A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Immunogenicity, Safety, Reactogenicity, and Consistency of a Heterologous 2-dose Vaccine Regimen Using 3 Consecutive Lots of Ad26.ZEBOV and MVA-BN®-Filo in Adult Participants
Phase: PHASE3
Conditions: Ebola
Sponsor: Janssen Vaccines & Prevention B.V.

CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 15 June 2020
Janssen Vaccines & Prevention B.V. *
Clinical Protocol
A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the 
Immunogenicity, Safety, Reactogenicity, and Consistency of a Heterologous 2-dose Vaccine
Regimen Using 3 Consecutive Lots of Ad26.ZEBOV and MVA-BN®-Filo in Adult 
Participants.
Protocol VAC52150EBL3004; Phase 3
AMENDMENT 3
VAC52150 (Ad26.ZEBOV, MVA-BN-Filo [mBN226B])
*Janssen Vaccines & Prevention 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.
US sites of this study will be conducted under US Food & Drug Administration IND regulations 
(21 CFR Part 312).
Status:
Approved
Date:
15 June 2020
Prepared by:
Janssen Vaccines & Prevention B.V.
EDMS number:
EDMS-ERI-175180243, 10.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements. 
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that the Company 
customarily holds close and treats as confidential. The information is being provided under the assurance that the recipient 
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or 
otherwise.
NCT04228783

VAC52150 (Ad26.ZEBOV, MVA-BN-Filo [mBN226B])
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TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF ATTACHMENTS............................................................................................................................ 4
LIST OF IN-TEXT TABLES.......................................................................................................................... 4
PROTOCOL AMENDMENTS....................................................................................................................... 5
SYNOPSIS.................................................................................................................................................. 11
TIME AND EVENTS SCHEDULE .............................................................................................................. 18
ABBREVIATIONS ...................................................................................................................................... 23
DEFINITIONS OF TERMS.......................................................................................................................... 24
1.
INTRODUCTION................................................................................................................................ 25
1.1.
Background .................................................................................................................................... 25
1.2.
Benefit/Risk Section....................................................................................................................... 28
1.2.1.
Known Benefits........................................................................................................................... 28
1.2.2.
Potential Benefits........................................................................................................................ 28
1.2.3.
Known Risks............................................................................................................................... 28
1.2.4.
Potential Risks............................................................................................................................ 28
1.2.5.
Overall Benefit/Risk Assessment ............................................................................................... 30
1.3.
Overall Rationale for the Study...................................................................................................... 30
2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESES.......................................................................... 31
2.1.
Objectives and Endpoints .............................................................................................................. 31
2.2.
Hypotheses .................................................................................................................................... 32
2.2.1.
Primary Hypotheses ................................................................................................................... 32
2.2.2.
Secondary Hypotheses............................................................................................................... 33
3.
STUDY DESIGN AND RATIONALE ................................................................................................. 33
3.1.
Overview of Study Design.............................................................................................................. 33
3.2.
Study Design Rationale.................................................................................................................. 37
4.
PARTICIPANT POPULATION .......................................................................................................... 37
4.1.
Inclusion Criteria ............................................................................................................................ 37
4.2.
Exclusion Criteria ........................................................................................................................... 39
4.3.
Prohibitions and Restrictions ......................................................................................................... 41
5.
STUDY VACCINE ALLOCATION AND BLINDING.......................................................................... 41
6.
DOSAGE AND ADMINISTRATION .................................................................................................. 43
6.1.
Criteria for Postponement of Vaccination ...................................................................................... 44
6.2.
Contraindications to Second Vaccination ...................................................................................... 44
7.
STUDY VACCINE COMPLIANCE .................................................................................................... 44
8.
PRESTUDY AND CONCOMITANT THERAPY ................................................................................ 44
9.
STUDY EVALUATIONS .................................................................................................................... 45
9.1.
Study Procedures........................................................................................................................... 45
9.1.1.
Overview..................................................................................................................................... 45
9.1.2.
Screening, Vaccination, Postvaccination Visits, and Follow-up ................................................. 46
9.2.
Immunogenicity Evaluations .......................................................................................................... 47
9.3.
Safety Evaluations ......................................................................................................................... 48

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9.3.1.
Safety Assessments ................................................................................................................... 48
9.3.2.
Study Vaccination Pausing Rules............................................................................................... 50
9.4.
Sample Collection and Handling.................................................................................................... 51
10.
PARTICIPANT COMPLETION/DISCONTINUATION OF STUDY VACCINE/ 
WITHDRAWAL FROM THE STUDY................................................................................................. 51
10.1.
Completion ..................................................................................................................................... 51
10.2.
Discontinuation of Study Vaccine/Withdrawal From the Study...................................................... 51
11.
STATISTICAL METHODS................................................................................................................. 52
11.1.
Analysis Sets.................................................................................................................................. 53
11.2.
Sample Size Determination ........................................................................................................... 54
11.3.
Immunogenicity Analyses .............................................................................................................. 55
11.4.
Safety Analysis............................................................................................................................... 56
12.
ADVERSE EVENT REPORTING ...................................................................................................... 57
12.1.
Definitions ...................................................................................................................................... 57
12.1.1.
Adverse Event Definitions and Classifications ........................................................................... 57
12.1.2.
Attribution Definitions.................................................................................................................. 58
12.1.3.
Severity Criteria .......................................................................................................................... 59
12.2.
Special Reporting Situations.......................................................................................................... 59
12.3.
Procedures..................................................................................................................................... 59
12.3.1.
All Adverse Events...................................................................................................................... 59
12.3.2.
Serious Adverse Events ............................................................................................................. 61
12.3.3.
Pregnancy................................................................................................................................... 62
12.4.
Contacting Sponsor Regarding Safety........................................................................................... 62
13.
PRODUCT QUALITY COMPLAINT HANDLING.............................................................................. 62
13.1.
Procedures..................................................................................................................................... 63
13.2.
Contacting Sponsor Regarding Product Quality ............................................................................ 63
14.
STUDY VACCINE INFORMATION ................................................................................................... 63
14.1.
Physical Description of Study Vaccines......................................................................................... 63
14.1.1.
Ad26.ZEBOV .............................................................................................................................. 63
14.1.2.
MVA-BN-Filo............................................................................................................................... 63
14.2.
Packaging ...................................................................................................................................... 63
14.3.
Labeling.......................................................................................................................................... 64
14.4.
Preparation, Handling, and Storage............................................................................................... 64
14.5.
Study Vaccine Accountability......................................................................................................... 64
15.
STUDY-SPECIFIC MATERIALS....................................................................................................... 65
16.
ETHICAL ASPECTS ......................................................................................................................... 65
16.1.
Study-specific Design Considerations ........................................................................................... 65
16.2.
Regulatory Ethics Compliance....................................................................................................... 66
16.2.1.
Investigator Responsibilities ....................................................................................................... 66
16.2.2.
Independent Ethics Committee or Institutional Review Board ................................................... 66
16.2.3.
Informed Consent ....................................................................................................................... 67
16.2.4.
Privacy of Personal Data ............................................................................................................ 68
16.2.5.
Long-term Retention of Samples for Additional Future Research.............................................. 69
17.
ADMINISTRATIVE REQUIREMENTS .............................................................................................. 69
17.1.
Protocol Amendments.................................................................................................................... 69
17.2.
Regulatory Documentation ............................................................................................................ 70
17.2.1.
Regulatory Approval/Notification ................................................................................................ 70
17.2.2.
Required Prestudy Documentation............................................................................................. 70
17.3.
Participant Identification, Enrollment, and Screening Logs ........................................................... 70
17.4.
Source Documentation................................................................................................................... 71
17.5.
Case Report Form Completion ...................................................................................................... 72

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17.6.
Data Quality Assurance/Quality Control ........................................................................................ 72
17.7.
Record Retention ........................................................................................................................... 73
17.8.
Monitoring ...................................................................................................................................... 73
17.9.
Study Completion/Termination....................................................................................................... 74
17.9.1.
Study Completion/End of Study.................................................................................................. 74
17.9.2.
Study Termination....................................................................................................................... 74
17.10.
On-site Audits................................................................................................................................. 74
17.11.
Use of Information and Publication................................................................................................ 75
REFERENCES............................................................................................................................................ 77
ATTACHMENTS......................................................................................................................................... 78
INVESTIGATOR AGREEMENT ................................................................................................................. 81
LIST OF ATTACHMENTS
Attachment 1: 
Toxicity Tables for Use in Studies Enrolling Healthy Adults.......................................... 78
LIST OF IN-TEXT TABLES 
Table 1:
Schematic Overview of Study Design and Groups................................................................... 35

VAC52150 (Ad26.ZEBOV, MVA-BN-Filo [mBN226B])
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Approved, Date: 15 June 2020
PROTOCOL AMENDMENTS
Protocol Version 
Date
Original Protocol
19 September 2019
Amendment 1
25 November 2019
Amendment 2
2 April 2020
Amendment 3
This document
Amendments below are listed beginning with the most recent amendment.
Amendment 3 (This document)
The overall reason for the amendment: This amendment responds to the impact of Coronavirus Disease 2019 
(COVID-19) on the ability of participants to return within window (±3 days) for Dose 2 in this lot-to-lot consistency 
study and proposes to widen the window, while maintaining the ability to achieve the primary and secondary 
objectives of the study.
Applicable Section(s)
Description of Change(s)
Rationale: Shortly after Dose 1 (Ad26.ZEBOV) was administered to the participants, ‘stay-at-home’ orders were 
imposed in the cities where the clinical sites are located. Although the sites were able to remain open with 
appropriate safety measures, a significant number of participants did not return within window for Dose 2 
(MVA-BN-Filo) vaccination. The failure-to-return rate was approximately 22% which would likely lead to 
underpowering for the primary objective. Protocol amendment 2 allows for replacement of subjects in the 
immunogenicity subset if the dropout rate exceeded 5% due to COVID-19 but did not widen the acceptable time 
frame to receive Dose 2 and still be able to contribute to the per protocol analysis. Analysis of the variability data 
of the ELISA assay remains stable when the interval between the 2 vaccines is widened from Day 56 out to Day 85 
(data from studies VAC52150EBL2001 and VAC52150EBL2002) and even remains stable when the interval is 
≥56 (data from the immunogenicity analysis set from study VAC52150EBL2002). It is noted that while the 
variability around the ELISA values remains stable, the GMCs increase modestly as the interval of time between 
doses increases. Because the assignment of the additional participants to the groups will be blinded and random, 
there should be no impact on our ability to demonstrate comparability between the groups. Given that the variability 
around the measurement remains stable, assignment to the groups will be random and in the absence of any safety 
concerns, this amendment will widen the acceptable time frame around Dose 2 to minimize the number of 
exclusions from the per protocol analysis and will apply to participants already vaccinated in the study.
Protocol amendment 2 provided for the recruitment of 2 additional Groups (5 and 6) who will receive a booster 
dose. These participants have not yet been recruited. It is expected that these additional groups will likely receive 
their second dose in the fall of 2020, at which time it is possible that a second wave of COVID-19 may occur. The 
window for Dose 2 for these groups, therefore, is only being increased to 1 week to try to assure that Dose 2 is 
completed before a recurrence of COVID-19. 
Furthermore, the window for Dose 2 for Groups 5 and 6 is limited to 1 week since this extension for the window 
is deemed suitable for the correct interpretation of the anamnestic response to the booster dose. If the window for 
Dose 2 is further extended such that the time between Dose 2 and the booster dose is decreased, the primary 
response to the initial 2-dose regimen may not have reached a plateau at the time the booster dose is given and the 
immune system may be differently susceptible to the booster.
SYNOPSIS
TIME AND EVENTS SCHEDULE
ABBREVIATIONS
3.1 Overview of Study Design
11.2 Sample Size Determination
11.3 Immunogenicity Analyses
Clarified the change in visit window around Dose 2 for all 
groups.
Increasing the window around Dose 2 for Groups 1-4.
Increasing the window around Dose 2 for Groups 5 and 6.
Provided rationale supporting the increase in visit window 
around Dose 2 while preserving the ability to achieve the 
primary and secondary objectives.
As a sensitivity analyses, both the primary and secondary 
hypotheses of equivalence will also be tested based on data 
of participants who received the second vaccination within 
the original window (±3 days) around the Day 57 visit.

VAC52150 (Ad26.ZEBOV, MVA-BN-Filo [mBN226B])
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Applicable Section(s)
Description of Change(s)
Rationale: In line with the current protocol template, the Confidentiality Statement on the title page was updated
and a footer was added.
Throughout the document.

VAC52150 (Ad26.ZEBOV, MVA-BN-Filo [mBN226B])
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Approved, Date: 15 June 2020
Amendment 2 (2 April 2020)
The overall reason for the amendment: This amendment is written to accommodate a request from EMA to 
obtain safety and immunogenicity data of a booster dose of Ad26.ZEBOV given 4 months after the primary 
vaccine regimen.
Applicable Section(s)
Description of Change(s)
Rationale: Administration of a booster dose of Ad26.ZEBOV given at 1- and 2 years post Dose 1 in studies 
VAC52150EBL1002, VAC52150EBL2002 and VAC52150EBL3001 induced a rapid and robust anamnestic 
response to the booster vaccine. Administration of a booster dose in anticipation of imminent exposure to Ebola 
(ie, prior to deployment to an Ebola outbreak area) may be desired as a precautionary measure to optimize 
protection. However, there are currently no clinical data available on the immunogenicity and safety of such an 
Ad26.ZEBOV booster dose when administered less than 1 year after the primary vaccine regimen. Booster doses 
as early as 2-3 months after Dose 2 were assessed in a multivalent filovirus and an HIV vaccine program and were 
able to induce a marked increase in antibody concentrations, although to a lower magnitude than a later booster. 
Furthermore, based on the kinetics of decrease in antibody concentrations after the Ad26.ZEBOV, MVA-BN-Filo 
vaccine regimen, supported by a mechanistic model of antibody persistence and general vaccine knowledge, an 
Ad26.ZEBOV booster dose administered from 4 months after completion of the primary vaccine regimen is likely 
to induce a strong anamnestic response based on mature immune memory and to maximize the likelihood of 
protection in case of imminent risk of exposure to Ebola. Therefore, a separate Booster Cohort of participants will 
receive the primary vaccine regimen followed by a booster dose of Ad26.ZEBOV 4 months after Dose 2. The 
participants in this Booster Cohort will be assessed for safety and immunogenicity.
SYNOPSIS
TIME AND EVENTS SCHEDULE
1.2.4 Potential Risks
1.2.5 Overall Benefit/Risk Assessment
1.3 Overall Rationale for the Study
2.1 Objectives and Endpoints
3.1 Overview of Study Design
3.2 Study Design Rationale
4.1 Inclusion Criteria
4.2 Exclusion Criteria
4.3 Prohibitions and Restrictions
5 STUDY VACCINE ALLOCATION AND 
BLINDING
6 DOSAGE AND ADMINISTRATION
6.1 Criteria for Postponement of Vaccination
6.2 Contraindications to Second Vaccination
8 PRESTUDY AND CONCOMITANT THERAPY
9.1.1 Overview
9.1.2 Screening, Vaccination, Postvaccination Visits, 
and Follow-up
9.2 Immunogenicity Evaluations
9.3.1 Safety Assessments
10.1 Completion
10.2 Discontinuation of Study Vaccine/Withdrawal 
From the Study
11 STATISTICAL METHODS
11.1 Analysis Sets
11.2 Sample Size Determination
11.4 Safety Analysis
12.3.1 All Adverse Events
17.4 Source Documentation
An additional cohort of 60 participants will be enrolled 
in a 5:1 active:placebo ratio. The participants will be
given the 2-dose heterologous vaccine regimen, 
Ad26.ZEBOV followed by MVA-BN-Filo 56 days 
later, and a booster dose of Ad26.ZEBOV 4 months 
after Dose 2, or placebo.
To all sections listed in the 1st column, details for the 
Booster Cohort were added.

