime immunization and a shorter prime/boost interval.
Toxicology
A 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. 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 14-day
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.
In an embryofetal and pre- and postnatal development study in female rabbits, there was no 
maternal or developmental toxicity following maternal exposure to the vaccine regimens during 
the premating and gestation period. All vaccine regimens elicited detectable EBOV GP-specific 
maternal antibody titers that were transferred to the fetuses.
Biodistribution
Single-dose biodistribution studies in rabbits were performed using the MVA-BN vector or the 
Ad26 vector in combination with another insert (Ad26.ENVA.01: an experimental, prophylactic 
NCT02661464

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL4001 Amendment 2
16
Approved, Date: 2 March 2017
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.
Clinical Studies
To date, the results of the primary analysis of 4 Phase 1 clinical studies with Ad26.ZEBOV 
and/or 
MVA-BN-Filo 
are 
available 
(VAC52150EBL1001,
VAC52150EBL1002, 
VAC52150EBL1003, and VAC52150EBL1004). Currently, the clinical program to assess the 
safety/tolerability and immunogenicity of Ad26.ZEBOV and MVA-BN-Filo consists of 
5 Phase 1 
(VAC52150EBL1001, 
VAC52150EBL1002, 
VAC52150EBL1003, 
VAC52150EBL1004,
and 
VAC52150EBL1005), 
3 Phase
2 
(VAC52150EBL2001,
VAC52150EBL2002, 
and 
VAC52150EBL2003) 
and 
3 
Phase 3 
clinical 
studies 
(VAC52150EBL3001, VAC52150EBL3002, and VAC52150EBL3003), where monovalent 
Ad26.ZEBOV vaccine and multivalent MVA-BN-Filo vaccine are combined in homologous or 
heterologous prime-boost regimens in which each vector is used to prime a filovirus-specific 
immune response followed by a boost immunization with the same or the other vector 2 to 
12 weeks later. To date, approximately 2700 healthy adult subjects have been enrolled in the
studies mentioned above. Two additional Phase 1 studies investigating MVA-BN-Filo have been 
performed (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.5,6
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 placebo-
controlled 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 an open-label, uncontrolled fashion in 
healthy adults. VAC52150EBL1001 has enrolled 87 subjects and primary analysis data for safety 
and immunogenicity are available for 85 subjects (performed when all subjects had completed 
their 21-day post-boost visit or discontinued earlier).2 No deaths or adverse events of special 
interest were reported. Two subjects in the 14-day regimen who experienced grade 3 neutropenia 
did not receive the boost vaccination as they met criteria for contraindications to boost (specified 
NCT02661464

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL4001 Amendment 2
17
Approved, Date: 2 March 2017
in the protocol), but continued scheduled assessments as planned. There were no serious adverse 
events related to the study vaccines.
In the placebo-controlled regimens, overall frequencies of solicited local and solicited systemic 
adverse events were higher after MVA-BN-Filo and Ad26.ZEBOV, relative to placebo. In 
addition, there was a trend towards higher overall frequencies of solicited local and solicited 
systemic events after Ad26.ZEBOV, relative to MVA-BN-Filo. This trend was not observed in 
the open-label 14-day regimen. The most frequent solicited local adverse event was injection site 
pain. The most common solicited systemic adverse events were fatigue, headache and myalgia. 
Grade 3 solicited local adverse events occurred in 3 subjects (injection site pain and injection site 
swelling in 1 subject each, injection site erythema in 2 subjects). These events occurred after 
Ad26.ZEBOV vaccination. Grade 3 solicited systemic events were also reported in 3 subjects 
(nausea and headache in 2 subjects each, myalgia and fatigue in 1 subject each). All these events 
occurred after Ad26.ZEBOV, except fatigue which occurred after placebo. The systemic events 
after Ad26.ZEBOV were considered to be at least possibly related to vaccination by the 
investigator. In the open-label regimen, no subjects experienced grade 3 solicited local events. 
Grade 3 solicited systemic events occurred in 3 subjects after Ad26.ZEBOV (chills and fatigue 
in 3 subjects each, headache in 2 subjects, pyrexia and nausea in 1 subject each). All were 
considered to be at least possibly related to vaccination by the investigator. No grade 3 solicited 
systemic events were reported after MVA-BN-Filo. All solicited (local or systemic) adverse 
events were transient in nature and resolved without sequelae. In the placebo-controlled 
regimens, the overall frequency of unsolicited adverse events was generally comparable between 
Ad26.ZEBOV, MVA-BN-Filo, and placebo recipients. In the open-label regimen, unsolicited 
adverse events were more common after Ad26.ZEBOV than after MVA-BN-Filo. 
Overall, the reported adverse events following vaccination were mild in the majority of 
subjects, transient in nature, and resolving without sequelae. These findings are consistent with 
the safety profiles observed for similar vaccines. The safety profile of the individual vaccines 
when used as prime was comparable to that when used as boost. 
There was no apparent influence of the prime-boost interval (28 days or 56 days) on the safety 
profiles of the vaccines. The 14-day prime-boost interval seemed to be associated with higher 
frequencies of solicited adverse events relative to the 28-day and 56-day prime-boost intervals; 
however, due to the open-label design of the 14-day regimen, knowledge of the treatment 
assignment may have biased subjects’ reporting. 
Both vaccination sequences tested (ie, Ad26.ZEBOV prime followed by MVA-BN-Filo boost 
and MVA-BN-Filo prime followed by Ad26.ZEBOV boost) were highly immunogenic and 
induced considerable humoral and cellular immune responses. Extending the interval between 
the prime and boost led to increased antibody responses (magnitude at a 56-day prime-boost 
interval was about 1.8 times higher than at a 28-day prime-boost interval), while the effect was 
less pronounced or the reverse for T cell responses. The induced immune responses were 
functional, as demonstrated by the neutralizing activity of the antibody responses in all subjects. 
The composition of induced T cell response was favorable, with a high percentage of 
NCT02661464

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL4001 Amendment 2
18
Approved, Date: 2 March 2017
polyfunctional T cells, which generally are thought to play a role in immunological memory and 
effector functions.
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. All planned 
128 subjects of VAC52150EBL1002 have received a prime dose, and 126 subjects have received 
a boost dose (2 subjects were withdrawn). No vaccine-related serious adverse events 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 both studies. 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 to 
date.
Safety data generated with the 2 vaccines are provided below however, for the most recent 
information regarding the safety data of the 2 vaccines, refer to the latest versions of the 
Investigator's Brochures.5,6
Safety Profile of Ad26.ZEBOV
Ad26.ZEBOV is a monovalent, replication-incompetent Ad26-based vaccine. Only limited 
clinical data are available for Ad26.ZEBOV. However, adenovirus vaccine programs with other 
gene inserts have revealed no significant safety issues.5,6
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 
NCT02661464