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Applicable Section(s)
Description of Change(s)
Rationale: Due to the recent (on 11 March 2020) WHO-declared COVID-19 pandemic, the following issues may 
occur:
A potential higher dropout rate (ie, higher than 5%) may occur and/or some participants in the 
immunogenicity subset may be excluded from primary immunogenicity equivalence testing (Dose 2 not 
received or received out of window, no attendance or out of window attendance of the 21-day post Dose 2 
visit). To mitigate these issues, additional participants may be recruited in the immunogenicity subset.
It may become difficult to conduct study visits on site. Therefore, alternative arrangements to conduct study 
visits according to the protocol may be considered.
SYNOPSIS
3.1 Overview of Study Design
11.2 Sample Size Determination
Addition of language regarding extra recruitment in the 
immunogenicity subset due to issues caused by the 
COVID-19 pandemic.
TIME AND EVENTS SCHEDULE
Addition of a sentence allowing for alternative 
arrangements to conduct study visits according to the 
protocol.
Rationale: In some study participants, missing data were noted due to difficulties in obtaining a blood sample. To 
avoid this in the future, participants for which it is difficult to obtain blood draws, will be excluded from the study.
4.2 Exclusion Criteria
Addition of an exclusion criterion specifying that 
participants for which it is difficult to take a blood
sample will not be allowed to enter the study.
Rationale: Minor changes were made throughout the document. 
DEFINITIONS OF TERMS
Addition of the definition of immunogenicity subset for 
clarity.
1.3 Overall Rationale for the Study
Addition of generic terminology with regards to 
approval of the vaccine regimen by a regulatory 
authority.
11.1 Analysis Sets
Replacement of the term protocol violations by protocol 
deviations.
Attachment 1
Correction of the originating DMID toxicity table 
version (2014 to 2007).
TIME AND EVENTS SCHEDULE
Minor editorial changes.

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Approved, Date: 15 June 2020
Amendment 1 (25 November 2019)
The overall reason for the amendment: This amendment is written in response to the questions received from 
FDA on 8 November 2019.
Applicable Section(s)
Description of Change(s)
Rationale: The protocol was updated to exclude breast-feeding women as the study is not designed to assess the 
safety of the vaccine regimen in lactating women.
4.2 Exclusion Criteria
Exclusion of breast-feeding women as the study is not designed to assess the safety of 
the vaccine regimen in lactating women.
Rationale: The protocol was updated to add a telephone call between the study participant and the study site 
personnel for safety purposes at Day 29 (28 days post Dose 1) to promote recall of unsolicited adverse events 
experienced by study participants. Furthermore, procedures for safety evaluation were further clarified in the 
protocol.
SYNOPSIS, TIME 
AND EVENTS 
SCHEDULE, 3.1
Overview of Study 
Design, 9.1.2
Screening, 
Vaccination, 
Postvaccination Visits, 
and Follow-up
Addition of a telephone call between the study participant and the study site personnel 
for safety purposes at Day 29 (28 days post Dose 1) to promote recall of unsolicited 
adverse events experienced by study participants.
9.3 Safety Evaluations
Clarification was added on the procedures used for safety evaluation.
SYNOPSIS, 1.2.5
Overall Benefit/Risk 
Assessment, 3.1
Overview of Study 
Design, 9.3 Safety 
Evaluations
Study vaccination pausing rules were added.
Rationale: The protocol was updated to exclude participants with any clinically significant acute or chronic 
medical condition that in the opinion of the investigator would preclude participation.
4.2 Exclusion Criteria
Exclusion of participants with any clinically significant acute or chronic medical 
condition that in the opinion of the investigator would preclude participation.

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Applicable Section(s)
Description of Change(s)
Rationale: It was clarified in the protocol that all sponsor personnel involved in the determination of the 
causality for serious adverse events reported during the study are to remain blinded to vaccine allocation. 
Furthermore, clarification was added in the protocol for maintaining the study blind and ensuring that 
non-sponsor study site personnel will not be inadvertently exposed to unblinded data.
SYNOPSIS, 3.1
Overview of Study 
Design, 5 STUDY 
VACCINE 
ALLOCATION AND 
BLINDING, 
11 STATISTICAL 
METHODS
Clarification was added that all sponsor personnel involved in the determination of the 
causality for serious adverse events reported during the study are to remain blinded to 
vaccine allocation until final database lock.
5 STUDY VACCINE 
ALLOCATION AND 
BLINDING
Clarification was added for maintaining the study blind and ensuring that non-sponsor 
study site personnel will not be inadvertently exposed to unblinded data.
Rationale: Minor errors were noted.
SYNOPSIS, 3.1
Overview of Study 
Design, 4.2 Exclusion 
Criteria
MVA-BN-Filo is contraindicated in individuals with hypersensitivity to the active 
substance in MVA-BN-Filo or to any of its excipients, or trace residues (chicken or 
egg protein and gentamicin). The protocol has been updated accordingly.
Throughout the 
protocol
Minor changes in abbreviation use were made.

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SYNOPSIS
A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Immunogenicity, Safety, 
Reactogenicity, and Consistency of a Heterologous 2-dose Vaccine Regimen Using 3 Consecutive Lots of 
Ad26.ZEBOV and MVA-BN®-Filo in Adult Participants.
Janssen Vaccines & Prevention B.V. (hereafter referred to as the sponsor), in collaboration with Bavarian 
Nordic GmbH (BN) is developing a prophylactic Ebola vaccine regimen (VAC52150) comprised of the 
following 2 candidate Ebola vaccines:
Ad26.ZEBOV is a monovalent vaccine expressing the full-length glycoprotein (GP) of the Ebola virus 
(EBOV, formerly known as Zaire ebolavirus) Mayinga variant. The vaccine 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 EBOV Mayinga GP, the Sudan virus (SUDV) GP, the Marburg virus (MARV) 
Musoke GP, and the Tai Forest virus (TAFV, formerly known as Côte d’Ivoire ebolavirus) nucleoprotein 
(NP). The EBOV GP expressed by MVA-BN-Filo has 100% homology with the one expressed by 
Ad26.ZEBOV.
OBJECTIVES, ENDPOINTS, AND HYPOTHESES
Objectives
Endpoints
Primary

To demonstrate that the paired 2-dose vaccine
regimens from 3 consecutively manufactured 
lots of Ad26.ZEBOV as Dose 1
and 
3 consecutively 
manufactured
lots 
of 
MVN-BN-Filo as Dose 2, administered at a 
56-day 
interval,
induce 
an 
equivalent 
humoral immune response.

Binding antibody levels against the EBOV GP 
using enzyme-linked immunosorbent assay 
(ELISA, ELISA units/mL [EU/mL]) at 21 days 
post Dose 2 vaccination.
Secondary

To 
demonstrate 
that 
3 
consecutively 
manufactured
lots of Ad26.ZEBOV as 
Dose 1
induce an equivalent humoral 
immune response.

Binding antibody levels against the EBOV GP 
using ELISA (EU/mL) at 56 days post Dose 1
vaccination.

To assess the safety and reactogenicity of a 
heterologous 2-dose vaccine regimen of 
Ad26.ZEBOV 
and 
MVA-BN-Filo 
administered intramuscularly (IM) on Days 1 
and 57, respectively, using 3 different lots of 
Ad26.ZEBOV 
and 
3 different 
lots 
of 
MVA-BN-Filo.

Solicited local and systemic adverse events until 
7 days post each vaccination.

Unsolicited adverse events until 28 days post
each vaccination.

Serious adverse events until the end of the study.
Exploratory (Booster Cohort only)

To assess the humoral immune response to a 
booster 
dose 
of 
Ad26.ZEBOV 
given 
4 months after Dose 2 

Binding antibody levels against the EBOV GP 
using ELISA (EU/mL) at pre booster (Day 177) 
and several post booster timepoints (7-days, 
21-days, 6-months and 12-months post booster 
dose)

VAC52150 (Ad26.ZEBOV, MVA-BN-Filo [mBN226B])
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Objectives
Endpoints

To assess the safety and reactogenicity of a 
booster dose of Ad26.ZEBOV 

Solicited local and systemic adverse events until 
7 days post booster vaccination.

Unsolicited adverse events until 28 days post 
booster vaccination.

Serious adverse events until the end of the study.

To assess the presence of neutralizing 
antibodies against the Ad26 vector

Viral neutralizing antibody levels against the 
Ad26 vector at baseline, pre booster vaccination
(Day 177), and at 21 days post booster 
vaccination.
Hypotheses
The primary hypotheses are:
Null hypothesis: 
Three consecutive lots of Ad26.ZEBOV (Lots A, B, and C) as Dose 1 paired sequentially in 3 groups with
3 consecutive lots of MVA-BN-Filo (Lots 1, 2, and 3) as Dose 2 do not induce equivalent geometric mean 
concentrations (GMCs) of the EBOV GP-specific antibody response 21 days post Dose 2, for at least one 
pairwise comparison.
Alternative hypothesis: 
Three consecutive lots of Ad26.ZEBOV (Lots A, B, and C) as Dose 1 paired sequentially in 3 groups with
3 consecutive lots of MVA-BN-Filo (Lots 1, 2, and 3) as Dose 2 induce equivalent GMCs of the EBOV 
GP-specific antibody response 21 days post Dose 2, for all 3 pairwise comparisons (ie, Groups 1 versus 
[vs] 2, 1 vs 3 and 2 vs 3).
Equivalence of any 2 groups (Ad26.ZEBOV as Dose 1 followed by MVA-BN-Filo as Dose 2) will be 
shown if the 95% confidence interval [CI] of the estimated GMC ratio lies entirely within 0.5 and 2.0. 
These equivalence limits were chosen primarily based on the population variability as measured by the 
ELISA assay. Immunogenic equivalence of the 3 different lots of Ad26.ZEBOV (Lots A, B, and C) paired 
sequentially in 3 groups with 3 different lots of MVA-BN-Filo (Lots 1, 2, and 3) is established if 
equivalence is shown for all 3 pairwise comparisons.
The secondary hypotheses will be tested on the EBOV GP-specific antibody response 56 days post Dose 1. 
Similar null and alternative hypotheses will be formulated and tested using the same criteria outlined for 
the primary hypotheses.
OVERVIEW OF STUDY DESIGN
This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter, Phase 3 study to
evaluate lot-to-lot consistency of the manufacturing process by assessing the immunogenicity of the final 
product of 3 consecutively manufactured lots of Ad26.ZEBOV at a nominal dose of 5x1010 viral 
particles (vp) as Dose 1 and 3 consecutively manufactured lots of MVA-BN-Filo at a nominal dose of 1x108
infectious units (Inf U) as Dose 2 at a 56-day interval in adult participants (Groups 1-4). Once 
randomization of this part of the study is finished, an additional Booster Cohort of 60 participants will be 
enrolled in a 5:1 active:placebo ratio. These participants will be given the 2-dose heterologous vaccine 
regimen Ad26.ZEBOV followed by MVA-BN-Filo 56 days later, and a booster dose of Ad26.ZEBOV
4 months after Dose 2, or placebo (Groups 5-6).

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The 3 consecutive Ad26.ZEBOV drug product lots that will be used in the study have been manufactured
at the final manufacturing site (ie, IDT Biologika GmbH in Dessau-Rosslau, Germany [IDT]) and are 
representative of the final manufacturing process and scale (Lots A, B, and C). The 3 consecutive 
MVA-BN-Filo drug product lots that will be used have been manufactured at the final manufacturing site 
(IDT) and are representative of the final manufacturing process and scale (Lots 1, 2, and 3). Lots A, B, and 
C and Lots 1, 2, and 3 are paired sequentially in 3 groups (ie, A:1 [Group 1], B:2 [Group 2], and C:3 
[group 3]). Group 4 will receive 2 placebo vaccinations.
In the main part of the study (Groups 1-4), a planned total number of at least 741 participants will be 
enrolled. All participants in this part of the study will be assessed for safety and reactogenicity; 
456 participants (144 in each of Groups 1 to 3 and 24 in Group 4) will also be assessed for immunogenicity 
(immunogenicity subset). Participants will be randomly assigned to one of 4 groups in a 6:6:6:1 ratio, ie, to 
one of the 3 groups receiving Ad26.ZEBOV and MVA-BN-Filo (Groups 1 to 3) with a total of at least 
234 participants per group, or to a placebo group (Group 4) with 39 participants, and the first 
456 participants belonging to the immunogenicity subset.
Due to the recent (on 11 March 2020) WHO declared COVID-19 pandemic, a potential higher dropout rate 
(ie, higher than 5%) may occur. In addition, some participants in the immunogenicity subset may be 
excluded from primary immunogenicity equivalence testing because of:

Participant not receiving Dose 2; OR

Participant receiving Dose 2 outside the protocol defined window; OR

Participant not attending the 21-day post Dose 2 visit; OR

Participant attending the 21-day post Dose 2 visit outside the protocol-defined window.
To mitigate these issues, additional participants may be recruited in the immunogenicity subset.
Shortly after participants received Dose 1 vaccination, ‘stay-at-home’ orders were imposed in the areas 
where the sites were located. Although the sites had implemented appropriate safety measures to prevent 
spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), approximately 22% of 
participants did not return to the site within the protocol defined windows (±3 days) for Dose 2 
administration. Investigators were instructed to bring participants back to the site to complete the vaccine 
regimen, even if they were out of window. Currently, the stay-at-home orders have been lifted and 
participants are now able to return to the sites for follow-up. In order to reduce the number of additional 
participants needed for the primary and secondary immunogenicity analyses, it is possible to widen the 
acceptable window around Dose 2 administration without jeopardizing the primary and secondary 
objectives of the study. The protocol has been amended to widen the upper limit of the window around 
Day 57 (Dose 2) to Day 85 (ie, Day 57+28 days). Therefore, the number of additional participants necessary 
for inclusion in the immunogenicity subset and who would receive their second vaccination within the 
Day 57 window will be reduced.
For the Booster Cohort (Groups 5-6), a planned total of 60 participants will be enrolled. All participants in 
this cohort will be assessed for safety, reactogenicity, and immunogenicity. Participants will be randomly 
assigned to the 2 groups in a 5:1 ratio, ie, to a group of approximately 50 participants receiving the primary 
vaccine regimen (Ad26.ZEBOV followed by MVA-BN-Filo 56 days later) followed by a booster dose of 
Ad26.ZEBOV 4 months after Dose 2 (Group 5), or, to a placebo group of approximately 10 participants
(Group 6).
These 2 additional Groups (5 and 6) have not yet been recruited. It is expected that these additional groups 
will likely receive their second dose in the fall of 2020, at which time it is possible that a second wave of 
COVID-19 may occur. The window for Dose 2 for these groups, therefore, is only being increased to 1 week 
to try to assure that Dose 2 is completed before a recurrence of COVID-19. 
Furthermore, the window for Dose 2 for Groups 5 and 6 is limited to 1 week since this extension for the 
window is deemed suitable for the correct interpretation of the anamnestic response to the booster dose. If 