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL4001 Amendment 2
19
Approved, Date: 2 March 2017
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 adults who have a contraindication to 
the first or second generation smallpox vaccines including people with immune deficiencies and 
skin disorders.4 A Phase 3 clinical study has been performed in the US (POX-MVA-013). Results 
of completed and ongoing clinical studies of MVA-BN-based vaccines in more than 
8,100 individuals, including elderly, children and immunocompromised subjects in whom 
replicating vaccines are contraindicated, have shown that the platform displays high 
immunogenicity and a favorable safety profile.7 Across all clinical studies, no trends for 
unexpected or serious adverse reactions due to the product were detected. 
Safety 
information 
was 
combined 
from 
the 
first 
2 
studies 
of 
MVA-BN-Filo 
(VAC52150EBL1001 and VAC52150EBL1002). In general, MVA-BN-Filo has been shown to 
be well tolerated.6
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.8,9
1.2.
Benefit/Risk Section
For the most recent information about the benefit/risk assessment of Ad26.ZEBOV and MVA-
BN-Filo, refer to the latest versions of the Investigator's Brochures.5,6
1.2.1.
Known Benefits
The clinical benefit of prime-boost combinations of Ad26.ZEBOV and MVA-BN-Filo is to be 
established.
NCT02661464

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL4001 Amendment 2
20
Approved, Date: 2 March 2017
1.2.2.
Potential Benefits
Subjects may benefit from clinical testing and physical examination in the Phase 1, 2 and 3 
clinical studies and from continued contact for safety follow-up in the current study; others may 
benefit from the knowledge that they may aid in the development of an Ebola vaccine. 
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 considered in this 
study, taking into consideration that this rollover study does not include further administration of 
the candidate vaccines during the study period:
Vaccine Induced Seropositivity (VISP)
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. 
Pregnancy and Birth Control
The effect of the study vaccines on a fetus or nursing baby is unknown, as well as the effect on 
semen. Therefore, a pregnancy with estimated conception within 28 days of vaccination with 
MVA-BN-Filo or within 3 months of vaccination with Ad26.ZEBOV in a female subject 
vaccinated with Ad26.ZEBOV and/or MVA-BN-Filo in Phase 1, 2 or 3 clinical studies will be 
followed up in this study. This study includes no further requirements for birth control as all 
rollover subjects have completed the vaccination phase.
There may be other serious risks that are not known.
1.2.5.
Overall Benefit/Risk Assessment
Since this is an observational safety study, there is no additional risk by participating in this 
study.
NCT02661464

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL4001 Amendment 2
21
Approved, Date: 2 March 2017
1.3.
Overall Rationale for the Study
The safety profile of Ad26.ZEBOV and MVA-BN-Filo needs to be established through 
evaluation of safety data for periods longer than those that are available from the Phase 1, 2 and 
3 clinical studies. Extended follow-up permits the identification of serious adverse events not 
detected during initial follow-up period in the vaccine clinical study. A long-term observational
study will permit the collection of product safety information over an extended period of time, 
without affecting the requirement for brief clinical studies to support a responsive cycle of 
clinical development decisions. Additionally, the establishment of a long-term safety study for 
follow-up of subjects exposed to Ad26.ZEBOV and/or MVA-BN-Filo has been requested by 
Health Authorities of countries where Phase 1, 2 or 3 clinical studies will be conducted.
2.
OBJECTIVES AND HYPOTHESIS
2.1.
Objectives
This study will document the long-term safety profile of Ad26.ZEBOV and MVA-BN-Filo in 
subjects previously exposed to these vaccines in a Phase 1, 2, or 3 clinical study and aims to
address gaps in the currently available data for the risks of Ad26.ZEBOV and/or MVA-BN-Filo.
The study objectives are:

To collect serious adverse event information from subjects exposed to Ad26.ZEBOV and/or 
MVA-BN-Filo in a Phase 1, 2, or 3 clinical study, for a total of 60 months after prime 
vaccination (including the duration in the subject’s original study).

To collect pregnancy outcomes (including spontaneous/elective abortion, intrauterine 
death/stillbirth, information on delivery) and serious adverse event information during 
pregnancy from female subjects who became pregnant with estimated conception within 
28 days after vaccination with MVA-BN-Filo or within 3 months after vaccination with 
Ad26.ZEBOV in a Phase 1, 2 or 3 clinical study.

To collect serious adverse event information for up to 60 months after birth from children 
born to female subjects who became pregnant with estimated conception within 28 days 
after vaccination with MVA-BN-Filo or within 3 months after vaccination with 
Ad26.ZEBOV in a Phase 1, 2 or 3 clinical study.
2.2.
Hypothesis
This is a descriptive study to document the long-term safety profile of Ad26.ZEBOV and/or 
MVA-BN-Filo and to address gaps in the currently available data for the risks of Ad26.ZEBOV 
and/or MVA-BN-Filo. As this study aims to describe the data for benefit-risk assessment 
purposes, no hypotheses are pre-specified.
3.
STUDY DESIGN AND RATIONALE
3.1.
Overview of Study Design
This is a multi-country, prospective, long-term clinical safety study designed to extend the total 
follow-up period of vaccinated subjects up to 60 months (including the duration in the subject’s 
original study), to allow collection of serious adverse events and pregnancy outcomes (including 
NCT02661464

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL4001 Amendment 2
22
Approved, Date: 2 March 2017
spontaneous/elective abortion, intrauterine death/stillbirth, information on delivery) following 
administration of Ad26.ZEBOV and/or MVA-BN-Filo for the prevention of Ebola virus disease
among subjects who participated in a Phase 1, 2 or 3 clinical study. In addition, offspring from 
vaccinated female subjects who became pregnant with estimated conception within 28 days after 
vaccination with MVA-BN-Filo or within 3 months after vaccination with Ad26.ZEBOV in a 
Phase 1, 2 or 3 clinical study will be followed up to 60 months after birth. Up to approximately 
3,000 subjects may potentially be enrolled in this study, based on the number of exposed subjects 
in the contributing Phase 1, 2 or 3 clinical studies.
Since validated assays are not available yet to assess immune responses in the ongoing Phase 2 
and 3 studies, unblinding of these studies has been delayed. Therefore, subjects in the ongoing 
Phase 2 and 3 studies who reach the last study visit will be approached to consent for enrollment 
into the VAC52150 Vaccine Development Roll-over study for long-term safety surveillance (for 
a total of up to 60 months after the prime vaccination). After unblinding of their original study 
only subjects who received Ad26.ZEBOV and/or MVA-BN-Filo will remain in this VAC52150 
Vaccine Development Roll-over study for long-term safety surveillance. After unblinding, 
subjects who received placebo and have already been enrolled into the VAC52150 Vaccine 
Development Roll-over study will be discontinued from further participation in this roll-over 
study. This also applies to pregnant subjects who received placebo (ie, subjects enrolled in 
Cohort 2) or offspring from vaccinated female subjects who received placebo (ie, subjects 
enrolled in Cohort 3).
The study will consist of an enrollment visit, a number of follow-up contacts and an end-of-study 
contact. These contacts are preferably conducted by phone; if not possible, a study site visit 
needs to be organized. Preferably, offspring from vaccinated female subjects will visit the study 
site for every study visit. If not possible, the child may be visited at home by study site staff or a 
qualified health care worker for data collection.
Data collection can start when a signed informed consent form (ICF) is available for the current 
study. Preferably, signing of the ICF occurs at the last visit of the subject’s original study (or at 
birth for offspring). If this is not possible, baseline data will be collected when a signed ICF is 
available and data need to be captured retrospectively up to the moment of enrollment in the 
current study.
Data collection will be as follows for the 3 cohorts:
Cohort 1: Data for subjects vaccinated with Ad26.ZEBOV and/or MVA-BN-Filo (or placebo) in 
a Phase 1, 2 or 3 clinical study (adults, adolescents and children) and who consent to 
participation in the current study will be collected in 6-month intervals. Data collection will 
continue for a total of 60 months after prime vaccination (including the duration in the subject’s 
original study). 
Cohort 2: Data on the pregnancy outcome of female subjects who became pregnant with 
estimated conception within 28 days after vaccination with MVA-BN-Filo (or placebo) or within 
3 months after vaccination with Ad26.ZEBOV (or placebo) in a Phase 1, 2 or 3 clinical study 
NCT02661464