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the window for Dose 2 is further extended such that the time between Dose 2 and the booster dose is 
decreased, the primary response to the initial 2-dose regimen may not have reached a plateau at the time 
the booster dose is given and the immune system may be differently susceptible to the booster.
The participants will be randomized at baseline (Day 1) to receive the 2-dose vaccine regimen with either 
Ad26.ZEBOV and MVA-BN-Filo, or placebo. Randomization of the Booster Cohort (Groups 5-6) will take 
place once randomization of the main part of the study (Groups 1-4) has been completed. Randomization
will be done by the interactive web response system (IWRS). For Groups 1-4, investigators, study site 
personnel (except for those with primary responsibility for study vaccine preparation and dispensing), and 
participants will be blinded to the study vaccine allocation until the last participant in these groups
completes the 6-month post Dose 2 time point (ie, Day 237) or discontinues earlier (and the database is 
locked). For Groups 5-6, investigators, study site personnel (except for those with primary responsibility 
for study vaccine preparation and dispensing), and participants will be blinded to the study vaccine
allocation until the end of the study. Only sponsor personnel not involved in the review and determination 
of causality of serious adverse events reported during the study will be unblinded for Groups 1-4 at the time 
of the primary safety and immunogenicity analyses (28 days post Dose 2 time point, see below), and for 
Groups 5-6 at the time of the interim analysis when all participants in the Groups 5-6 complete the 21-day 
post booster dose visit (or discontinue earlier).
All participants will sign the informed consent form (ICF) and will be screened for eligibility at baseline 
(Day 1), which is also the day of Dose 1 vaccination. If needed, the screening activities may be split over 
multiple visits, with a maximum time of up to 28 days between signing the ICF and Dose 1 vaccination. 
Dose 2 vaccination will be given on Day 57. Participants in the immunogenicity subset and in Groups 5-6
will be followed for immunogenicity until the 21-day post Dose 2 visit (Day 78). Participants in Groups 5-
6 will in addition be followed up from pre booster dose (Day 177) until 12 months after receiving the 
booster dose (Day 537). Samples for immunogenicity assessments will be taken pre Dose 1 (Day 1), pre 
Dose 2 (Day 57), 21 days post Dose 2 (Day 78), and in Groups 5-6 also pre booster dose (Day 177), and 7 
days (Day 184), 21 days (Day 198), 6 months (Day 357), and 12 months (Day 537) after the booster dose. 
All participants will complete diary cards until 7 days post each vaccination (solicited adverse events), 
which will be reviewed by study site personnel at the Day 57 visit (before Dose 2 vaccination), at the Day 
78 visit, and at the Day 184 visits (Groups 5-6 only). Unsolicited adverse events will be recorded until 
28 days post each vaccination; participants will be asked about these at the Day 57 visit, at the Day 78 visit, 
at the Day 177, 184 and 198 visits (Groups 5-6 only), and by means of a telephone call at Days 29, 85, and 
at Day 205 (Groups 5-6 only). Serious adverse events will be recorded until the end of the study with a 
telephone call foreseen for Groups 1-4 only at 6 months post Dose 2 (Day 237). 
The investigators, together with the sponsor’s medical monitor, will be responsible for the safety monitoring 
of the study. If at least one pre-specified pausing rule is met, administration of study vaccine will be paused.
According to the sponsor’s standard procedures, a multidisciplinary Safety Management Team (SMT) is in 
place for the development of the Ebola vaccines regimen. This SMT will monitor the safety of the 
participants in this study as part of its regular surveillance of all clinical studies using the Ebola vaccines 
Ad26.ZEBOV, MVA-BN-Filo.
PARTICIPANT POPULATION
The participant population will consist of medically stable men and women 18 to 50 years of age 
(inclusive), without known prior exposure to EBOV (including travel to an area with Ebola outbreak less 
than 1 month prior to screening, if applicable) or diagnosis of Ebola virus disease (EVD). Participants who 
have received a candidate Ebola vaccine or a candidate Ad26- or MVA-based vaccine in the past or with 
known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products, 
including known allergy to chicken or egg protein and gentamicin will be excluded.

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DOSAGE AND ADMINISTRATION
All participants will receive the study vaccine (Ad26.ZEBOV and MVA-BN-Filo, or placebo) administered 
through IM injection (0.5 mL) in the deltoid muscle: 

Ad26.ZEBOV as Dose 1 (5x1010 vp, Lot A) on Day 1, followed by MVA-BN-Filo as Dose 2
(1x108 Inf U, Lot 1) on Day 57; OR

Ad26.ZEBOV as Dose 1 (5x1010 vp, Lot B) on Day 1, followed by MVA-BN-Filo as Dose 2
(1x108 Inf U, Lot 2) on Day 57; OR

Ad26.ZEBOV as Dose 1 (5x1010 vp, Lot C) on Day 1, followed by MVA-BN-Filo as Dose 2
(1x108 Inf U, Lot 3) on Day 57; OR

Ad26.ZEBOV as Dose 1 (5x1010 vp, a single Lot) on Day 1, followed by MVA-BN-Filo as Dose 2
(1x108 Inf U, a single Lot) on Day 57, followed by Ad26.ZEBOV (5x1010 vp, a single Lot) as 
booster dose, 4 months post Dose 2 (Group 5 only); OR

Placebo (0.9% saline) as Dose 1 on Day 1, followed by placebo as Dose 2 on Day 57, followed by 
placebo as booster dose on Day 177 (booster dose for Group 6 only).
IMMUNOGENICITY EVALUATIONS
Blood samples for humoral immunogenicity assessments will be collected from participants in the 
immunogenicity subset and Groups 5-6 at the time points indicated in the TIME AND EVENTS 
SCHEDULE.
SAFETY EVALUATIONS
All safety evaluations will be performed as specified in the TIME AND EVENTS SCHEDULE.
Safety will be assessed by collection of solicited local and systemic adverse events (reactogenicity), 
unsolicited adverse events, and serious adverse events. After each vaccination, participants will remain 
under observation at the study site for at least 30 minutes for presence of any acute reactions and solicited 
local and systemic events, or longer if deemed necessary by the investigator. Solicited and unsolicited
adverse events emerging during the observation period will be recorded in the electronic case report form 
(eCRF). 
Upon discharge from the study site, participants will receive a thermometer (to measure body temperature), 
a ruler (to measure local injection site reactions), and a participant diary to record body temperature and 
symptoms of solicited local (at injection site) and systemic adverse events and will be trained on how to 
collect this information. The participants will record symptoms of solicited local and systemic adverse 
events in the diary in the evening after each vaccination and then daily for the next 7 days. The diary cards 
will be reviewed by study site personnel at the Day 57 visit (before Dose 2 vaccination), at the Day 78 visit, 
and at the Day 184 visit (7 days post booster dose visit, for Groups 5-6 only).
All adverse events and special reporting situations, whether serious or nonserious, that are related to 
study-related procedures or to non-investigational (concomitant) sponsor products, and pregnancy (if 
applicable), will be reported from the time a signed and dated ICF is obtained onwards.
Other serious adverse events and special reporting situations will be reported from first dose of study 
vaccine until the end of the study.
Other nonserious adverse events and special reporting situations will be reported from first dose of study 
vaccine until 28 days after first dose of study vaccine, and from the second dose of study vaccine until 
28 days thereafter. Participants will be asked about the occurrence of unsolicited adverse events at the 

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Day 57 visit (before Dose 2 vaccination), at the Day 78 visit, and by means of a telephone call at Days 29 
and 85.
Unsolicited adverse events with the onset date outside the time frame defined above (>28 days after 
previous study vaccination), which are ongoing on the day of the subsequent vaccination, should be 
recorded on the eCRF Adverse Event page.
Clinically relevant medical events occurring between signing of ICF and first vaccination will be collected 
on the eCRF Medical History page as pre-existing conditions.
The sponsor will evaluate any safety information that is spontaneously reported by an investigator beyond 
the time frame specified in the protocol.
Other safety assessments include vital signs (blood pressure, pulse/heart rate, and body temperature), 
physical examination and pregnancy testing.
The investigators, together with the sponsor’s medical monitor, will be responsible for the safety monitoring 
of the study. If at least one pre-specified pausing rule is met, administration of study vaccine will be paused.
STATISTICAL METHODS
For the main part of the study (Groups 1-4), the primary safety and immunogenicity analyses will be 
conducted when all participants in Groups 1-4 have completed the 28-day post Dose 2 time point or 
discontinued earlier, and the database has been locked. Only sponsor personnel not involved in the review 
and determination of causality of serious adverse events reported during the study will be unblinded to 
Groups 1-4 at this time point. Investigators, study site personnel (except for those with primary 
responsibility for study vaccine preparation and dispensing), and participants will remain blinded to the 
study vaccine allocation until the last participant in Groups 1-4 completes the 6-month post Dose 2 time
point (ie, Day 237, last study related visit) or discontinues earlier (and the database is locked). An interim 
analysis will be performed when all participants in Groups 1-4 have completed the 6-month post Dose 2 
visit, ie, the last study-related visit (or discontinue earlier), and the database has been locked.
For the Booster Cohort (Groups 5-6), an interim analysis will be performed when all participants in Groups 
5-6 have completed the 28-day post booster dose time point (or discontinued earlier). This analysis, based 
on the corresponding locked database, will include all available data (including safety and 21-day post 
booster dose immunogenicity data) up to the cut off. Only sponsor personnel not involved in the review 
and determination of causality of serious adverse events reported during the study will be unblinded to 
Groups 5-6 at this time point. Investigators, study site personnel (except for those with primary 
responsibility for study vaccine preparation and dispensing), and participants will remain blinded to the 
study vaccine allocation until the database is locked for the final analysis.
The final analysis will be conducted when all participants in the study have completed the last study-related 
visit or have discontinued earlier.
A planned analysis may be combined with the subsequent analysis, if deemed necessary (eg, when the dates 
of 2 planned database locks are very close).
Descriptive statistics (including geometric means with their corresponding 95% CIs, median, interquartile 
range, minimum, maximum, as applicable) will be calculated for continuous immunologic parameters at 
each time point. Graphical representations of immunologic parameters will be prepared, as applicable. 
Frequency tabulations will be calculated for discrete (qualitative) immunologic parameters at each time 
point.
To assess the primary objective, each pairwise comparison (ie, Groups 1 vs 2, 1 vs 3, 2 vs 3) of the 
anti-EBOV GP binding antibody responses 21 days post Dose 2 vaccination with MVA-BN-Filo will be 
based on ratios of the GMCs with corresponding 95% CI. Equivalence of any 2 groups will be shown if the 

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95% CI of the estimated GMC ratio lies entirely within 0.5 and 2.0. Lot-to-lot consistency is accomplished 
if equivalence is shown for all 3 pairwise comparisons. 
For the secondary objective, each pairwise comparison of the anti-EBOV GP binding antibody responses
56 days post Dose 1 vaccination with Ad26.ZEBOV will be based on ratios of the GMCs with 
corresponding 95% CI. Equivalence of any 2 groups will be shown if the 95% CI of the estimated GMC 
ratio lies entirely within 0.5 and 2.0. Lot-to-lot consistency (for Ad26.ZEBOV) is accomplished if 
equivalence is shown for all 3 pairwise comparisons. 
As a sensitivity analyses, both the primary and secondary hypotheses of equivalence will also be tested 
based on data of participants who received the second vaccination within the original window (±3 days)
around the Day 57 visit.
Safety Analyses
No formal statistical testing of safety data is planned. All the participants who received at least 1 dose of 
the study vaccine will be included in the safety analysis. The reporting of the categorical safety data will 
include the incidence, severity, relatedness, and type of adverse events. Continuous safety parameters will 
be descriptively analyzed (showing the mean, standard deviation, median and quartiles [Q1 and Q3]).
Baseline for all vital signs and physical examinations will be defined as the last evaluation done before 
Dose 1 vaccination.

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e
Prestudy-specific therapies such as analgesic/antipyretic medications, nonsteroidal anti-inflammatory drugs, vaccines, and immunomodulators/suppressors (eg, cancer 
chemotherapeutic agents, systemic corticosteroids) administered up to 30 days prior to Dose 1 vaccination and previous vaccinia/smallpox vaccination at any time 
prior to study entry must be recorded in the electronic case report form (eCRF).
f
The investigator must check for acute illness or body temperature ≥38.0°C at the time of vaccination. In such cases, the participant may be vaccinated up to, and no 
later than 10 days after the scheduled vaccination, or be withdrawn at the discretion of the investigator and after consultation with the sponsor.
g
Prior to study vaccine administration.
h
For women of childbearing potential. 
i
A full physical examination (excluding genito-urinary system), including height and body weight, will be carried out at screening (Day 1). At other visits, an 
abbreviated, symptom-directed examination will be performed as indicated by the investigator. 
j
Includes blood pressure and pulse/heart rate (at least 5 minutes of rest in supine position), and oral temperature. 
k
Participants will receive a diary to document symptoms of solicited local and systemic adverse events (reactogenicity). At Day 1, in addition to the diary, a ruler and 
thermometer will be distributed to each participant. 
l
The participants will complete diary cards until 7 days post each vaccination (solicited adverse events), which will be reviewed by study site personnel at the Day 57 
visit (before Dose 2 vaccination) and at the Day 78 visit.
m
After each vaccination, participants will remain under observation at the study site for at least 30 minutes for presence of any acute reactions or solicited events. 
Solicited and unsolicited adverse events emerging during the observation period will be recorded in the eCRF.
n
Solicited adverse events will be documented in the evening after each vaccination and then daily for the next 7 days.
o
All adverse events and special reporting situations, whether serious or nonserious, that are related to study-related procedures or to non-investigational (concomitant) 
sponsor products, and pregnancy (if applicable), will be reported from the time a signed and dated ICF is obtained onwards. Other serious adverse events and special 
reporting situations will be reported from first dose of study vaccine until the end of the study. Other nonserious adverse events and special reporting situations will 
be reported from first dose of study vaccine until 28 days after first dose of study vaccine, and from the second dose of study vaccine until 28 days thereafter. Unsolicited 
adverse events with the onset date outside the time frame defined above (>28 days after previous study vaccination), which are ongoing on the day of the subsequent 
vaccination, should be recorded on the eCRF Adverse Event page.
p
Participants will be asked about the occurrence of unsolicited adverse events at the Day 57 visit (before Dose 2 vaccination), at the Day 78 visit, and by means of a 
telephone call at Days 29 and 85. 
q
Concomitant therapies such as analgesic/antipyretic medications, nonsteroidal anti-inflammatory drugs, vaccines, and immunomodulators/suppressors (eg, cancer 
chemotherapeutic agents, systemic corticosteroids) must be recorded from Dose 1 vaccination up to 28 days post Dose 1 vaccination and from Dose 2 vaccination up 
to 28 days post Dose 2 vaccination. All other concomitant therapies should also be recorded beyond these time frames until the end of the study (ie, 6 months post
Dose 2) if administered in conjunction with serious adverse events and pregnancies (if applicable).
r
This is not required for participants in Groups 5-6 (Booster Cohort).
s
Humoral immunogenicity assessments on Days 1, 57, and 78; determination of neutralizing antibodies against the Ad26 vector on Day 1 for Groups 5-6 (Booster 
Cohort) only.
t
Informed consent for Groups 5-6 (Booster Cohort) includes additional procedures. See below.
u
Lower limit: Day 57-3 days, upper limit: Day 57+28 days

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f
An abbreviated, symptom-directed examination will be performed as indicated by the investigator. 
g
Includes blood pressure and pulse/heart rate (at least 5 minutes of rest in supine position), and oral temperature.
h
Participants will receive a diary to document symptoms of solicited local and systemic adverse events (reactogenicity).
i
The participants will complete diary cards until 7 days post each vaccination (solicited adverse events), which will be reviewed by study site personnel at the Day 184
visit.
j
After each vaccination, participants will remain under observation at the study site for at least 30 minutes for presence of any acute reactions or solicited events. 
Solicited and unsolicited adverse events emerging during the observation period will be recorded in the eCRF.
k
Solicited adverse events will be documented in the evening after each vaccination and then daily for the next 7 days.
l
All adverse events and special reporting situations, whether serious or nonserious, that are related to study-related procedures or to non-investigational (concomitant) 
sponsor products, and pregnancy (if applicable), will be reported from the time a signed and dated ICF is obtained onwards. Other serious adverse events and special 
reporting situations will be reported from first dose of study vaccine until the end of the study. Other nonserious adverse events and special reporting situations will 
be reported from first dose of study vaccine until 28 days after booster dose of study vaccine.
m
Participants will be asked about the occurrence of unsolicited adverse events at the Day 177 visit (before booster dose vaccination), Day 184 and Day 198 visits and 
by means of a telephone call at Day 205. 
n
Concomitant therapies such as analgesic/antipyretic medications, nonsteroidal anti-inflammatory drugs, vaccines, and immunomodulators/suppressors (eg, cancer 
chemotherapeutic agents, systemic corticosteroids) must be recorded from booster dose vaccination up to 28 days post booster dose vaccination. All other concomitant 
therapies should also be recorded beyond these time frames until the end of the study if administered in conjunction with serious adverse events and pregnancies (if 
applicable).

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ABBREVIATIONS
Ad26
Adenovirus serotype 26
Ad26.ZEBOV
Adenovirus serotype 26 encoding the Ebola virus Mayinga glycoprotein
β-hCG
β-human chorionic gonadotropin
BN
Bavarian Nordic
CI
confidence interval
COVID-19
coronavirus disease 2019
EBOV
Ebola virus
eCRF
electronic case report form
eDC
electronic data capture
ELISA
enzyme-linked immunosorbent assay
EU/ml
ELISA unit/ml
EVD
Ebola virus disease
GCP
Good Clinical Practice
GMC
geometric mean concentration
GMP
Good Manufacturing Practice
GP
glycoprotein
HIV
human immunodeficiency virus
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use
IDT
IDT Biologika GmbH in Dessau-Rosslau, Germany
IEC
Independent Ethics Committee
IM
intramuscular(ly)
Inf U
infectious unit(s)
IRB
Institutional Review Board
IUD
intrauterine device
IUS
intrauterine hormone-releasing system
IWRS
interactive web response system
kb
kilobase
MARV
Marburg virus
MedDRA
Medical Dictionary for Regulatory Activities
MVA
Modified Vaccinia Ankara
MVA-BN-Filo
Modified Vaccinia Ankara Bavarian Nordic vector expressing multiple filovirus proteins
NHP
nonhuman primate(s)
NP
nucleoprotein
PCR
polymerase chain reaction
PQC
Product Quality Complaint
PREVAC
Partnership for Research on Ebola Vaccination
SAP
Statistical Analysis Plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SMT
Safety Management Team
SUDV
Sudan virus
SUSAR
suspected unexpected serious adverse reaction
TAFV
Tai Forest virus
VISP
vaccine-induced seropositivity
vp
viral particle(s)
vs
versus
WHO
World Health Organization

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DEFINITIONS OF TERMS
Study vaccine
Ad26.ZEBOV, MVA-BN-Filo, or placebo
Independent study 
vaccine monitor
An unblinded study vaccine monitor assigned to the study who is responsible for the 
unblinded interface between the sponsor and the study site pharmacy.
Solicited adverse events 
(reactogenicity)
Local (at injection site) and systemic adverse events that are common and known to occur 
after vaccination and that are usually collected in a standard, systematic format in vaccine 
clinical studies. For the list of solicited adverse events in this study, see Section 9.3. For 
the purpose of vaccine clinical studies, all other adverse events are considered unsolicited; 
however, this definition should be distinguished from definitions based on 
pharmacovigilance guidelines.
Immunogenicity subset
A subset of 456 participants in Groups 1-4 (144 in each of Groups 1 to 3 and 24 in Group 
4) that will be assessed for immunogenicity.
Study Naming Convention
Clinical studies with the Ad26.ZEBOV and MVA-BN-Filo vaccines are referred to as study VAC52150EBLXXXX 
(eg, study VAC52150EBL1001), but also the abbreviation EBLXXXX (eg, study EBL1001) is used in this document.

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1.
INTRODUCTION
Janssen Vaccines & Prevention 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 (VAC52150) comprised of the following 2 candidate Ebola vaccines:
Ad26.ZEBOV is a monovalent vaccine expressing the full-length glycoprotein (GP) of the Ebola
virus (EBOV, formerly known as Zaire ebolavirus) Mayinga variant. The vaccine 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 EBOV Mayinga GP, the Sudan virus (SUDV) Gulu GP, the 
Marburg virus (MARV) Musoke GP, and the Tai Forest virus (TAFV, formerly known as Côte 
d’Ivoire ebolavirus) nucleoprotein (NP). The EBOV GP expressed by MVA-BN-Filo has 
100% homology with the one expressed by Ad26.ZEBOV.
For the most comprehensive nonclinical and clinical information regarding Ad26.ZEBOV and 
MVA-BN-Filo, refer to the latest versions of the Investigator’s Brochures (IB) and Addenda.3,4 A 
brief summary of the clinical information available at the time of the protocol writing is provided 
below.
The term “study vaccine” throughout the protocol, refers to study vaccine (Ad26.ZEBOV, 
MVA-BN-Filo), or placebo.
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 (EVD), which can 
induce severe hemorrhagic fever in humans and nonhuman primates (NHP). Case fatality rates in 
Ebola disease range from 25%to90% (average: 50%), according to the World Health Organization 
(WHO).6 These viruses are highly prioritized by the United States Government, who has defined 
them as ‘Category A’ agents, due to the high mortality rate of infected individuals. Currently, no 
cure exists and no vaccine has been licensed in Europe or the United States for this disease. 
Filoviruses are named for their long, filamentous shape. Within this filamentous virus, a single 
19-kilobase (kb) negative-sense RNA genome encodes 7 proteins: the GP, the polymerase, the NP, 
the secondary matrix protein, the transcriptional activator, the polymerase cofactor, and the matrix 
protein. The virion surface is covered by homotrimers of the viral GP, which is believed to be the 
sole host attachment factor for filoviruses. Following cell entry, the viruses replicate their genomes 
and viral proteins in the cytoplasm using an RNA-dependent RNA polymerase, which is carried 
into the cell together with the virus.2
In this Phase 3 study, the sponsor’s adenovirus serotype 26 (Ad26) vector expressing the EBOV 
Mayinga GP (Ad26.ZEBOV) and the MVA-BN vector with EBOV, SUDV, and MARV GP and 
TAFV NP inserts (MVA-BN-Filo) will be evaluated as a heterologous 2-dose vaccine regimen, in 

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which one study vaccine (Ad26.ZEBOV) is used to induce an EBOV-specific immune response 
and the other study vaccine (MVA-BN-Filo), administered 56 days later, is used to enhance the 
immune response. The EBOV GP that circulated in West Africa during the 2014-2016 epidemic 
had 97% homology with the EBOV GP used in this vaccine regimen.1
For an overview of the nonclinical studies with Ad26.ZEBOV and MVA-BN-Filo, refer to the 
respective IBs.3,4
Clinical Studies
The safety, reactogenicity, and immunogenicity of the Ad26.ZEBOV and MVA-BN-Filo vaccines 
are being evaluated in a number of completed and ongoing clinical studies in adults and children 
≥1 year of age. The sponsor’s current clinical development plan contains 4 completed Phase 1 
studies (EBL1001, EBL1002, EBL1003, and EBL1004), the ongoing Phase 1 study EBL1007, 
1 completed Phase 2 study (EBL2001), 3 ongoing Phase 2 studies (EBL2002, EBL2003, and 
EBL2004/Partnership for Research on Ebola Vaccination [PREVAC]), 2 completed Phase 3 
studies (EBL3002 and EBL3003) and 3 ongoing Phase 3 studies (EBL3001, EBL3005, and 
EBL4001). A planned Phase 2 study (EBL2005) will evaluate the safety and immunogenicity of 
the vaccine regimen in infants aged 4-11 months. In addition, 2 Phase 2 studies in adult health care 
and frontline workers in Africa (EBL2007 and EBL2009) and 2 Phase 3 studies (EBL3008
[vaccine deployment in the Democratic Republic of the Congo] and EBL3009 [vaccination of 
sponsor employees in case of deployment in high-risk situations]) are planned. An additional 
Phase 1 study with the multivalent vaccine VAC69120FLV1001 has been completed, where a 
group receiving Ad26.ZEBOV, MVA-BN-Filo in a 56-day interval was included as a control arm.
The data from this control arm support the safety and immunogenicity of the Ad26.ZEBOV, 
MVA-BN-Filo vaccine regimen in a 56-day interval.
As of 19 April 2019, an estimated 6,800 participants (estimation based on randomization ratios)
have received at least the Dose 1 vaccination (Ad26.ZEBOV, MVA-BN-Filo, or placebo/active 
comparator), including approximately 1,800 children (1-17 years of age) and 400 human 
immunodeficiency virus (HIV)+ adults who have been vaccinated.
Refer to the latest versions of the Ad26.ZEBOV and MVA-BN-Filo IBs and Addenda for more 
details.3,4 A summary is provided below.
Phase 1 Studies
Final analysis data are available for the 4 randomized, placebo-controlled, observer-blind, Phase 1 
studies that were conducted in healthy adult Western (United Kingdom and United States) and 
African (Kenya, Tanzania, and Uganda) male and female participants, aged ≥18 to ≤50 years, 
outside of EBOV outbreak areas. In these studies, Ad26.ZEBOV and MVA-BN-Filo were
administered intramuscularly (IM) as homologous or heterologous 2-dose vaccine regimens, in 
7-, 14-, 28-, or 56-day intervals.
Both vaccines are well tolerated, with no safety concerns identified. Reactogenicity was slightly 
more commonly reported among participants following Ad26.ZEBOV than following 
MVA-BN-Filo vaccination. The most frequently reported solicited adverse events reported in the 

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4 individual Phase 1 studies were injection site pain, injection site warmth, fatigue, headache, and 
myalgia. The most frequently reported unsolicited adverse events were hypokalemia, neutropenia, 
and neutrophil count decreased. 
The Ad26.ZEBOV, MVA-BN-Filo vaccine regimens are highly immunogenic and induce 
considerable humoral as well as cellular immune responses, regardless of vaccine sequence and 
dose level.
Phase 2/3 Studies 
In the ongoing, randomized, controlled Phase 2/3 studies, enrollment of both adults and children 
is complete. The safety data from 5 Phase 2/3 studies (EBL2001, EBL2002, EBL3001, EBL3002, 
and EBL3003) were unblinded to the group level in response to the May 2018 outbreak in the 
Democratic Republic of the Congo. The serious adverse event databases have been reconciled and 
include, in addition to the studies listed below, serious adverse event data from 
EBL2004/PREVAC.
In general, the vaccine regimen of Ad26.ZEBOV followed by MVA-BN-Filo 56 days later was 
well tolerated and no safety signals were identified. The majority of solicited adverse events were 
of mild or moderate intensity after vaccination with Ad26.ZEBOV or MVA-BN-Filo. The 
frequency of grade 3 pyrexia (≥39.0 C) was less than 1% following vaccination and the incidence 
of any febrile response was less than 7.5% in any group. As expected, the frequency of local and 
systemic reactogenicity was more common in healthy adult participants who received active 
vaccine compared to placebo and was similar to the incidence reported in the Phase 1 studies. 
Reactogenicity was also slightly more commonly reported among participants following 
Ad26.ZEBOV than following MVA-BN-Filo vaccination which was also noted in the Phase 1 
studies.
A review of the unblinded safety summary reveals that serious adverse events were reported in 
46 healthy adults (2.2%) vaccinated with the active vaccine regimen and in 9 participants (2.2%) 
vaccinated with placebo. There was 1 serious adverse event reported in HIV-infected adults which 
occurred in the active vaccine group. From the still blinded studies, a total of 35 serious adverse 
events have been reported in adults, adolescents, and children in study EBL2004/PREVAC. 
One suspected unexpected serious adverse reaction (SUSAR) of small fiber neuropathy was 
reported following administration of Ad26.ZEBOV and 1 SUSAR of generalized pruritus was 
reported following administration of MVA-BN-Filo. There are no adverse drug reactions or events 
of special concern listed in the IBs.
In the ongoing clinical studies with Ad26.ZEBOV, there have been a few reports of mild to 
moderate paresthesia especially in the hands and feet or a sensation of mild to moderate muscle 
weakness in participants vaccinated with Ad26.ZEBOV or placebo. These symptoms have been 
observed to last no more than 24 to 48 hours in the majority of cases but can last for several weeks 
before resolving spontaneously. These types of symptoms have been reported following 
administration of other licensed vaccines and following acute viral infections of various types. 
One serious adverse event of probable peripheral sensory neuropathy (nerve damage that may 

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cause tingling, numbness, pain, or loss of pain sensation) of moderate severity has occurred and 
has been ongoing for several months, interfering with some of the participant’s daily activities (for 
details, refer to the Ad26.ZEBOV IB, Edition 6).3
The Phase 2/3 studies confirm the immunogenicity of the Ad26.ZEBOV, MVA-BN-Filo regimen.
1.2.
Benefit/Risk Section
1.2.1.
Known Benefits
The clinical benefit of a 2-dose combination of Ad26.ZEBOV and MVA-BN-Filo is to be 
established.
1.2.2.
Potential Benefits
Participants may benefit from clinical testing and physical examination; others may benefit from 
the knowledge that they may aid in the development of an Ebola vaccine. There is no direct 
individual benefit from vaccination for the participants at the current development stage.
1.2.3.
Known Risks 
The safety, reactogenicity, and immunogenicity of the Ad26.ZEBOV and MVA-BN-Filo vaccines 
are being evaluated in a number of completed and ongoing clinical studies in adults and children 
≥1 year of age. Both vaccines are well tolerated, with no safety concerns identified. The vaccines
mainly elicited some symptoms of solicited local and systemic reactions, as expected with 
injectable vaccines, and no serious safety concerns in participants. MVA-BN-based vaccines have 
been administered to more than 13,300 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 are specified in the protocol 
and will be monitored during the study.
Risks Related to Vaccination
In general, IM injection may cause local itching, warmth, pain, tenderness, erythema/redness, 
induration/swelling, arm discomfort, or bruising of the skin at vaccine injection sites.
Participants may exhibit general signs and symptoms associated with administration of a vaccine, 
including fever, chills, rash, myalgia, nausea/vomiting, headache, dizziness, arthralgia, general 
itching, and fatigue. These side effects will be monitored, but are generally short-term and do not 
require treatment.
Syncope can occur in association with administration of injectable vaccines and syncope can be 
accompanied by falls. Procedures should be in place to avoid falling injury. If syncope develops, 
participants should be observed until the symptoms resolve. Fear of injection might lead to fainting 
and fast breathing.

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Participants may have an allergic reaction to the vaccination. An allergic reaction may cause a 
rash, urticaria, or anaphylaxis. Severe reactions are rare. Medications must be available in the 
clinic to treat serious allergic reactions. Participants with a known allergy, or history of 
anaphylaxis or other serious adverse reactions to vaccines or vaccine products (including any of 
the constituents of the study vaccine) will be excluded from the study.
Risks From Blood Draws
As with all clinical studies requiring blood sampling, there are risks associated with venipuncture 
and multiple blood sample collection. Blood drawing may cause pain, tenderness, bruising, 
bleeding, dizziness, vasovagal response, syncope, and, rarely, infection at the site where the blood 
is taken. The total blood volume to be collected is considered to be an acceptable amount of blood 
over this time period from the population in this study (see Section 16.1). 
Vaccine-Induced Seropositivity
In general, uninfected participants who are taking part in Ebola vaccine studies may develop 
Ebola-specific antibodies as a result of an immune response to the candidate Ebola vaccine, 
referred to as vaccine-induced seropositivity (VISP). These antibodies may be detected in Ebola 
serologic tests, causing the test to appear positive even in the absence of actual Ebola infection. 
VISP may become evident during the study, or after the study has been completed. The potential 
of a participant becoming PCR-positive after vaccination was
assessed in study 
VAC52150EBL1002. None of the participants tested positive for EBOV after vaccination.
Consent will be obtained to contact the doctors that the participant sees regularly, to let them know 
that the participant is taking part in this study. It is important for all of the participant’s doctors to 
know that the participant may be administered experimental vaccines. Participants will be provided 
with a "wallet (study) card" and instructed to carry this card with them for the duration of the study 
(see Section 12.3.1).
Pregnancy and Birth Control
The effect of the vaccines on a fetus or nursing baby is unknown. Female participants of 
childbearing potential will be required to agree to use birth control for sexual intercourse beginning 
28 days prior to vaccination and continuing until at least 3 months post Dose 1 vaccination,
28 days post Dose 2 vaccination, or 3 months post booster vaccination (Groups 5-6 only), 
whichever comes later. Women who are pregnant or breast-feeding may not receive further study 
vaccines but may continue other study procedures at the discretion of the investigator.
Male participants should inform the investigator and the sponsor in case their partner would 
become pregnant during the study.
Unknown Risks 
There may be other risks that are not known. If any significant new risks are identified, the 
investigator and participants will be informed.

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1.2.5.
Overall Benefit/Risk Assessment
Based on the available data and proposed safety measures, the overall benefit/risk assessment for 
this clinical study is considered acceptable for the following reasons:

To date, safety data from the studies in the clinical development program revealed no 
significant safety issues (see Section 1.1). Further experience from Ad26.ZEBOV or
MVA-BN-Filo will be gained from currently ongoing clinical studies.

Only participants who meet all inclusion criteria and none of the exclusion criteria (specified 
in Section 4) will be allowed to participate in this study. The selection criteria include adequate 
provisions to minimize the risk and protect the well-being of participants in the study.