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL4001 Amendment 2
23
Approved, Date: 2 March 2017
and who consent to participation in the current study will be collected at notification of the 
pregnancy, and at the end of the pregnancy. These subjects will be followed in Cohort 2 up to the 
end of their pregnancy. Thereafter, female subjects will continue to be followed in Cohort 1 (to 
reach a total of 60 months follow-up after prime vaccination including the duration in the 
subject’s original study); live-born children will be followed in Cohort 3.
Cohort 3: Data for children born to female subjects exposed to Ad26.ZEBOV and/or MVA-BN-
Filo (or placebo) in a Phase 1, 2 or 3 clinical study 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 for whom consent for the current study is 
given will be collected in 6-month intervals and up to 60 months after birth.
Each local authority will determine which cohorts will be opened for enrollment in their region. 
It is not mandatory to open all cohorts for enrollment. As a result, a local authority may restrict 
enrollment to 1 or 2 cohorts, rather than allowing enrollment in all cohorts.
After unblinding of their original study, subjects from Cohort 1 and 2 who received placebo or 
offspring (Cohort 3) from female subjects who received placebo will be discontinued from 
further participation in this roll-over study.
The study is considered completed with the last data collection time point for the last subject 
participating in the study. Further details of study completion and termination procedures are 
presented in Section 17.9.
Relevant Independent Ethics Committee (IEC)/Institutional Review Board (IRB) and Health 
Authority approvals will be secured prior to initiating the study.
3.2.
Study Design Rationale
The prospective design of the study was chosen to specifically meet the study objectives. 
Prospective data collection facilitates active pharmacovigilance via real-time identification and 
reporting of serious adverse events and facilitates collection of a sufficient quantity of defined 
variables to address the study objectives of characterizing serious adverse events and pregnancy 
outcomes. The study design was chosen to observe long-term safety outcomes following 
Phase 1, 2 and 3 clinical studies.
4.
TREATMENT ALLOCATION AND BLINDING
This section is not applicable, since no vaccine will be administered in the current study and 
subjects are already unblinded in their original Phase 1, 2 or 3 clinical study.
Unblinding of the ongoing Phase 2 and 3 studies has been delayed. Therefore, under 
Amendment 1, subjects who received placebo in their original Phase 2 or 3 study will also be 
approached for enrollment into the VAC52150 roll-over study before unblinding of their original 
study.
NCT02661464

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL4001 Amendment 2
24
Approved, Date: 2 March 2017
5.
SUBJECT POPULATION
The study will be open to subjects who participated in a Phase 1, 2 and 3 clinical study with 
Ad26.ZEBOV and/or MVA-BN-Filo and who received at least one dose of study vaccine (active 
vaccine or placebo). Up to approximately 3,000 subjects may potentially be enrolled in this 
study, based on the number of exposed subjects in the contributing Phase 1, 2 or 3 clinical 
studies.
The inclusion and exclusion criteria for enrolling subjects in this study are described in the 
following 2 subsections. If there is a question about the inclusion or exclusion criteria below, the 
investigator must consult with the appropriate sponsor representative and resolve any issues 
before enrolling a subject in the study. Waivers are not allowed.
For a discussion of the statistical considerations of subject selection, refer to Section 11.2.
5.1.
Inclusion Criteria
Each potential subject must satisfy all of the following criteria to be enrolled in the current study:
1.
1.1
1.2
Criteria modified per amendment 1
Criterion modified per amendment 2
Male or female who participated in a Phase 1, 2 or 3 clinical study with Ad26.ZEBOV 
and/or MVA-BN-Filo and has been exposed to Ad26.ZEBOV and/or MVA-BN-Filo
(or placebo) (Cohort 1);
or
Female who participated in a Phase 1, 2 or 3 clinical study with Ad26.ZEBOV and/or 
MVA-BN-Filo and 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) (Cohort 2);
or
Child born to a female subject exposed to Ad26.ZEBOV and/or MVA-BN-Filo (or 
placebo) in a Phase 1, 2, or 3 clinical study 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) (Cohort 3).
Note: Each local authority will determine which cohorts will be opened for enrollment 
in their region. It is not mandatory to open all cohorts for enrollment. As a result, a 
local authority may restrict enrollment to 1 or 2 cohorts, rather than allowing 
enrollment in all cohorts.
NCT02661464

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL4001 Amendment 2
25
Approved, Date: 2 March 2017
2.
Must sign an ICF for the current study (or their legally acceptable representative must 
sign) indicating that he or she understands the purpose of, and procedures required for,
the study and is willing to participate in the study (or let their child participate).
Note: Assent is also required of children capable of understanding the nature of the 
study (typically 7 years of age and older) as described in Section 16.2.3.
5.2.
Exclusion Criteria
No exclusions beyond those not meeting the inclusion criteria will be made for participation.
6.
DOSAGE AND ADMINISTRATION
This section is not applicable, since no vaccine will be administered in the current study. For 
details on the administered study vaccine, refer to the protocol of the subject’s original study.
7.
TREATMENT COMPLIANCE
This section is not applicable, since no study vaccine will be administered in the current study.
8.
MEDICATION AND VACCINATIONS
After a signed ICF is obtained for the current study, medications taken for serious adverse events 
occurring within the entire study follow-up period of 60 months after prime vaccination (ie,
limited to medication taken within a period of 30 days prior to the onset of a serious adverse 
event and up to the resolution of the serious adverse event), or vaccinations administered since 
exposure to Ad26.ZEBOV and/or MVA-BN-Filo (or placebo) (including routine vaccinations for 
children) will be documented from baseline (if not already present in the analysis data set from 
the subject’s original study) until the end of data collection. 
9.
STUDY EVALUATIONS
9.1.
Study Procedures
The Time and Events Schedule summarizes the frequency and timing of data collection in this 
study. The documentation of data must be performed according to Good Clinical Practice (GCP)
and professional guidelines. 
Prior to data collection, all subjects or their parent/legally acceptable representative (where 
applicable) must sign an ICF for the current study indicating that he or she understands the 
purpose of and procedures required for the study and is willing to participate in the study or let 
their child participate. Preferably, consent will be obtained at the last visit of the subject’s 
original study or at birth for offspring. If this is not possible, the consent can be given at a later 
time point, allowing collection of baseline data to be conducted retrospectively up to the moment 
of enrollment in the current study. Relevant data should be copied from the analysis data set of 
the subject’s original study. Any relevant new information should be added to the CRF of the 
current study.
NCT02661464

VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
Clinical Protocol VAC52150EBL4001 Amendment 2
26
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Where available (and applicable to the cohort), the following items are to be documented or 
captured from the original analysis data set at baseline and/or during the long-term follow-up 
period:

Demographic data (at baseline only);

Serious adverse events

Any medication taken within a period of 30 days prior to the onset of a serious adverse event 
and up to the resolution of serious adverse event;

Vaccinations (including routine vaccinations for children);

Pregnancy follow-up, including information on obstetric history, maternal/paternal risk 
factors, pregnancy outcome (including spontaneous/elective abortion, intrauterine 
death/stillbirth, information on delivery);

Follow-up of offspring, including information on birth (preterm/full term), growth 
measurements at birth and subsequent visits (height and weight, including growth 
percentiles), presence of birth defects, medical interventions beyond routine interventions at 
birth. Medical history of the child may include relevant information from the mother’s 
pregnancy follow-up, family history of growth (details on stature of parents and siblings).
Participating sites will enter data into the CRF into an electronic data collection (eDC) system. 
The CRF will direct the site regarding which data are required for collection. Participating sites 
will be trained on the use of the eDC system. Data collected should be recorded accurately, 
correctly and promptly for each subject during the study. Further details of CRF completion 
procedures are presented in Section 17.5.
The sponsor will perform on-site monitoring visits as frequently as necessary. The monitor will 
record dates of the visits in a site visit log that will be kept at the participating site. Further 
details of monitoring procedures are presented in Section 17.8.
When an enrolled subject completes or withdraws from the study, the investigator will complete 
an end-of-study form for the individual subject and provide a specific date for the end-of-study 
observation(s). When a subject withdraws before completing the study, the reason for withdrawal 
is to be documented in the CRF and in the source documents (see Section 10 for details).
After unblinding of their original study, subjects who received placebo will be withdrawn from 
further participation. This also applies to pregnant subjects who received placebo (ie, subjects 
enrolled in Cohort 2) or offspring from vaccinated female subjects who received placebo (ie, 
subjects enrolled in Cohort 3).
Subjects who appear to be lost to follow-up will be contacted, per local practice, and the data 
recorded in the CRF. Subjects unable to be reached within 365 days of their last follow-up will 
be considered “lost to follow-up” unless subsequent contact is established. Subjects lost to 
follow-up will have all data included for analysis unless the subject had specified upfront that
their data is to be excluded from analysis.
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9.2.
Safety
9.2.1.
Exposure Definition
Exposure to Ad26.ZEBOV and/or MVA-BN-Filo vaccines (or placebo) will be determined by 
documentation from the Phase 1, 2 and 3 clinical studies. The exposure date to any component of 
Ad26.ZEBOV and/or MVA-BN-Filo (or placebo) for each subject will be the vaccine 
administration date as obtained from the CRF from the subject’s original study.
9.2.2.
Evaluations 
Serious Adverse Events
For the prospective study period, all serious adverse events, related or not related, following 
exposure of subjects to Ad26.ZEBOV and/or MVA-BN-Filo (or placebo) or in offspring are to 
be recorded in the CRF and in the subject’s source documents.
Section 12 provides further details of safety reporting procedures.
Any serious adverse events 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.
Pregnancy Outcomes
For the prospective study period, all pregnancy outcomes (including spontaneous/elective 
abortion, intrauterine death/stillbirth, information on delivery) following pregnancy of a female 
subject 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) are to be recorded in the CRF and in the subject’s source documents.
Growth Measurements
For the prospective study period, growth measurements for offspring (including height, weight 
and growth percentiles) are to be recorded in the CRF and in the subject’s source documents. 
9.2.3.
Endpoints
Refer to Section 11.1 for the endpoints.
10.
SUBJECT COMPLETION/WITHDRAWAL FROM THE STUDY
When an enrolled subject completes or withdraws from the study, the investigator will complete 
an end-of-study form for the individual subject and provide a specific date for the end-of-study 
observation(s). 
10.1.
Completion
Cohort 1: Data for subjects vaccinated with Ad26.ZEBOV and/or MVA-BN-Filo (or placebo) in 
a Phase 1, 2 or 3 clinical study (adults, adolescents and children) and who consent to 
participation in the current study will be collected in 6-month intervals. Data collection will 
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continue for a total of 60 months after prime vaccination (including the duration in the subject’s 
original study).
Cohort 2: Data on the pregnancy outcome of female subjects who became pregnant with 
estimated conception within 28 days after vaccination with MVA-BN-Filo (or placebo) or within 
3 months after vaccination with Ad26.ZEBOV (or placebo) in a Phase 1, 2 or 3 clinical study 
and who consent to participation in the current study will be collected at notification of the 
pregnancy, and at the end of the pregnancy. These subjects will be followed in Cohort 2 up to the 
end of their pregnancy. Thereafter, female subjects will continue to be followed in Cohort 1 (to 
reach a total of 60 months follow-up after prime vaccination including the duration in the 
subject’s original study); live-born children will be followed in Cohort 3.
Cohort 3: Data for children born to female subjects exposed to Ad26.ZEBOV and/or MVA-BN-
Filo (or placebo) in a Phase 1, 2 or 3 clinical study 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 for whom consent for the current study is 
given will be collected in 6-month intervals, and up to 60 months after birth.
Refer to Section 10.2 for details on the withdrawal of subjects after unblinding of their original 
study.
10.2.
Withdrawal From the Study
A subject may be withdrawn from data collection in this study for any of the following reasons:

Withdrawal of consent

Lost to follow-up

Death 
After unblinding of their original study, subjects who received placebo will be withdrawn from 
further participation. This also applies to pregnant subjects who received placebo (ie, subjects 
enrolled in Cohort 2) or offspring from vaccinated female subjects who received placebo (ie, 
subjects enrolled in Cohort 3).
Subjects who are subsequently enrolled as a subject in another non-sponsor clinical study do not 
need to be withdrawn from the study. It is accepted that data collection in this study may be 
restricted by confidentiality agreement terms and/or conditions of another concurrent clinical 
study. 
When a subject withdraws before completing the study, the reason for withdrawal is to be 
documented in the CRF and in the source documents.
If a subject is lost to follow-up, every reasonable effort must be made by the study-site personnel 
to contact the subject and determine the reason for withdrawal. The measures taken to follow up 
must be documented. In the event that the status of the subject cannot be determined and the 
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subject is considered to be lost to follow-up, an end-of-study form for the individual subject will 
be completed and a specific date for the last observation will be provided.
11.
STATISTICAL METHODS
Statistical analysis will be performed by or under the authority of the sponsor. A general 
description of the statistical methods to be used to analyze the data collected in this study is 
outlined below. Specific details will be provided in the Statistical Analysis Plan.
11.1.
Endpoints
The following endpoints will be analyzed:

Incidence of serious adverse events in subjects exposed to Ad26.ZEBOV and/or MVA-BN-
Filo in a Phase 1, 2 or 3 clinical study, up to 60 months after prime vaccination.