Several safety measures are included in this protocol to minimize the potential risk to 
participants, including the following:

Participants will remain under observation at the study site for at least 30 minutes after 
each vaccination for presence of any acute reactions and solicited events, or longer if 
deemed necessary by the investigator (eg, in case of grade 3 adverse events). Refer to 
Section 6 for more information on emergency care. 

Safety evaluations (physical examinations and vital sign measurements) will be 
performed at scheduled visits during the study, as indicated in the TIME AND EVENTS 
SCHEDULE.

The investigator or clinical designee will document unsolicited adverse events as 
indicated in Section 12.3.1.

Any clinically significant abnormalities (including those persisting at the end of the 
study/early withdrawal) will be followed by the investigator until resolution or until a 
clinically stable endpoint is reached.

There are pre-specified pausing rules for all participants, that would result in pausing of 
further vaccination if predefined conditions occur, preventing exposure of new 
participants to study vaccine until the sponsor reviews all safety data (see Section 9.3.2).

Participants will discontinue study vaccine for the reasons included in Section 10.2.

If acute illness (excluding minor illnesses such as diarrhea or mild upper respiratory tract 
infection) or fever (body temperature ≥38.0°C) occur at the scheduled time for 
vaccination, the participant may be vaccinated up to 10 days beyond the window allowed 
for the scheduled vaccination, or be withdrawn from that vaccination at the discretion of 
the investigator and after consultation with the sponsor (see Section 6.1).

Contraindications to Dose 2 and booster dose vaccination are included in Section 6.2.
1.3.
Overall Rationale for the Study
This Phase 3 study aims to show lot-to-lot consistency of the vaccine regimen by demonstrating 
that paired 2-dose vaccine regimens from 3 consecutively manufactured lots of Ad26.ZEBOV 
drug product (Dose 1) and 3 consecutively manufactured lots of MVA-BN-Filo drug product 
(Dose 2) elicit equivalent humoral immune responses. The 3 consecutive lots are Lots A, B, and C 
for Ad26.ZEBOV and Lots 1, 2, and 3 for MVA-BN-Filo and these lots will be compared in 

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3 different groups (ie, A:1 [Group 1], B:2 [Group 2], and C:3 [Group 3]) (see Section 3.1, Table 1). 
The results of this study will also aid in increasing the size of the overall safety and 
immunogenicity data packages to support approval of the Ad26.ZEBOV, MVA-BN-Filo 2-dose 
vaccine regimen by a regulatory authority.
Administration of a booster dose of Ad26.ZEBOV given at 1- and 2 years post Dose 1 in studies 
VAC52150EBL1002, VAC52150EBL2002, and VAC52150EBL3001 induced a rapid and robust 
anamnestic response to the booster vaccine. Administration of a booster dose in anticipation of 
imminent exposure to Ebola (ie, prior to deployment to an Ebola outbreak area) may be desired as
a precautionary measure to optimize protection. However, there is currently no clinical data 
available on the immunogenicity and safety of such an Ad26.ZEBOV booster dose when 
administered less than 1 year after the primary vaccine regimen. Booster doses as early as 
2-3 months after Dose 2 were assessed in a multivalent filovirus and an HIV vaccine program and 
were able to induce a marked increase in antibody concentrations, although to a lower magnitude 
than a later booster. Furthermore, based on the kinetics of decrease in antibody concentrations after 
the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen, supported by a mechanistic model of antibody 
persistence and general vaccine knowledge, an Ad26.ZEBOV booster dose administered from 4 
months after completion of the primary vaccine regimen is likely to induce a strong anamnestic 
response based on mature immune memory and to maximize the likelihood of protection in case 
of imminent risk of exposure to Ebola. Therefore, a separate Booster Cohort of participants will 
receive the primary vaccine regimen followed by a booster dose of Ad26.ZEBOV 4 months after 
Dose 2. The participants in this Booster Cohort (Groups 5-6) will be assessed for safety and 
immunogenicity. 
2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESES
2.1.
Objectives and Endpoints
Objectives
Endpoints
Primary

To demonstrate that the paired 2-dose vaccine
regimens from 3 consecutively manufactured
lots of Ad26.ZEBOV as Dose 1
and 
3 consecutively manufactured lots of MVA-
BN-Filo as Dose 2, administered at a 56-day 
interval,
induce an equivalent humoral 
immune response.

Binding antibody levels against the EBOV GP 
using enzyme-linked immunosorbent assay 
(ELISA, ELISA units/mL [EU/mL]) at 
21 days post Dose 2 vaccination.
Secondary

To 
demonstrate 
that 
3
consecutively 
manufactured lots of Ad26.ZEBOV as Dose 1
induce an equivalent humoral immune 
response.

Binding antibody levels against the EBOV GP 
using ELISA (EU/mL) at 56 days post Dose 1
vaccination.

To assess the safety and reactogenicity of a 
heterologous 2-dose vaccine
regimen of 
Ad26.ZEBOV 
and 
MVA-BN-Filo 
administered 
IM 
on 
Days 1 
and 
57, 
respectively, 
using 
3 different 
lots 
of 

Solicited local and systemic adverse events 
until 7 days post each vaccination.

Unsolicited adverse events until 28 days post
each vaccination.

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Objectives
Endpoints
Ad26.ZEBOV 
and 
3 different 
lots 
of 
MVA-BN-Filo.

Serious adverse events until the end of the 
study.
Exploratory (Booster Cohort only)

To assess the humoral immune response to a 
booster dose of Ad26.ZEBOV given 4 
months after Dose 2.

Binding antibody levels against the EBOV GP 
using ELISA (EU/mL) at pre booster 
(Day 177) and several post booster timepoints 
(7-days, 21-days, 6-months and 12-months 
post booster dose).

To assess the safety and reactogenicity of a 
booster dose of Ad26.ZEBOV.

Solicited local and systemic adverse events 
until 7 days post booster vaccination.

Unsolicited adverse events until 28 days post 
booster vaccination.

Serious adverse events until the end of the 
study.

To assess the presence of neutralizing 
antibodies against the Ad26 vector.

Viral neutralizing antibody levels against the
Ad26 
vector 
at 
baseline,
pre 
booster 
vaccination (Day 177), and at 21 days post 
booster vaccination.
Refer to Section 9 for evaluations related to endpoints.
2.2.
Hypotheses
2.2.1.
Primary Hypotheses
Null Hypothesis: 
Three consecutive lots of Ad26.ZEBOV (Lots A, B, and C) as Dose 1 paired sequentially in 
3 groups with 3 consecutive lots of MVA-BN-Filo (Lots 1, 2, and 3) as Dose 2 do not induce 
equivalent geometric mean concentrations (GMCs) of the EBOV GP-specific antibody response 
21 days post Dose 2, for at least one pairwise comparison.
Alternative Hypothesis: 
Three consecutive lots of Ad26.ZEBOV (Lots A, B, and C) as Dose 1 paired sequentially in 
3 groups with 3 consecutive lots of MVA-BN-Filo (Lots 1, 2, and 3) as Dose 2 induce equivalent 
GMCs of the EBOV GP-specific antibody response 21 days post Dose 2, for all 3 pairwise 
comparisons (ie, Groups 1 versus [vs] 2, 1 vs 3 and 2 vs 3 [see schematic overview of the study 
and groups in Section 3.1, Table 1]).
Equivalence of any 2 groups (Ad26.ZEBOV as Dose 1 followed by MVA-BN-Filo as Dose 2) will 
be shown if the 95% confidence interval [CI] of the estimated GMC ratio lies entirely within 
0.5 and 2.0. These equivalence limits were chosen primarily based on the population variability as 
measured by the ELISA assay. Immunogenic equivalence of the 3 different lots of Ad26.ZEBOV 
(Lots A, B, and C) paired sequentially in 3 groups with 3 different lots of MVA-BN-Filo (Lots 1, 
2, and 3) is established if equivalence is shown for all 3 pairwise comparisons.

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2.2.2.
Secondary Hypotheses
The secondary hypotheses will be tested on the EBOV GP-specific antibody response 56 days post
Dose 1. Similar null and alternative hypotheses will be formulated and tested using the same 
criteria as outlined for the primary hypotheses.
3.
STUDY DESIGN AND RATIONALE
3.1.
Overview of Study Design
This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter, Phase 3 study
to evaluate lot-to-lot consistency of the manufacturing process by assessing the immunogenicity
of the final product of 3 consecutively manufactured lots of Ad26.ZEBOV at a nominal dose of 
5x1010 viral particles (vp) as Dose 1 and 3 consecutively manufactured lots of MVA-BN-Filo at a 
nominal dose of 1x108 infectious units (Inf U) as Dose 2 at a 56-day interval in adult participants
(Groups 1-4). Once randomization of this part of the study is finished, an additional Booster Cohort 
of 60 participants will be enrolled in a 5:1 active:placebo ratio. These participants will be given 
the 2-dose heterologous vaccine regimen Ad26.ZEBOV (at a nominal dose of 5x1010 vp) followed 
by MVA-BN-Filo (at a nominal dose of 1x108 Inf U) 56 days later, and a booster dose of 
Ad26.ZEBOV (at a nominal dose of 5x1010 vp) 4 months after Dose 2, or placebo (Groups 5-6).
The 3 consecutive Ad26.ZEBOV drug product lots that will be used in the study have been 
manufactured at the final manufacturing site (ie, IDT Biologika GmbH in Dessau-Rosslau, 
Germany [IDT]) and are representative of the final manufacturing process and scale (Lots A, B, 
and C). The 3 consecutive MVA-BN-Filo drug product lots that will be used have been 
manufactured at the final manufacturing site (IDT) and are representative of the final 
manufacturing process and scale (Lots 1, 2, and 3). Lots A, B, and C and Lots 1, 2, and 3 are paired 
sequentially in 3 groups (ie, A:1 [Group 1], B:2 [Group 2], and C:3 [Group 3]) of the study. 
Group 4 will receive 2 placebo vaccinations.
In the main part of the study (Groups 1-4), a planned total number of at least 741 participants will 
be enrolled. All participants in this part of the study will be assessed for safety and reactogenicity; 
456 participants (144 in each of Groups 1 to 3 and 24 in Group 4) will be assessed for 
immunogenicity (immunogenicity subset). Participants will be randomly assigned to one of 
4 groups in a 6:6:6:1 ratio, ie, to one of the 3 groups receiving Ad26.ZEBOV and MVA-BN-Filo 
(Groups 1 to 3) with a total of at least 234 participants per group, or to a placebo group (Group 4) 
with 39 participants, and the first 456 participants belonging to the immunogenicity subset.
Due to the recent (on 11 March 2020) WHO declared COVID-19 pandemic, a potential higher 
dropout rate (ie, higher than 5%) may occur. In addition, some participants in the immunogenicity 
subset may be excluded from primary immunogenicity equivalence testing because of:

Participant not receiving Dose 2; OR

Participant receiving Dose 2 outside the protocol-defined window; OR

Participant not attending the 21-day post Dose 2 visit; OR

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
Participant attending the 21-day post Dose 2 visit outside the protocol-defined window.
To mitigate these issues, additional participants may be recruited in the immunogenicity subset.
Shortly after participants received Dose 1 vaccination, ‘stay-at-home’ orders were imposed in the 
areas where the sites were located. Although the sites had implemented appropriate safety 
measures to prevent spread of SARS-CoV-2, approximately 22% of participants did not return to 
the site within the protocol defined windows (±3 days) for Dose 2 administration. Investigators 
were instructed to bring participants back to the site to complete the vaccine regimen, even if they 
were out of window. Currently, the stay-at-home orders have been lifted and participants are now 
able to return to the sites for follow-up. In order to reduce the number of additional participants 
needed for the primary and secondary immunogenicity analyses, it is possible to widen the 
acceptable window around Dose 2 administration without jeopardizing the primary and secondary 
objectives of the study. The protocol has been amended to widen the upper limit of the window 
around Day 57 (Dose 2) to Day 85 (ie, Day 57+28 days). Therefore, the number of additional 
participants necessary for inclusion in the immunogenicity subset and who would receive their 
second vaccination within the Day 57 window will be reduced.
For the Booster Cohort (Groups 5-6), a planned total of 60 participants will be enrolled. All 
participants in this cohort will be assessed for safety, reactogenicity, and immunogenicity. 
Participants will be randomly assigned to the 2 groups in a 5:1 ratio, ie, to a group of approximately 
50 participants receiving the primary vaccine regimen (Ad26.ZEBOV followed by MVA-BN-Filo 
56 days later) followed by a booster dose of Ad26.ZEBOV 4 months after Dose 2 (Group 5), or, 
to a placebo group of approximately 10 participants (Group 6).
These 2 additional Groups (5 and 6) have not yet been recruited. It is expected that these additional 
groups will likely receive their second dose in the fall of 2020, at which time it is possible that a 
second wave of COVID-19 may occur. The window for Dose 2 for these groups, therefore, is only 
being increased to 1 week to try to assure that Dose 2 is completed before a recurrence of 
COVID-19. 
Furthermore, the window for Dose 2 is limited to 1 week so as not to impact analysis of the 
anamnestic response to the booster dose. If the window for Dose 2 is further extended such that 
the time between Dose 2 and the booster dose is decreased, the primary response to the initial 
2-dose regimen may not have reached a plateau at the time the booster dose is given. In that event, 
it would be difficult to distinguish the primary response from the anamnestic response. To avoid 
this possibility, the window for Dose 2 is limited to 1 week.
The participant population will consist of medically stable men and women 18 to 50 years of age 
(inclusive), without known prior exposure to EBOV (including travel to an area with Ebola 
outbreak less than 1 month prior to screening, if applicable) or diagnosis of EVD. Participants who 
have received a candidate Ebola vaccine or a candidate Ad26- or MVA-based vaccine in the past 
or with known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or 
vaccine products, including known allergy to chicken or egg protein and gentamicin will be 
excluded.
The participants will be randomized at baseline (Day 1) to receive the 2-dose vaccine regimen with 
either Ad26.ZEBOV and MVA-BN-Filo, or placebo. Randomization of the Booster Cohort 
(Groups 5-6) will take place once randomization of the main part of the study (Groups 1-4) has 
been completed. Randomization will be done by the interactive web response system (IWRS). 

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A schematic overview of the study design and groups is provided in Table 1. For Groups 1-4, 
investigators, study site personnel (except for those with primary responsibility for study vaccine
preparation and dispensing), and participants will remain blinded to the study vaccine allocation 
until the last participant in these groups completes the 6-month post Dose 2 time point
(ie, Day 237) or discontinues earlier (and the database is locked). For Groups 5-6, investigators, 
study site personnel (except for those with primary responsibility for study vaccine preparation
and dispensing), and participants will be blinded until the end of the study. Only sponsor personnel 
not involved in the review and determination of causality of serious adverse events reported during 
the study will be unblinded for Groups 1-4 at the time of the primary safety and immunogenicity 
analyses (28 days post Dose 2 time point, see below), and for Groups 5-6 at the time of the interim 
analysis when all participants in Groups 5-6 have completed the 28-day post booster dose 
timepoint (or discontinued earlier).
Table 1:
Schematic Overview of Study Design and Groups
Groups
N
Dose 1
Dose 2
Booster Dose
Day 1
Day 57
Day 177
1
234
Ad26.ZEBOV – Lot A
MVA-BN-Filo – Lot 1 
2
234
Ad26.ZEBOV – Lot B
MVA-BN-Filo – Lot 2 
3
234
Ad26.ZEBOV – Lot C
MVA-BN-Filo – Lot 3
4
39
Placebo
Placebo
5
50
Ad26.ZEBOVa
MVA-BN-Filob
Ad26.ZEBOVa
6
10
Placebo
Placebo
Placebo
N: number of participants to receive study vaccine.
Ad26.ZEBOV dose level is 5x1010 vp and MVA-BN-Filo dose level is 1x108 Inf U, placebo is 0.9% saline.
a,b Actual lots to be determined later
All participants will receive the study vaccine (Ad26.ZEBOV and MVA-BN-Filo, or placebo) 
administered through IM injection (0.5 mL) in the deltoid muscle: 
Ad26.ZEBOV as Dose 1 (5x1010 vp, Lot A) on Day 1, followed by MVA-BN-Filo as Dose 2
(1x108 Inf U, Lot 1) on Day 57; OR
Ad26.ZEBOV as Dose 1 (5x1010 vp, Lot B) on Day 1, followed by MVA-BN-Filo as Dose 2 
(1x108 Inf U, Lot 2) on Day 57; OR
Ad26.ZEBOV as Dose 1 (5x1010 vp, Lot C) on Day 1, followed by MVA-BN-Filo as Dose 2
(1x108 Inf U, Lot 3) on Day 57; OR
Ad26.ZEBOV as Dose 1 (5x1010 vp, a single Lot) on Day 1, followed by MVA BN Filo as 
Dose 2 (1x108 Inf U, a single Lot) on Day 57, followed by Ad26.ZEBOV (5x1010 vp, a single 
Lot) as booster dose, 4 months post Dose 2 (Group 5 only); OR
Placebo (0.9% saline) as Dose 1 on Day 1, followed by placebo as Dose 2 on Day 57, followed 
by placebo as booster dose on Day 177 (booster dose for Group 6 only).
All participants will sign the informed consent form (ICF) and will be screened for eligibility at 
baseline (Day 1), which is also the day of Dose 1 vaccination. If needed, the screening activities 

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may be split over multiple visits, with a maximum time of up to 28 days between signing of the 
ICF and Dose 1 vaccination. Dose 2 vaccination will be given on Day 57. Participants in the 
immunogenicity subset and in Groups 5-6 will be followed for immunogenicity until the 21-day 
post Dose 2 visit (Day 78). Participants in Groups 5-6 will in addition be followed up from pre 
booster dose (Day 177) until 12 months after receiving the booster dose (Day 537). Samples for 
immunogenicity assessments will be taken pre Dose 1 (Day 1), pre Dose 2 (Day 57), 21 days post 
Dose 2 (Day 78), and in Groups 5-6 also pre booster dose (Day 177), and 7 days (Day 184), 21 
days (Day 198), 6 months (Day 357), and 12 months (Day 537) after the booster dose. All 
participants will complete diary cards until 7 days post each vaccination (solicited adverse events), 
which will be reviewed by study site personnel at the Day 57 visit (before Dose 2 vaccination), at 
the Day 78 visit, and at the Day 184 visit (Groups 5-6 only). Unsolicited adverse events will be 
recorded until 28 days post each vaccination; participants will be asked about these at the Day 57 
visit, at the Day 78 visit, at the Day 177, 184 and 198 visits (Groups 5-6 only), and by means of a 
telephone call at Days 29 and 85, and at Day 205 (Groups 5-6 only). Serious adverse events will 
be recorded until the end of the study with a telephone call foreseen for Groups 1-4 only at 6 
months post Dose 2 (Day 237).
For the main part of the study (Groups 1-4), the primary safety and immunogenicity analyses will 
be performed when all participants in the main part of the study (Groups 1-4) have completed the 
28-day post Dose 2 time point or discontinued earlier, and the database is locked. Only sponsor 
personnel not involved in the review and determination of causality of serious adverse events 
reported during the study will be unblinded to Groups 1-4 at this time point. An interim analysis 
will be performed when all participants in Groups 1-4 have completed the 6-month post Dose 2 
visit, ie, the last study-related visit (or discontinue earlier), and the database has been locked.
For the Booster Cohort (Groups 5-6), an interim analysis will be performed when all participants 
in Groups 5-6 have completed 28-day post booster dose time point (or discontinued earlier). This 
analysis, based on the corresponding locked database, will include all available data (including 
safety and 21-day post booster dose immunogenicity data) up to the cut off. Only sponsor 
personnel not involved in the review and determination of causality of serious adverse events 
reported during the study will be unblinded to Groups 5-6 at this time point.
The final analysis will be performed when all participants in the study have completed the last 
study-related visit or have discontinued earlier (and the database is locked). 
A planned analysis may be combined with the subsequent analysis, if deemed necessary (eg, when 
the dates of 2 planned database locks are very close).
The study is considered completed when the last participant has completed the last study 
procedure.
The investigators, together with the sponsor’s medical monitor, will be responsible for the safety 
monitoring of the study. If at least one pre-specified pausing rule is met, administration of study 
vaccine will be paused (see Section 9.3.2 for details). As per Janssen standard procedures, a 
multidisciplinary Safety Management Team (SMT) is in place for the development of the Ebola 

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vaccines regimen. This SMT will monitor the safety of the participants in this study as part of its 
regular surveillance of all clinical studies using the Ebola vaccines Ad26.ZEBOV, MVA-BN-Filo
(see Section 9.3.1 for details).
3.2.
Study Design Rationale
Control and Blinding
A placebo control will be used to establish the frequency and magnitude of changes in clinical
endpoints that may occur in the absence of active study vaccine. Randomization will be used to 
minimize bias in the assignment of participants to vaccination groups, to increase the likelihood 
that known and unknown participant attributes (eg, demographic and baseline characteristics) are 
evenly balanced across vaccination groups, and to enhance the validity of statistical comparisons 
across vaccination groups. Blinded vaccination will be used to reduce potential bias during data 
collection and evaluation of clinical endpoints.
Vaccination Groups
Groups 1, 2, and 3 will only differ in the lots of the study vaccine, while the dose of each vaccine 
and the sequence of vaccination will be identical. For Groups 1, 2, 3 and 5, Dose 1 consists of 
Ad26.ZEBOV at a nominal dose of 5x1010 vp and Dose 2 consists of MVA-BN-Filo at a nominal 
dose of 1x108 Inf U. For Group 5, the booster dose consists of Ad26.ZEBOV at a nominal dose of 
5x1010 vp from a single lot. Groups 4 and 6 will receive placebo.
4.
PARTICIPANT POPULATION
Screening for eligible participants will be performed at baseline (Day 1), which is also the day of 
Dose 1 vaccination. If needed, the screening activities may be split over multiple visits, with a 
maximum time of up to 28 days between signing of the ICF and Dose 1 vaccination.
The inclusion and exclusion criteria for enrolling participants 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 participant in the study. Waivers are not allowed. 
For a discussion of the statistical considerations of participant selection, refer to Section 11.2.
4.1.
Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1.
Signed an ICF indicating that he or she understands the purpose of, and procedures 
required for, the study as well as the potential risks and benefits of the study, and is willing 
to participate in the study.
2.
Man or woman, 18 to 50 years of age, inclusive, on the day of signing the ICF.

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3.
Medically stable in the investigator’s clinical judgment on the basis of physical 
examination, medical history, and vital signs performed at screening.
4.
Criterion modified per Amendment 2
4.1 Before randomization, a woman must be either:
a.
Not of childbearing potential;
b.
Of childbearing potential and practicing an acceptable effective method of birth 
control and agrees to remain on such a method of birth control from signing the ICF 
until at least 3 months post Dose 1 vaccination or 28 days post Dose 2 vaccination or 
3 months post booster vaccination (Groups 5-6 only), whichever comes later. Use of 
hormonal contraception should start at least 28 days before the first administration of 
study vaccine. Acceptable effective methods for this study include: 
1)
hormonal contraception;
2)
intrauterine device (IUD);
3)
intrauterine hormone-releasing system (IUS);
4)
male or female condom with or without spermicide;
5)
cap, diaphragm, or sponge with a vaginal spermicide;
6)
vasectomized partner (the vasectomized partner should be the sole partner for 
that participant);
7)
sexual abstinence*.
*Sexual abstinence is considered an effective method only if defined as refraining from 
heterosexual intercourse from signing the ICF until at least 3 months post Dose 1 vaccination 
or 28 days post Dose 2 vaccination, whichever comes later. The reliability of sexual abstinence 
needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle 
of the participant.
5.
Women of childbearing potential must have a negative urine -hCG pregnancy test at
screening and immediately prior to each study vaccine administration.
6.
Available and willing to participate for the duration of the study and follow-up visit.
7.
Willing and able to comply with the protocol requirements, including the prohibitions and 
restrictions specified in Section 4.3.
8.
Willing to provide verifiable identification.
9.
Having a means to be contacted.
Contraceptive (birth control) use by women should be consistent with local regulations regarding 
the acceptable methods of birth control for those participating in clinical studies.
Typical use failure rates may differ from those when used consistently and correctly. Use should 
be consistent with local regulations regarding the use of birth control methods for participants in 
clinical studies.

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4.2.
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from 
participating in the study:
1.
Having received any candidate Ebola vaccine.
2.
Diagnosed with EVD, or prior exposure to Ebola virus, including travel to an area with 
Ebola outbreak less than 1 month prior to screening (if applicable).
3.
Having ever received any experimental candidate Ad26- or MVA-based vaccine in the 
past.
4.
Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines 
or vaccine products (including any of the constituents of the study vaccines), including 
known allergy to chicken or egg protein and gentamicin.
5.
Presence of acute illness (this does not include minor illnesses such as diarrhea or mild 
upper respiratory tract infection) or temperature ≥38.0ºC on Day 1. Participants with 
such symptoms will be excluded from enrollment at that time but may be rescheduled 
for enrollment at a later date.
6.
HIV type 1 or type 2 infection, based on the medical history reported by the participant.
7.
Criterion modified per Amendment 1
7.1 Criterion modified per Amendment 2
7.2 Pregnant, breast-feeding, or planning to become pregnant while enrolled in this 
study until at least 3 months post Dose 1 vaccination, 28 days post Dose 2vaccination,
or 3 months post booster vaccination (Groups 5-6 only), whichever comes later.
8.
Major surgery (per the investigator’s judgment) within the 4 weeks prior to screening 
or planned major surgery during the study (from the start of screening onwards). 
Participants with planned surgical procedures to be conducted under local and 
loco-regional anesthesia may participate.
9.
Post-organ and/or stem cell transplant whether or not with chronic immunosuppressive 
therapy.
10.
Received any disallowed therapies as noted in Section 8 before the planned 
administration of Dose 1.
11.
Received an investigational drug or investigational vaccine or used an invasive 
investigational medical device within 3 months prior to screening, or current or planned 
participation in another clinical study during the study.
Note: Participation in an observational clinical study is allowed.

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12.
Criterion modified per Amendment 2
12.1 Received or plans to receive:
a.
Licensed live-attenuated vaccines within 28 days before or after planned 
administration of the first or second study vaccine or booster dose (Groups 5-6 
only);
b. Other licensed (not live) vaccines within 14 days before or after planned 
administration of the first or second study vaccine or booster dose (Groups 5-6 
only).
13.
Donation of a unit of blood within 12 weeks before Day 1 or plans to donate blood 
during participation in the study (from the start of screening onwards).
14.
Receipt of blood products within 4 months or immunoglobulins within 2 months prior 
to the planned administration of Dose 1 vaccination (Ad26.ZEBOV) and foreseen 
during participation in the study.
15.
Current or past abuse of alcohol, recreational or narcotic drugs, which in the 
investigator’s opinion would compromise the participant’s safety and/or compliance 
with the study procedures.
16.
Unable to communicate reliably with the investigator.
17.
Unlikely to adhere to the requirements of the study in the opinion of the investigator.
18.
Employee of the investigator or study site, with direct involvement in the proposed 
study or other studies under the direction of that investigator or study site, as well as 
family members of the employees or the investigator.
19.
Under legal guardianship or incapacitation.
20
History of an underlying clinically significant acute or chronic medical condition (eg, 
severe chronic obstructive pulmonary disease or clinically significant congestive heart 
failure, end-stage renal disease with or without dialysis, clinically unstable cardiac 
disease, Alzheimer’s disease, immune suppression, bleeding/clotting disorder, 
autoimmune disease, active malignancy, poorly controlled asthma, active tuberculosis, 
or other systemic infections) or physical examination findings for which, in the opinion 
of the investigator, participation would not be in the best interest of the participant (eg, 
compromise the well-being) or that could prevent, limit, or confound the 
protocol-specified assessments.
21
Criterion added per Amendment 2
Difficulty in taking blood samples.
NOTE: Investigators should ensure that all study enrollment criteria have been met at the end of 
screening. If a participant's clinical status changes (including receipt of additional medical records) 
after screening but before Dose 1 vaccination such that he or she no longer meets all eligibility 
criteria, then the participant should be excluded from further participation in the study. 

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4.3.
Prohibitions and Restrictions
Potential participants must be willing and able to adhere to the following prohibitions and 
restrictions during the course of the study to be eligible for participation:
1.
Women of childbearing potential must remain on an acceptable effective method of 
birth control consistent with local regulations regarding the use of birth control methods 
for participants in clinical studies (see inclusion criteria in Section 4.1) until at least 
3 months post Dose 1 vaccination or 28 days post Dose 2 vaccination or 3 months post 
booster vaccination (Groups 5-6 only), whichever comes later. If the social situation of 
a woman of childbearing potential changes (eg, woman who is not heterosexually active 
becomes active), she must begin a highly effective method of birth control, as described 
above in Section 4.1, until at least 3 months post Dose 1 vaccination or 28 days post
Dose 2 vaccination or 3 months post booster vaccination (Groups 5-6 only), whichever 
comes later.
Note: Prior to each study vaccine administration, a urine pregnancy test should be 
performed for women of childbearing potential.
2.
In case of a new Ebola outbreak: participants should not travel to an area with Ebola 
outbreak while enrolled in the study from the start of screening onwards until the 21-day 
post Dose 2/booster dose (Groups 5-6 only) visit. If applicable, any traveling to an area 
with Ebola outbreak should be documented in the electronic case report form (eCRF).
3.
Refer to Section 8 for details regarding prohibited and restricted therapy during the 
study.
4.
Agree to follow all requirements that must be met during the study as noted in the 
inclusion and exclusion criteria (eg, contraceptive requirements).
5.
STUDY VACCINE ALLOCATION AND BLINDING
Study Vaccine Allocation
Procedures for Randomization 
Central randomization will be implemented in this study. Participants will be randomly assigned 
to 1 of 4 vaccination groups for the main part of the study (Groups 1-4) and 1 of 2 groups for the 
Booster Cohort (Groups 5-6) based on a computer-generated randomization schedule prepared 
before the study by or under the supervision of the sponsor. The randomization will be balanced 
by using randomly permuted blocks. The IWRS will assign a unique code, which will dictate the 
study vaccine assignment and matching study vaccine kit for the participant. The requestor must 
use his or her own user identification and personal identification number when contacting the 
IWRS and will then give the relevant participant details to uniquely identify the participant.

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Blinding
The investigator will not be provided with randomization codes. The codes will be maintained 
within the IWRS, which has the functionality to allow the investigator to break the blind for an 
individual participant.
Data that may potentially unblind the study vaccine allocation (ie, antibodies to study vaccine, 
study vaccine preparation/accountability data, or other specific laboratory data) will be handled 
with special care to ensure that the site and sponsor personnel involved in the review and 
determination of causality of serious adverse events reported during the study will remain blinded 
until final database lock. This can include making special provisions, such as segregating the data 
in question from view by the investigators, clinical team, or others as appropriate until the time of 
database lock and unblinding. The pharmacy and preparation of study vaccine will be monitored 
by an independent study vaccine monitor (see Section 17.8).
Under normal circumstances, the blind should not be broken until all participants have completed 
the study and the database is locked. The investigator may in an emergency determine the identity 
of the study vaccine by contacting the IWRS. While the responsibility to break the code in 
emergency situations resides solely with the investigator, it is recommended that the investigator 
contacts the sponsor or its designee if possible to discuss the particular situation, before breaking 
the blind. Telephone contact with the sponsor or its designee will be available 24 hours per day, 
7 days per week. In the event the blind is broken, the sponsor must be informed as soon as possible.
The date, time, and reason for the unblinding must be documented by the IWRS. The 
documentation received from the IWRS indicating the code break must be retained with the 
participant's source documents in a secure manner.
In general, randomization codes will be disclosed fully only if the study is completed and the
clinical database is locked. However, for the primary analysis, the randomization codes and, if 
required, the translation of randomization codes into vaccination and control groups will be 
disclosed to authorized sponsor personnel involved in the analysis of the data. At the time of the 
primary analysis, the participants, the investigator(s) and study site personnel will remain blinded 
to individual participants’ study vaccine allocation.
If the randomization code is broken by the investigator or the study site personnel, the participant 
must discontinue further study vaccine administration and must be followed as appropriate (see 
Section 10.2 for details). If the randomization code is broken by the sponsor for safety reporting 
purposes, the participant should not discontinue further study vaccine administration and may 
remain in the study (if the randomization code is still blinded to the study site personnel and the 
participant).