Incidence of pregnancy with estimated conception within 28 days after vaccination with 
MVA-BN-Filo or within 3 months after vaccination with Ad26.ZEBOV.

Incidence of pregnancy by pregnancy outcome.

Incidence of live-born children from a pregnancy with estimated conception within 28 days 
after vaccination with MVA-BN-Filo or within 3 months after vaccination with 
Ad26.ZEBOV.

Incidence of serious adverse events in children born from a pregnancy with estimated 
conception within 28 days after vaccination with MVA-BN-Filo or within 3 months after 
vaccination with Ad26.ZEBOV up to 60 months after birth.
11.2.
Sample Size Determination
The enrollment projections of the contributing Phase 1, 2 and 3 clinical studies are estimated to 
result in enrollment of up to approximately 3,000 subjects.
The proposed study is based on analysis of prospective cohort data provided by investigators on
subjects exposed to Ad26.ZEBOV and/or MVA-BN-Filo (or placebo). The study may include 
bias related to the observational nature of the data and potential lack of data due to loss to 
follow-up or essential data not collected routinely. Loss to follow-up may be pronounced in 
countries where infrastructure for data collection is lacking. Additionally, the study’s ability to 
detect serious adverse events and the precision of these rates are based on the number of subjects 
participating in the study and completing study follow-up; however, this number is unknown.
11.3.
Analysis Sets
The Full Analysis set includes all subjects who were enrolled in this study and have at least one 
post-baseline visit, regardless of the occurrence of protocol violations. 
The Restricted Analysis set includes all subjects who were enrolled in this study and have at least 
one post-baseline visit, have no major protocol deviations deemed to affect safety endpoints and 
have not been enrolled in any other clinical study.
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The study endpoints will be analyzed based on the Full Analysis set as the primary analysis 
population. Additionally, the study endpoints may be analyzed based on the Restricted Analysis 
set as a secondary analysis population (sensitivity analysis).
11.4.
Subject Information
Baseline characteristics as recorded in the subject’s original study, including demographics, 
medical and vaccination history will be summarized by cohort and original randomization (active 
vaccine versus placebo). Categorical variables will be summarized by frequency distribution 
(number and percentage of subjects) and continuous variables will be summarized by descriptive 
statistics (including mean, median, standard deviation).
11.5.
Safety Analyses
The verbatim terms used in the CRF by investigators to document serious adverse events will be 
coded using the Medical Dictionary for Regulatory Activities (MedDRA). All serious adverse 
events will be included in the analysis. For each serious adverse event, the percentage of subjects 
who experience at least 1 occurrence of the given event and the number of events per person-
year (where applicable) with corresponding 2-sided 95% confidence intervals will be provided, 
for each cohort and by original randomization (active vaccine versus placebo). In addition, these 
analyses will be provided by age group for Cohort 1.
The incidence of pregnancy, incidence of pregnancy outcomes (including spontaneous/elective 
abortion, intrauterine death/stillbirth, information on delivery) and incidence of live-born 
children will be summarized by original randomization (active vaccine versus placebo). Only 
pregnancies with estimated conception within 28 days after vaccination with MVA-BN-Filo or 
within 3 months after vaccination with Ad26.ZEBOV, and live-born children from these 
pregnancies, will be included.
Results for subjects who received active vaccine or placebo will be presented separately.
A summary for subjects who die or who discontinue due to a serious adverse event will be 
provided.
The use of medications taken in relation to serious adverse events will be summarized.
Additional summaries, listings, datasets, or subject narratives may be provided, as appropriate.
11.6.
Statistical Analysis 
No formal statistical testing of safety data is planned. 
11.7.
Interim Analyses
There are no planned interim analyses. However, the accumulating data during study conduct 
may be used for reporting required for health authority submissions or other purposes. As this is 
a non-comparative study without formal hypotheses, any interim data may be used for purely 
administrative purposes without having an impact on study conduct or need for statistical 
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adjustments. All interim reporting must be approved by the study responsible physician and 
project statistician prior to conduct.
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
Serious Adverse Event
A serious adverse event based on ICH and EU Guidelines on Pharmacovigilance for Medicinal 
Products for Human Use is any untoward medical occurrence that at any dose:

Results in death

Is life-threatening
(The subject was at risk of death at the time of the event. It does not refer to an event that 
hypothetically might have caused death if it were more severe.)

Requires inpatient hospitalization or prolongation of existing hospitalization

Results in persistent or significant disability/incapacity

Is a congenital anomaly/birth defect

Is a suspected transmission of any infectious agent via a medicinal product

Is Medically Important*
*Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
also appropriate in other situations, such as important medical events that may not be 
immediately life threatening or result in death or hospitalization but may jeopardize the subject 
or may require intervention to prevent one of the other outcomes listed in the definition above. 
These should usually be considered serious.
If a serious and unexpected adverse event occurs for which there is evidence suggesting a causal 
relationship between the study vaccine and the event, the event must be reported as a serious and 
unexpected suspected adverse reaction (SUSAR) even if it is a component of the study endpoint 
(eg, all-cause mortality).
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 Ad6.ZEBOV and MVA-BN-Filo, the 
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expectedness of an adverse event will be determined by whether or not it is listed in the 
Investigator's Brochure and Addenda, if applicable. 5,6
Adverse Event With a Causal Relationship to a Study Vaccine
An adverse event is considered to have a causal relationship to a study vaccine if the attribution 
is possible, probable, or very likely by the definitions listed in Section 12.1.2.
An adverse event is considered to have no causal relationship to the study vaccine if the 
attribution is not related or doubtful by the definitions listed in Section 12.1.2.
12.1.2.
Attribution Definitions
Every effort should be made by the investigator to explain any adverse event and to assess its 
potential causal relationship, ie, to administration of the study 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 study 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 study vaccine. An alternative explanation, 
eg, concomitant drug(s), concomitant disease(s), is inconclusive. The relationship in time is 
reasonable; therefore, the causal relationship cannot be excluded.
Probable
An adverse event that might be due to the use of the study 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.
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12.1.3.
Severity Criteria 
An assessment of severity grade will be made using the following general categorical 
descriptors:
Mild: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not 
interfering with everyday activities.
Moderate: Sufficient discomfort is present to cause interference with normal activity.
Severe: Extreme distress, causing significant impairment of functioning or incapacitation. 
Prevents normal everyday activities.
The investigator should use clinical judgment in assessing the severity of events not directly 
experienced by the subject (eg, laboratory abnormalities).
12.2.
Special Reporting Situations
Safety events of interest on a sponsor study vaccine that may require expedited reporting and/or 
safety evaluation include, but are not limited to:

Adverse events of special interest known for Ad26.ZEBOV and MVA-BN-Filo5,6
These safety events may not meet the definition of an adverse event; however, from a policy 
perspective, they are treated in the same manner as adverse events. Any special situation that 
meets the criteria of a serious adverse event should be recorded on a Serious Adverse Event 
Report Form and be reported to the local sponsor within 24 hours of them becoming aware of the 
event.
12.3.
Procedures
12.3.1.
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
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
The event can be attributed to agents other than the study drug or to factors unrelated to 
study conduct

It becomes unlikely that any additional information can be obtained (subject or health care 
practitioner refusal to provide additional information, lost to follow-up after demonstration 
of due diligence with follow-up efforts)
Suspected transmission of an infectious agent by a medicinal product will be reported as a 
serious adverse event. Any event requiring hospitalization (or prolongation of hospitalization) 
that occurs during the course of a subject's participation in a study must be reported as a serious 
adverse event, except hospitalizations for the following:

Hospitalizations not intended to treat an acute illness or adverse event (eg, social reasons 
such as pending placement in long-term care facility)

Surgery or procedure planned before entry into the study (must be documented in the CRF). 
Note: Hospitalizations that were planned before the signing of the ICF for the current study, 
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.
12.3.2.
Pregnancy 
All initial reports of pregnancy in the Phase 1, 2 or 3 trials 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) in female subjects must have been reported to the sponsor by the 
study-site personnel as described in the respective protocols. Data collection for the pregnancy 
outcomes (including spontaneous/elective abortion, intrauterine death/stillbirth, information on 
delivery) will be performed in this study, as well as collection of serious adverse events 
occurring in the offspring from these subjects.
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
This section is not applicable, since no study vaccine will be administered in this study.
14.
STUDY VACCINE INFORMATION
This section is not applicable, since no study vaccine will be administered in this study.
For details on the administered study vaccine in the subject’s original Phase 1, 2 or 3 study, refer 
to the respective protocol.
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15.
STUDY-SPECIFIC MATERIALS
The investigator will be provided with the following supplies:

Investigator's Brochure’s and Addenda, if applicable

eDC Manual/electronic CRF Completion Guidelines 

Sample ICF
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 and benefits, 
and who provide their consent voluntarily will be enrolled.
When referring to the signing of the ICF, the terms legal guardian and legally acceptable 
representative refer to the legally appointed guardian of the child with authority to authorize 
participation in research. For each subject, his or her parent(s) (preferably both parents, if 
available) or a legally acceptable representative(s), as required by local regulations, must give 
written consent (permission) according to local requirements after the nature of the study has been 
fully explained and before the performance of any study-related assessments. Assent must be 
obtained from children (minors) capable of understanding the nature of the study, typically subjects 
7 years of age and older, depending on the institutional policies. For the purposes of this study, all 
references to subjects who have provided consent (and assent as applicable) refers to the subjects 
and his or her parent(s) or the subject's legal guardian(s) or legally acceptable representative(s) 
who have provided consent according to this process. Minors who assent to a study and later 
withdraw that assent should not be maintained in the study against their will, even if their parents 
still want them to participate.
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.
Good Clinical Practice is an international ethical and scientific quality standard for designing, 
conducting, recording, and reporting studies that involve the participation of human subjects. 
Compliance with this standard provides public assurance that the rights, safety, and well-being of 
study subjects are protected, consistent with the principles that originated in the Declaration of 
Helsinki, and that the study data are credible.
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16.2.2.
Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or sponsor where required) will provide the 
IEC/IRB with current and complete copies of the following documents (as required by local 
regulations):

Final protocol and, if applicable, amendments

Sponsor-approved ICF (and any other written materials to be provided to the subjects)

Investigator's Brochure (or equivalent information) and amendments/addenda

Sponsor-approved subject recruiting materials

Information on compensation for study-related injuries or payment to subjects for 
participation in the study, if applicable

Investigator's curriculum vitae or equivalent information (unless not required, as 
documented by the IEC/IRB)

Information regarding funding, name of the sponsor, institutional affiliations, other potential 
conflicts of interest, and incentives for subjects

Any other documents that the IEC/IRB requests to fulfill its obligation
This study will be undertaken only after the IEC/IRB has given full approval of the final 
protocol, amendments (if any, excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct, unless required locally), the ICF, applicable 
recruiting materials, and subject compensation programs, and the sponsor has received a copy of 
this approval. This approval letter must be dated and must clearly identify the IEC/IRB and the 
documents being approved.
During the study the investigator (or sponsor where required) will send the following documents 
and updates to the IEC/IRB for their review and approval, where appropriate:

Protocol amendments (excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct)

Revision(s) to ICF and any other written materials to be provided to subjects

If applicable, new or revised subject recruiting materials approved by the sponsor

Revisions to compensation for study-related injuries or payment to subjects for participation 
in the study, if applicable

New edition(s) of the Investigator's Brochure and amendments/addenda

Summaries of the status of the 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
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
Deviations from or changes to the protocol to eliminate immediate hazards to the subjects

Report of deaths of subjects under the investigator's care

Notification if a new investigator is responsible for the study at the site

Development Safety Update Report and Line Listings, where applicable

Any other requirements of the IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct), the amendment and applicable ICF revisions 
must be submitted promptly to the IEC/IRB for review and approval before implementation of 
the change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where 
required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB 
about the study completion.
16.2.3.
Informed Consent and Assent Form
Each subject (or a legally acceptable representative) must give written consent for the current 
study according to local requirements after the nature of the study has been fully explained. The 
ICF must be signed before performance of any study-related activity. The ICF and assent form 
that are used must be approved by both the sponsor and by the reviewing IEC/IRB and be in a 
language that the subject can read and understand. The informed consent should be in 
accordance with principles that originated in the Declaration of Helsinki, current ICH and GCP 
guidelines, applicable regulatory requirements, and sponsor policy.
Before enrollment in the study, the investigator or an authorized member of the study-site 
personnel must explain to potential subjects 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.
Subjects will be informed of the observational nature of the study, that the sponsor only intends 
to collect information and that their participation in the study does not involve invasive 
procedures. Only subjects who are fully able to understand the nature of the study and provide 
their consent voluntarily will be enrolled.
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.
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If the subject or legally acceptable representative is unable to read or write, an impartial witness 
should be present for the entire informed consent process (which includes reading and explaining 
all written information) and should personally date and sign the ICF after the oral consent of the 
subject or legally acceptable representative is obtained.
Children (minors) or subjects who are unable to comprehend the information provided can be 
enrolled only after obtaining consent of a legally acceptable representative. Assent must be 
obtained from children (minors) capable of understanding the nature of the study, typically 
subjects 7 years of age and older, depending on the institutional policies. Written assent should 
be obtained from subjects who are able to write. A separate assent form written in language the 
subject can understand should be developed for adolescents. After having obtained the assent, a 
copy of the assent form must be given to the subject, and to the subject's parent or legally 
acceptable representative, if applicable. Minors who assent to a study and later withdraw that 
assent should not be maintained in the study against their will, even if their parents still want them 
to participate.
For children participating in the study when referring to the signing of the participation 
agreement/ICF, the terms legal guardian and legally acceptable representative refer to the legally 
appointed guardian of the child with authority to authorize participation in research. For each 
subject, his/her parent(s) (preferably both parents, if available) or a legally acceptable 
representative(s), as required by local regulations, must give written consent (permission) 
according to local requirements after the nature of the study has been fully explained and before 
any data collection. 
Personal data collected from subjects enrolled in this study will be limited to those data that are 
necessary to fulfill the objectives of the study, and must be collected and processed with 
adequate precautions to ensure confidentiality and compliance with applicable data privacy 
protection laws and regulations (see Section 16.2.4).
16.2.4.
Privacy of Personal Data
The collection and processing of personal data from subjects enrolled in this study will be 
limited to those data that are necessary to fulfill the objectives of the study.
These data must be collected and processed with adequate precautions to ensure confidentiality 
and compliance with applicable data privacy protection laws and regulations. Appropriate 
technical and organizational measures to protect the personal data against unauthorized 
disclosures or access, accidental or unlawful destruction, or accidental loss or alteration must be 
put in place. Sponsor personnel whose responsibilities require access to personal data agree to 
keep the identity of subjects confidential.
The informed consent obtained from the subject (or his or her legally acceptable representative)
includes explicit consent for the processing of personal data and for the investigator/institution to 
allow direct access to his or her original medical records (source data/documents) for study-
related monitoring, audit, IEC/IRB review, and regulatory inspection. This consent also 
addresses the transfer of the data to other entities and to other countries.
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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.
17.
ADMINISTRATIVE REQUIREMENTS
17.1.
Protocol Amendments
Neither the investigator nor the sponsor will modify this protocol without a formal amendment 
by the sponsor. All protocol amendments must be issued by the sponsor, and signed and dated by 
the investigator. Protocol amendments must not be implemented without prior IEC/IRB 
approval, or when the relevant competent authority has raised any grounds for non-acceptance, 
except when necessary to eliminate immediate hazards to the subjects, in which case the 
amendment must be promptly submitted to the IEC/IRB and relevant competent authority. 
Documentation of amendment approval by the investigator and IEC/IRB must be provided to the 
sponsor. When the change(s) involves only logistic or administrative aspects of the study, the 
IRB/IEC (where required) only needs to be notified.
During the course of the study, in situations where a departure from the protocol is unavoidable, 
the investigator or other physician in attendance will contact the appropriate sponsor
representative (listed in the Contact Information page(s), which will be provided as a separate 
document). Except in emergency situations, this contact should be made before implementing 
any departure from the protocol. In all cases, contact with the sponsor must be made as soon as 
possible to discuss the situation and agree on an appropriate course of action. The data recorded 
in the CRF and source documents will reflect any departure from the protocol, and the source 
documents will describe this departure and the circumstances requiring it.
17.2.
Regulatory Documentation
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 drug to the 
study site:

Protocol and amendment(s), if any, signed and dated by the principal investigator

A copy of the dated and signed (or sealed, where appropriate per local regulations), written 
IEC/IRB approval of the protocol, amendments, ICF, any recruiting materials, and if 
applicable, subject compensation programs. This approval must clearly identify the specific 
protocol by title and number and must be signed (or sealed, where appropriate per local 
regulations) by the chairman or authorized designee.
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VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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
Name and address of the IEC/IRB, including a current list of the IEC/IRB members and 
their function, with a statement that it is organized and operates according to GCP and the 
applicable laws and regulations. If accompanied by a letter of explanation, or equivalent, 
from the IEC/IRB, a general statement may be substituted for this list. If an investigator or a 
member of the study-site personnel is a member of the IEC/IRB, documentation must be 
obtained to state that this person did not participate in the deliberations or in the 
vote/opinion of the study.

Regulatory authority approval or notification, if applicable

Signed and dated statement of investigator (eg, Form FDA 1572), if applicable

Documentation of investigator qualifications (eg, curriculum vitae)

Completed investigator financial disclosure form from the principal investigator, where 
required

Signed and dated clinical trial agreement, which includes the financial agreement

Any other documentation required by local regulations
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 study contacts; record of all serious adverse events and follow-
up of serious adverse events; record and follow-up of pregnancy; medication taken within a 
period of 30 days prior to the onset of a serious adverse event and up to the resolution of the 
serious adverse event, and date of study completion and reason for withdrawal from the study, if 
applicable.
The author of an entry in the source documents should be identifiable.
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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).
For children in Cohort 3, the following data will be recorded directly into the CRF and will be 
considered source data:

Race

Height, weight and growth percentiles at birth
For other cohorts, data will be copied from the analysis data set of the subject’s original study.
17.5.
Case Report Form Completion
CRFs are prepared and provided by the sponsor for each subject in electronic format. All data 
relating to the study must be recorded in CRF. 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 within the timeframe agreed upon between the sponsor and the study site. The electronic 
file will be considered to be the CRF.
Worksheets may be used for the capture of some data to facilitate completion of the CRF. Any 
such worksheets will become part of the subject's source documentation. All data relating to the 
study must be recorded in CRFs prepared by the sponsor. Data must be entered into CRFs in 
English. 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.
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VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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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 and/or 
remote monitoring by the sponsor. Written instructions will be provided for collection, handling, 
storage, and shipment of samples.
Guidelines for CRF completion will be provided and reviewed with study-site personnel before 
the start of the study. The sponsor will review CRFs for accuracy and completeness during on-
site monitoring visits and after their return/transmission to the sponsor; any discrepancies will be 
resolved with the investigator or designee, as appropriate. The data will be entered into the study
database and verified for accuracy and consistency with the data sources.
The investigator/institution will maintain all CRFs and source documentation that support the 
data collected for each subject, as well as all study documents specified by the applicable 
regulatory requirement(s) (see Section 17.2). The investigator/institution will take measures to 
prevent accidental or premature destruction of these documents. Essential documents must be 
retained for at least 5 years or other appropriate period as defined by local regulations after the 
completion of the final study report, but will be retained for a longer period if required by 
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. Further details of record retention policies are provided in Section 17.7.
Representatives of the sponsor may visit the participating site at any time during or after 
completion of the study to conduct an audit of the study in compliance with regulatory guidelines 
and/or company policy. Similar procedures may also be conducted by a regulatory body. Further 
details of on-site audit policies are presented in Section 17.10.
17.7.
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all CRFs 
and all source documents that support the data collected from each subject, as well as all study 
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a 
Clinical Trial, and all study documents as specified by the applicable regulatory requirement(s). 
The investigator/institution will take measures to prevent accidental or premature destruction of 
these documents.
Essential documents must be retained until at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. These documents will be 
retained for a longer period if required by the applicable regulatory requirements or by an 
agreement with the sponsor. It is the responsibility of the sponsor to inform the 
investigator/institution as to when these documents no longer need to be retained.
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If the responsible investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who will 
accept the responsibility. The sponsor must be notified in writing of the name and address of the 
new custodian. Under no circumstance shall the investigator relocate or dispose of any study 
documents before having obtained written approval from the sponsor.
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any 
documentation relating to this study, the investigator/institution must permit access to such 
reports.
17.8.
Monitoring
The sponsor will perform on-site monitoring visits. The monitor will record dates of the visits in 
a study site visit log that will be kept at the study site. 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, documentation of telephone calls with the subject). 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.
17.9.
Study Completion/End of Study
17.9.1.
Study Completion
The study is considered completed with the last data collection time point 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 data collection time point at that study site, in the time 
frame specified in the Clinical Trial Agreement.
17.9.2.
Study Termination
The sponsor reserves the right to close the study site for data collection 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.
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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
The investigator should immediately notify the sponsor if they have been contacted by a 
regulatory agency concerning an upcoming inspection.
17.10. On-Site Audits
Representatives of the sponsor's clinical quality assurance department may visit the study site at 
any time during or after completion of the study to conduct an audit of the study in compliance 
with regulatory guidelines and company policy. These audits will require access to all study 
records, including source documents, for inspection. Subject privacy must, however, be 
respected. The investigator and study-site personnel are responsible for being present and 
available for consultation during routinely scheduled study-site audit visits conducted by the 
sponsor or its designees.
Similar auditing procedures may also be conducted by agents of any regulatory body, either as 
part of a national GCP compliance program or to review the results of this study in support of a 
regulatory submission. The investigator should immediately notify the sponsor if he or she has
been contacted by a regulatory agency concerning an upcoming inspection.
17.11. Use of Information and Publication
All information, including but not limited to information regarding Ad6.ZEBOV and MVA-BN-
Filo (VAC52150) 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 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 Ad6.ZEBOV and MVA-BN-Filo
(VAC52150), and thus may be disclosed as required to other clinical investigators or regulatory 
agencies. To permit the information derived from the clinical studies to be used, the investigator 
is obligated to provide the sponsor with all data obtained in the study.
The results of the study will be reported in a Clinical Study Report generated by the sponsor and 
will contain CRF data from all study sites that participated in the study.
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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. Study subject 
identifiers will not be used in publication of results. Any work created in connection with 
performance of the study and contained in the data that can benefit from copyright protection 
(except any publication by the investigator as provided for below) shall be the property of the 
sponsor as author and owner of copyright in such work.
Consistent with Good Publication Practices and International Committee of Medical Journal 
Editors guidelines, the sponsor shall have the right to publish such primary (multicenter) data 
and information without approval from the investigator. The investigator has the right to publish 
study site-specific data after the primary data are published. If an investigator wishes to publish 
information from the study, a copy of the manuscript must be provided to the sponsor for review 
at least 60 days before submission for publication or presentation. Expedited reviews will be 
arranged for abstracts, poster presentations, or other materials. If requested by the sponsor in 
writing, the investigator will withhold such publication for up to an additional 60 days to allow 
for filing of a patent application. In the event that issues arise regarding scientific integrity or 
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, graphs), or the sponsor confirms there will be no multicenter study publication. 
Authorship of publications resulting from this study will be based on the guidelines on 
authorship, such as those described in the Uniform Requirements for Manuscripts Submitted to 
Biomedical Journals, which state that the named authors must have made a significant 
contribution to the design of the study or analysis and interpretation of the data, provided critical 
review of the paper, and given final approval of the final version.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and disclose the existence of and the results of clinical studies as 
required by law.
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VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B])
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REFERENCES
1.
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).
2.
Clinical Study Report VAC52150EBL1001 (Primary Analysis). A Phase 1, first-in-human study to evaluate 
the safety, tolerability and immunogenicity of heterologous prime-boost regimens using MVA-BN-Filo and 
A26.ZEBOV administered in different sequences and schedules in healthy adults. Crucell Holland B.V. (Oct
2015).
3.
Friedrich B, Trefry J, Biggins J, et al. Potential vaccines and post-exposure treatments for filovirus infections. 
Viruses. 2012;4(9):1619-1650.
4.
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 19 November 2015.
5.
Investigator’s Brochure: JNJ-61210474 (Ad26.ZEBOV), Edition 3. Crucell Holland B.V. (Oct 2015). For 
updated information, refer to Edition 4 (Janssen Vaccines & Prevention, 23 June 2016).
6.
Investigator’s Brochure: MVA-BN-Filo (MVA-mBN226B), Edition 6. Bavarian Nordic A/S (Nov 2015). For 
updated information, refer to Edition 10 (11 July 2016).
7.
MVA-BN® (Modified Vaccinia Ankara - Bavarian Nordic). Available at: http://id.bavarian-
nordic.com/pipeline/technology-platform/mva-bn.aspx Accessed 19 November 2015.
8.
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.
9.
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.
10.
WHO Fact Sheet No103 Ebola Virus Disease 2014. Available at: 
http://www.who.int/mediacentre/factsheets/fs103/en/. Accessed 19 November 2015.
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INVESTIGATOR AGREEMENT
I have read this protocol and agree that it contains all necessary details for carrying out this study. I will 
conduct the study as outlined herein and will complete the study within the time designated.
I will provide copies of the protocol and all pertinent information to all individuals responsible to me who 
assist in the conduct of this study. I will discuss this material with them to ensure that they are fully 
informed regarding the study drug, the conduct of the study, and the obligations of confidentiality.
Coordinating Investigator (where required):
Name (typed or printed):
Institution and Address:
Signature:
Date:
(Day Month Year)
Principal (Site) Investigator:
Name (typed or printed):
Institution and Address:
Telephone Number:
Signature:
Date:
(Day Month Year)
Sponsor's Responsible Medical Officer:
Name (typed or printed):
Institution:
Janssen Vaccines & Prevention B.V.
Signature:
electronic signature appended at the end of the protocol
Date:
(Day Month Year)
Note: If the address or telephone number of the investigator changes during the course of the study, written 
notification will be provided by the investigator to the sponsor, and a protocol amendment will not be required.
LAST PAGE
PPD
NCT02661464

 
 
SIGNATURES 
 
 
 
 
Signed by  
Date  
 
Justification  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
02Mar2017, 14:02:27 PM, UTC
Document Approval
PPD
NCT02661464