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6.
DOSAGE AND ADMINISTRATION
An overview of the study vaccination schedule is provided in Section 3.1, Table 1. All participants 
will receive a vaccination, according to randomization, on Day 1, on Day 57, and on Day 177
(Groups 5-6 only) at the following dose levels:
-
Ad26.ZEBOV: 5x1010 vp, supplied in a single-use vial (0.5 mL extractable) (Groups 1, 2, 3, 
5);
-
MVA-BN-Filo: 1x108
Inf U, supplied in a single-use vial (0.5 mL extractable) 
(Groups 1, 2, 3, 5);
-
Placebo: 0.9% saline, 0.5 mL (Groups 4 and 6).
Blinding will be achieved by preparation of study vaccine by unblinded qualified study site 
personnel not involved in any other study-related procedure, and by the administration of study 
vaccine in a masked syringe by a blinded study vaccine administrator.
Ad26.ZEBOV and MVA-BN-Filo, or placebo, will be administered as 0.5-mL IM injections in 
the deltoid muscle. The injection site should be free from any injury, local skin condition, or other 
issue that might interfere with the evaluation of local reactions (eg, significant tattoo). In each 
participant, it is recommended that the second vaccination is administered in the opposite deltoid 
muscle from the first vaccination (unless the opposite arm has a condition that prevents evaluating 
the arm after injection) and it should be recorded in the eCRF in which arm the vaccination has 
been administered. The booster dose may be administered in either deltoid. No local or topical 
anesthetic will be used prior to the injection.
After each vaccination, participants will remain at the study site for at least 30 minutes for presence
of any acute reactions and solicited events, or longer if deemed necessary by the investigator (eg, in 
case of grade 3 adverse events).
As with any vaccine, allergic reactions following vaccination with the study vaccine are possible. 
Therefore, appropriate drugs and medical equipment to treat acute anaphylactic reactions must be 
immediately available and a medically qualified member of the study site personnel trained to 
recognize and treat anaphylaxis must be present at the study site during the entire vaccination 
procedure and postvaccination monitoring period.
The investigator must provide emergency care as needed for any participant who experiences a 
life-threatening event. All study sites will have facilities, equipment, and the ability to manage an 
anaphylactic reaction. If additional therapy is required, the investigator will arrange for transport 
to the closest appropriate facility for continuing care.
The Site Investigational Product Procedures Manual specifies the maximum time that will be 
allowed between preparation and administration of the study vaccine. 

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6.1.
Criteria for Postponement of Vaccination
A participant will not be given any study vaccine if he or she experiences any of the following 
events at the scheduled time for vaccination: 
-
Acute illness at the time of vaccination (this does not include minor illnesses such as diarrhea 
or mild upper respiratory tract infection);
-
Fever (body temperature ≥38.0°C) at the time of vaccination.
Participants experiencing any of the events described above may be vaccinated up to 10 days 
beyond the window allowed for the scheduled vaccination, or be withdrawn from that vaccination 
at the discretion of the investigator and after consultation with the sponsor.
Note: In case Dose 2 or booster dose vaccination is postponed, the timing of the post Dose 2 or 
post booster dose visits will be planned relative to the actual vaccination day.
6.2.
Contraindications to Second Vaccination
A participant will not be given the Dose 2 or booster dose vaccination if he or she experiences any 
of the following events at any time after the Dose 1 vaccination: 
1. Anaphylaxis clearly attributable to vaccination with study vaccine; OR
2. Generalized urticaria within 72 hours of vaccination considered to be related to study vaccine; 
OR
3. A serious adverse event considered to be related to study vaccine; OR
4. Injection site ulceration, abscess, or necrosis considered to be related to study vaccine; OR
5. Any other safety concern threatening the participant’s safety.
Participants experiencing any of the events described above must not receive any further study 
vaccine but should continue be monitored for safety and for immunogenicity according to the
protocol if this does not result in safety risks for the participant.
7.
STUDY VACCINE COMPLIANCE
Study vaccine will be administered as an IM injection by blinded qualified study site personnel at 
the study site. Details of each administration will be recorded in the eCRF (including date and time 
of injection and arm used for injection). For blinding procedures, see Section 5.
8.
PRESTUDY AND CONCOMITANT THERAPY
Prestudy-specific 
therapies
such 
as 
analgesic/antipyretic 
medications,
nonsteroidal 
anti-inflammatory 
drugs,
vaccines,
and 
immunomodulators/suppressors 
(eg, 
cancer 
chemotherapeutic agents, systemic corticosteroids) administered up to 30 days prior to the first 
dose of study vaccine and previous vaccinia/smallpox vaccination at any time prior to study entry
must be recorded in the eCRF at screening.

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Concomitant therapies such as analgesic/antipyretic medications, nonsteroidal anti-inflammatory 
drugs, vaccines, and immunomodulators/suppressors (eg, cancer chemotherapeutics, systemic 
corticosteroids) must be recorded from Dose 1 vaccination until 28 days post Dose 1 vaccination, 
from Dose 2 vaccination until 28 days post Dose 2 vaccination, and from the booster dose 
vaccination until 28 days post booster dose (Groups 5-6 only). All other concomitant therapies 
should also be recorded beyond these time frames until the end of the study if administered in 
conjunction with serious adverse events (refer to Section 12.3.2).
Use of any experimental medication (including experimental vaccines other than the study 
vaccine) within 3 months prior to screening and during the study is not allowed.
Information on concomitant use of herbal supplements or vitamins will not be collected.
All women of childbearing potential must use adequate birth control measures prior to 
randomization as described in Section 4.1.
Participants are allowed to receive all routine immunizations according to local schedules, taking 
into consideration the following restrictions. These routine immunizations should not be 
administered at least 14 days before (or at least 14 days after) administration of any study vaccine
to avoid any potential interference in efficacy of the routine immunizations or the interpretation of 
immune responses to study vaccines, as well as to avoid potential confusion with regard to 
attribution of adverse events. Vaccination with licensed live-attenuated vaccines within 28 days
before or after administration of a study vaccine is prohibited. However, if a vaccine is indicated 
in a post-exposure setting (eg, rabies or tetanus), it must take priority over the study vaccine. 
Chronic or recurrent use of immunomodulators/suppressors, eg, cancer chemotherapeutic agents, 
systemic corticosteroids is prohibited during the study and within 30 days before the planned 
administration of the first dose of study vaccine. Note: Ocular, topical, or inhaled steroids are 
allowed.
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in 
which prohibited therapies are administered. Prohibited therapies will be captured as protocol 
deviations.
9.
STUDY EVALUATIONS
9.1.
Study Procedures
9.1.1.
Overview
The TIME AND EVENTS SCHEDULE summarizes the frequency and timing of all 
measurements and evaluations applicable to this study.
Visit windows are provided in the TIME AND EVENTS SCHEDULE. In case the Dose 2 or 
booster dose vaccination is postponed, the timing of the post Dose 2 and booster dose visits will 
be determined relative to the actual day of vaccination. The participant should be encouraged to 
come within these windows.

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Additional urine pregnancy tests may be performed, as determined necessary by the investigator 
or required by local regulation, to establish the absence of pregnancy at any time during 
participation in the study.
The total blood volume to be collected from each participant in the immunogenicity subset will be
approximately 25.5 mL. For the Booster Cohort, approximately 68 mL total blood volume will be 
collected (refer to Section 9.2).
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples.
9.1.2.
Screening, Vaccination, Postvaccination Visits, and Follow-up
At baseline (Day 1, day of Dose 1 vaccination) and after signing and dating the ICF (see 
Section 16.2.3), screening assessments will be performed as indicated in the TIME AND EVENTS 
SCHEDULE. If needed, the screening activities may be split over multiple visits, with a maximum 
of up to 28 days between signing of the ICF and Dose 1 vaccination.
Only participants complying with the criteria specified in Section 4 will be included in the study. 
The overall eligibility of the potential participant will be assessed once all required evaluations, 
including inclusion and exclusion criteria, are available. If rescreening is required, all screening 
procedures should be repeated. Study participants who qualify for inclusion will be enrolled and 
will receive Dose 1 vaccination on the same day.
The investigator should ensure that all study enrollment criteria have been met at the end of
screening. If a participant's clinical status changes (including receipt of additional medical records) 
after screening but before Dose 1 vaccination such that he or she no longer meets all eligibility
criteria, then the participant should be excluded from further participation in the study. 
Eligible participants will be allocated to a vaccination group as described in Section 5. Before each 
vaccination, a urine pregnancy test (only for women of childbearing potential), a full physical 
examination (before Dose 1, Day 1) or an abbreviated, symptom-directed physical examination 
(before Dose 2 and before the booster dose [Groups 5-6 only]), and measurement of vital signs 
will be performed as indicated by the investigator. 
Participants will be vaccinated as described in Section 6. After each vaccination, participants will 
remain under observation at the study site for at least 30 minutes for presence of any acute reactions 
and solicited events, or longer if deemed necessary by the investigator (eg, in case of grade 3 
adverse events). Solicited and unsolicited adverse events emerging during the observation period 
will be recorded in the eCRF. 
Upon discharge from the study site, participants will receive a thermometer (to measure body
temperature), a ruler (to measure local injection site reactions), and a participant diary to record 
body temperature and symptoms of solicited local (at injection site) and systemic adverse events
and will be trained on how to collect this information. The participants will record symptoms of 

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solicited local and systemic adverse events in the diary in the evening after each vaccination and 
then daily for the next 7 days. The diary cards will be reviewed by study site personnel at the 
Day 57 visit (before Dose 2 vaccination), at the Day 78 visit, and at the Day 184 visit (Groups 5-
6 only).
All adverse events and special reporting situations, whether serious or nonserious, that are related 
to study-related procedures or to non-investigational (concomitant) sponsor products, and 
pregnancy (if applicable), will be reported from the time a signed and dated ICF is obtained 
onwards.
Other serious adverse events and special reporting situations will be reported from first dose of 
study vaccine until the end of the study.
Other nonserious adverse events and special reporting situations (ie, not related to study-related 
procedures or non-investigational [concomitant] sponsor products) will be reported from first dose
of study vaccine until 28 days after first dose of study vaccine, from the second dose of study
vaccine until 28 days thereafter, and from the booster dose until 28 days thereafter (Groups 5-6 
only). Participants will be asked about the occurrence of unsolicited adverse events at the Day 57 
visit (before Dose 2 vaccination), at the Day 78 visit, at the Day 177, 184 and 198 visits (Group 5-
6 only), and by means of a telephone call at Days 29 and 85, and at Day 205 (Groups 5-6 only).
Unsolicited adverse events with the onset date outside the time frame defined above (>28 days 
after previous study vaccination), which are ongoing on the day of the subsequent vaccination, 
should be recorded in the eCRF Adverse Event page.
Clinically relevant medical events occurring between signing of the ICF and first vaccination will 
be collected on the eCRF Medical History page as pre-existing conditions.
Participants will come to the study site 21 days post Dose 2 vaccination for safety and 
immunogenicity assessments. Participants in Groups 5 and 6 will also return to the site 7 and 
21 days post booster dose vaccination for safety and immunogenicity assessments.  
Participants in Groups 1-4 will be contacted via a telephone call 6 months post Dose 2 (ie, on 
Day 237 post Dose 1 vaccination) to assess safety. Participants in Groups 5-6 will not be contacted 
at that time but will return to the site 6 and 12 months post booster dose vaccination for long term 
immunogenicity follow-up.
Refer to Section 9.2 for details on the immunogenicity evaluations and Section 9.3 for the safety 
evaluations.
9.2.
Immunogenicity Evaluations
Blood samples (8.5 mL) for humoral immunogenicity assessments (ie, analysis of antibodies 
binding to EBOV GP, using ELISA [EU/mL]) will be collected from participants in the 
immunogenicity subset and Groups 5-6 at the time points indicated in the TIME AND EVENTS 
SCHEDULE.

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For Groups 5-6 only, an assessment of neutralizing antibodies against the Ad26 vector will be 
performed at baseline (pre Dose 1), pre booster vaccination (Day 177), and at 21 days post booster 
vaccination (Day 198). 
Sample collection and processing will be performed by the study site personnel according to 
current versions of approved standard operating procedures. The laboratory manual contains 
further details regarding the collection, handling, labeling, storage and shipment of blood samples 
to the laboratory.
The analysis of the immunogenicity samples will be done at a specialized laboratory.
9.3.
Safety Evaluations
9.3.1.
Safety Assessments
The investigators, together with the sponsor’s medical monitor, will be responsible for the safety 
monitoring of the study, and will halt vaccination of further participants in case any of the 
pre-specified pausing rules described in Section 9.3.2 have been met.
The sponsor has mechanisms, teams, and procedures in place to systematically analyze the safety 
profile of its investigational products during clinical development, including a multidisciplinary 
SMT dedicated to the Ebola vaccines development. SMTs are product-based, cross-functional 
collaborative teams responsible for review, assessment, and evaluation of medical safety data 
arising from any source throughout the Product Lifecycle. The SMT performs assessments in order 
to identify changes in safety profiles or potential safety signals. Based on these safety evaluations, 
the SMT will determine the appropriate safety-related actions to be taken with respect to the study 
vaccine based on its benefit-risk profile for participants in clinical studies, including 
VAC52150EBL3004.
Additionally, the following procedures will be in place to identify timely and assess in due time 
any relevant safety information (serious adverse events or a trend in unsolicited adverse events) 
which may emerge: 

An assessment (within 24 hours) by a blinded study physician of a serious adverse event
reported by the study site (see Section 12.3.2 for more details).

A medical evaluation of serious adverse events reported by a blinded study physician to detect 
timely any relevant trend in the safety data (number, severity, and seriousness of serious
adverse events).

An escalation of a suspected serious adverse event or a safety signal emerging to the SMT.
Any clinically relevant changes occurring during the study must be recorded in the eCRF Adverse 
Event page.

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Any clinically significant abnormalities (including those persisting at the end of the study/early 
withdrawal) will be followed by the investigator until resolution or until a clinically stable endpoint
is reached.
The study will include the following evaluations of safety and reactogenicity at the time points 
provided in the TIME AND EVENTS SCHEDULE:
Adverse Events
All adverse events will be reported as specified in Section 12.3.1.
Solicited Adverse Events
After each vaccination, participants will remain under observation at the study site for at least 
30 minutes for presence of any acute reactions and solicited events, or longer if deemed necessary 
by the investigator. Upon discharge from the study site, participants will be provided with a diary 
and instructions on how to complete the diary: symptoms of solicited local and systemic adverse 
events will be collected in the diary in the evening after each vaccination and then daily for the 
next 7 days. The participants will complete their diary cards at home and these will be reviewed 
by study site personnel at the Day 57 visit (before Dose 2 vaccination) and at the Day 78 visit, and 
at the Day 184 visit (Groups 5-6 only). Diary information will be transcribed by the study 
personnel in the diary eCRF pages. Once a solicited symptom from a diary is considered to be of 
severity grade 1 or above, it will be referred to as a solicited adverse event.
Solicited Injection Site (Local) Adverse Events
Participants will be asked to note in the diary occurrences of pain/tenderness, erythema,
induration/swelling, and pruritus at the study vaccine injection site daily for 7 days postvaccination 
(day of vaccination and the subsequent 7 days). The extent (largest diameter) of any erythema, and 
induration/swelling should be measured (using the ruler supplied) and recorded daily. 
Solicited Systemic Adverse Events
Participants will be instructed on how to record daily temperature using a thermometer provided 
for home use. The (oral) body temperature of the participant should be recorded in the diary in the 
evening of the day of vaccination, and then daily for the next 7 days approximately at the same 
time each day. If more than one measurement is made on any given day, the highest temperature 
of that day will be used in the eCRF.
Fever is defined as endogenous elevation of body temperature ≥38.0°C, as recorded in at least one 
measurement.5
Participants will also be instructed on how to note daily in the diary symptoms for 7 days 
postvaccination (day of vaccination and the subsequent 7 days) of the following events: fatigue, 
headache, nausea, myalgia, arthralgia, chills, and fever.

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Physical Examination 
A full physical examination (excluding genito-urinary system), including height and body weight, 
will be carried out at screening (Day 1). At other visits, an abbreviated, symptom-directed 
examination will be performed based on any clinically relevant issues, clinically relevant 
symptoms and medical history. The symptom-directed physical examination may be repeated if 
deemed necessary by the investigator. Physical examinations will be performed by the investigator 
or by a designated medically-trained clinician. 
Vital Signs 
Blood pressure, pulse/heart rate and oral body temperature will be assessed before each 
vaccination and at other visits as indicated in the TIME AND EVENTS SCHEDULE. 
Blood pressure and pulse/heart rate measurements will be assessed in supine position with a 
completely automated device. Manual techniques will be used only if an automated device is not 
available. 
Supine blood pressure and pulse/heart rate measurements should be preceded by at least 5 minutes 
of rest in a quiet setting without distractions (eg, television, cell phones).
9.3.2.
Study Vaccination Pausing Rules
The investigators and the sponsor’s medical monitor will review the safety of enrolled participants 
on an ongoing basis and will halt vaccination of further participants in case any of the pre-specified 
pausing rules described in this section are met. The sponsor’s medical monitor will be involved in 
all discussions and decisions.
The occurrence of any of the following events will lead to pause in further study vaccination.
1.
Death of a participant, considered related to study vaccine or if the causal relationship to the 
study vaccine cannot be excluded; OR
2.
One or more participants experience a life-threatening or serious adverse event (solicited or 
unsolicited) that is determined to be related to study vaccine; OR
3.
One or more participants experience anaphylaxis or generalized urticaria within 24 hours of 
vaccination, clearly not attributable to other causes than vaccination with study vaccine.
All sites will be notified immediately in case of a study pause. The clinical sites will be allowed to 
resume activities upon receipt of a written notification from the sponsor. These communications 
will be forwarded by the investigator to the Institutional Review Board (IRB)/Independent Ethics 
Committee (IEC) and by the sponsor to the relevant health authorities, according to local standards 
and regulations.

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9.4.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the eCRF or laboratory 
requisition form. 
Refer to the TIME AND EVENTS SCHEDULE for the timing and frequency of all sample 
collections.
Instructions for the collection, handling, labeling, storage, and shipment of samples are found in 
the laboratory manual that will be provided. Collection, handling, storage, and shipment of samples 
must be under the specified, and where applicable, controlled temperature conditions as indicated 
in the laboratory manual.
10.
PARTICIPANT COMPLETION/DISCONTINUATION OF STUDY VACCINE/ 
WITHDRAWAL FROM THE STUDY
10.1.
Completion
A participant in Groups 1-4 will be considered to have completed the study if he or she has 
completed assessments at the Day 237 time point (ie, 6-months post Dose 2). A participant in 
Groups 5-6 will be considered to have completed the study if he or she has completed assessments 
at the Day 537 time point (ie, 12-months post booster dose).
10.2.
Discontinuation of Study Vaccine/Withdrawal From the Study
Discontinuation of Study Vaccine
A participant will not be automatically withdrawn from the study if he or she has to discontinue 
study vaccine before the end of the vaccine regimen.
A participant's study vaccine (Dose 1, Dose 2, or booster dose) may be discontinued at the 
discretion of the investigator and after consultation with the sponsor for any of the events in 
Section 6.1.
A participant’s study vaccine should be permanently discontinued if:

The investigator believes that for safety or reactogenicity reasons (eg, adverse event) it is in 
the best interest of the participant to discontinue study vaccine;

The participant becomes pregnant;

Confirmed EVD;

The participant experiences any of the events described in Section 6.2;

The randomization code is broken by the investigator or the study site personnel.
Participants meeting any of the reasons listed above must not receive any further study vaccine but 
should continue to be monitored for safety and immunogenicity according to the protocol if this 
does not result in safety risks for the participant. In case of early discontinuation of study vaccine
due to an adverse event, the investigator will collect all information relevant to the adverse event 

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and safety of the participant, and will follow the participant to resolution, or until reaching a 
clinically stable endpoint.
Withdrawal From the Study
Each participant has the right to withdraw from the study at any time for any reason without 
affecting the right to treatment by the investigator. The investigator should make an attempt to 
contact participants who did not return for scheduled visits or follow-up. Although the participant 
is not obliged to give reason(s) for withdrawing prematurely, the investigator should make a 
reasonable effort to ascertain the reason(s) while fully respecting the participant’s rights. 
A participant will be withdrawn from the study for any of the following reasons:

Lost to follow-up

Withdrawal of consent

Death

Repeated failure to comply with protocol requirements

Decision by the sponsor or the investigator to stop or cancel the study

Decision by local regulatory authorities or IRB/IEC to stop or cancel the study
If a participant is lost to follow-up, every reasonable effort must be made by the study site 
personnel to contact the participant and determine the reason for discontinuation/withdrawal. The 
measures taken to follow up must be documented.
When a participant withdraws before completing the study, the reason for withdrawal is to be 
documented in the eCRF and in the source document. Study vaccine assigned to the withdrawn 
participant may not be assigned to another participant. Participants who withdraw will be replaced, 
as long as the participant has not been vaccinated yet.
If a participant withdraws early from the study, early withdrawal assessments should be obtained 
per the assessments for the 21-day post Dose 2 visit, with the exception of the immunogenicity 
assessments, if applicable. A participant who wishes to withdraw consent from participation in the 
study will be offered an optional visit for safety follow-up (before formal withdrawal of consent), 
but the participant has the right to refuse.
11.
STATISTICAL METHODS
Statistical analysis will be done by the sponsor or under the authority of the sponsor. A general 
description of the statistical methods to be used to analyze the immunogenicity and safety data is 
outlined below. Specific details will be provided in the Statistical Analysis Plan (SAP).
For the main part of the study (Groups 1-4), the primary safety and immunogenicity analyses will 
be conducted when all participants in Groups 1-4 have completed the 28-day post Dose 2 time 
point or discontinued earlier, and the database is locked. Only sponsor personnel not involved in 
the review and determination of causality of serious adverse events reported during the study will 

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be unblinded to Groups 1-4 at this time point. Investigator, study site personnel (except for those 
with primary responsibility for study vaccine preparation and dispensing), and participants will 
remain blinded to the study vaccine allocation until the last participant in Groups 1-4 completes 
the 6-month post Dose 2 time point (ie, Day 237, last study related visit) or discontinues earlier 
(and the database is locked). An interim analysis will be performed when all participants in Groups 
1-4 have completed the 6-month post Dose 2 visit, ie, the last study-related visit (or discontinue 
earlier), and the database has been locked.
For the Booster Cohort (Groups 5-6), an interim analysis will be performed when all participants 
in Groups 5-6 have completed the 28-day post booster dose time point (or discontinued earlier). 
This analysis, based on the corresponding locked database, will include all available data 
(including safety and 21-day post booster dose immunogenicity data) up to the cut off. Only 
sponsor personnel not involved in the review and determination of causality of serious adverse 
events reported during the study will be unblinded to Groups 5-6 at this time point. Investigators, 
study site personnel (except for those with primary responsibility for study vaccine preparation 
and dispensing), and participants will remain blinded to the study vaccine allocation until the 
database is locked for the final analysis.
The final analysis will be conducted when all participants in the study have completed the last 
study-related visit or have discontinued earlier.
A planned analysis may be combined with the subsequent analysis, if deemed necessary (eg, when 
the dates of 2 planned database locks are very close).
11.1.
Analysis Sets
Full Analysis Set: The full analysis set will include all participants with at least one study vaccine
administration documented. Participants will be analyzed according to the study vaccine they 
actually received.
Per Protocol Analysis Set: The per protocol analysis set will include all randomized and 
vaccinated participants, who received both Dose 1 and Dose 2 vaccinations (administered within 
the protocol-defined window), had at least one postvaccination (ie, after the date of vaccination)
evaluable immunogenicity sample, and had no major protocol deviations that may influence the 
immune response. The per protocol analysis set will be defined for participants included in the 
immunogenicity subset. Similarly, the per protocol analysis set for the Booster Cohort (Groups 5-
6) will include all vaccinated participants, who received Dose 1, Dose 2, and the booster 
vaccination (ie, both Dose 2 and Ad26.ZEBOV booster vaccination within the protocol-defined 
window), had at least one postvaccination (ie, after the date of vaccination) evaluable 
immunogenicity sample, and had no major protocol deviations that may influence the immune 
response.

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11.2.
Sample Size Determination
The following assumptions are used in the sample size determination:
-
A standard deviation of 0.55 on the log10 scale (binding antibody levels against the EBOV GP 
using ELISA [EU/mL] 21 days post Dose 2 vaccination, following Dose 1 on Day 1 and 
Dose 2 on Day 57). This standard deviation is obtained by adding 10% to the maximum 
observed standard deviation at 56 days post Dose 1 vaccination in the Phase 2/3 studies and 
will also ensure adequate power in demonstrating lot-to-lot consistency at 56 days post Dose 1
vaccination (ie, secondary objective).
-
An overall 5% dropout rate.
In addition, specific assumptions are made for the equivalence testing for the primary and 
secondary objective:
Assumptions specific to equivalence testing:
-
A relative difference of 10% in GMC of binding antibodies between groups (ie, Groups 1 
to 3). This is expressed as GMC(1) = 0.9 x GMC(3), where GMC(1), GMC(2), and GMC(3) denote 
the ordered GMC. This relative difference is based on both the process variability in vp content 
of the Ad26.ZEBOV lots and Inf U content of MVA-BN-Filo lots. A linear relationship 
between log10-transformed vaccine contents (ie, Ad26.ZEBOV and MVA-BN-Filo) and 
log10-transformed GMC of binding antibodies (ELISA GMC) was assumed. 
-
Clinical equivalence limits on the GMC ratio are 0.5 and 2.0.
Under the above assumptions, a total of 144 participants per group receiving Ad26.ZEBOV as 
Dose 1 and MVA-BN-Filo as Dose 2, would yield an overall power of at least 90% to show 
immunogenic equivalence of the 3 groups (Groups 1 to 3) 21 days post Dose 2 vaccination 
(ie, with 96.55% power for each of the 3 pairwise comparisons [ie, Groups 1 vs 2, 1 vs 3 and 
2 vs 3]). PASS 11 is used for the sample calculations. In order to enlarge the safety database, the 
total number per group was increased to 234 (ie, additional 90 participants per group for safety 
only). 
A randomization ratio of 6:6:6:1 (Group 1:Group 2:Group 3:Group 4) yields an overall sample 
size of 741 participants, with 234 participants per group (in Groups 1 to 3) receiving 
Ad26.ZEBOV and MVA-BN-Filo, and 39 participants receiving placebo (Group 4).
Due to the recent (on 11-March-2020) WHO declared COVID-19 pandemic, a potential higher 
dropout rate (ie, higher than 5%) may occur. In addition, some participants in the immunogenicity 
subset may be excluded from primary immunogenicity equivalence testing because of:

Participant not receiving Dose 2; OR

Participant receiving Dose 2 outside the protocol defined window; OR

Participant not attending the 21-day post Dose 2 visit; OR

Participant attending the 21-day post Dose 2 visit outside the protocol-defined window.

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To mitigate these issues, additional participants may be recruited in the immunogenicity subset.
Shortly after participants received Dose 1 vaccination, ‘stay-at-home’ orders were imposed in the 
areas where the sites were located and approximately 22% of participants did not return to the site 
within the protocol defined windows (±3 days) for Dose 2 administration. 
Examination 
of 
the 
immunogenicity 
data 
from 
studies
(VAC52150EBL2001 
and 
VAC52150EBL2002) in which Dose 2 was administered at intervals ≥56 days reveals that 
although there appears to be trend of increasing GMCs with increasing intervals between Dose 1 
and Dose 2, the variability (standard deviation) of the immune responses (binding antibody levels 
against the EBOV GP using ELISA [EU/mL]) remains stable and in line with the currently 
assumed standard deviation of 0.55 (on the log10-scale). Assuming that the delayed Dose 2 
administration will be randomly distributed among the groups (ie, Groups 1-4), widening the 
acceptable time frame to administer Dose 2 by increasing the upper limit of the window to 28 days
(ie, Day 57+28 days) is not expected to adversely affect the primary and secondary objectives of 
the study. With the widened window, the number of additional participants necessary to maintain 
approximately 90% power to test the primary and secondary hypotheses will be reduced.
Approximately 60 participants will be randomized in a 5:1 active:placebo ratio (Group 5:Group 6), 
which will provide a reasonable estimation of the humoral immune response to a booster dose.
11.3.
Immunogenicity Analyses
Descriptive statistics (including geometric means with their corresponding 95% CIs, median, 
interquartile range, minimum, maximum, as applicable) will be calculated for continuous 
immunologic parameters at each time point. Graphical representations of immunologic parameters 
will be prepared, as applicable. Frequency tabulations will be calculated for discrete (qualitative) 
immunologic parameters at each time point.
To assess the primary objective, each pairwise comparison (ie, Groups 1 vs 2, 1 vs 3, 2 vs 3) of
the anti-EBOV GP binding antibody responses 21 days post Dose 2 vaccination with 
MVA-BN-Filo will be based on ratios of the GMC with corresponding 95% CI. Equivalence of 
any 2 groups will be shown if the 95% CI of the estimated GMC ratio lies entirely within 0.5 and 
2.0. Lot-to-lot consistency is accomplished if equivalence is shown for all 3 pairwise comparisons. 
For the secondary objective, each pairwise comparison of the anti-EBOV GP binding antibody 
responses 56 days post Dose 1 vaccination with Ad26.ZEBOV will be based on ratios of the GMCs 
with corresponding 95% CI. Equivalence of any 2 groups will be shown if the 95% CI of the 
estimated GMC ratio lies entirely within 0.5 and 2.0. Lot-to-lot consistency (for Ad26.ZEBOV) is 
accomplished if equivalence is shown for all 3 pairwise comparisons. 
As a sensitivity analyses, both the primary and secondary hypotheses of equivalence will also be 
tested based on data of participants who received the second vaccination within the original 
window (±3 days) around the Day 57 visit.

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11.4.
Safety Analysis
No formal statistical testing of safety data is planned. All the participants who received at least 
1 dose of the study vaccine will be included in the full analysis set. The reporting of the categorical 
safety data will include the incidence, severity, relatedness, and type of adverse events. Continuous 
safety parameters will be analyzed descriptively (showing the mean, standard deviation, median,
and quartiles [Q1 and Q3]).
Baseline for all vital signs and physical examinations will be defined as the last evaluation done
before Dose 1 vaccination.
Adverse Events (Including Reactogenicity)
The verbatim terms used in the eCRF by investigators to identify adverse events will be coded 
using the Medical Dictionary for Regulatory Activities (MedDRA). For each adverse event, the 
percentage of participants who experience at least 1 occurrence of the given event will be 
summarized by group. In addition, comparisons between groups will be provided if appropriate. 
All reported adverse events and events-related diary information (solicited local at injection site 
and systemic, and unsolicited) with onset within 28 days post Dose 1, Dose 2 or booster dose
vaccination (ie, treatment-emergent adverse events) will be included in the analysis. For each 
adverse event, the number and percentage of participants who experience at least 1 occurrence of 
the given event will be summarized by vaccination group.
Summaries, listings, datasets, or participant narratives may be provided, as appropriate, for those 
participants who die, who discontinue study vaccine due to an adverse event, or who experience a 
severe or a serious adverse event.
Solicited local (at injection site) and systemic adverse events will be summarized descriptively. 
The overall frequencies per vaccine group as well as frequencies according to severity and duration 
will be calculated for solicited adverse events. In addition, the number and percentages of 
participants with at least one solicited local (at injection site) or systemic adverse event will be 
presented. Frequencies of unsolicited adverse events, separately for all and vaccination-related 
only, will be presented by System Organ Class and preferred term, while those of solicited adverse 
events will be presented only by preferred term.
Vital Signs
Descriptive statistics of blood pressure (systolic and diastolic; supine), pulse/heart rate, and oral 
temperature will be summarized. The percentage of participants with values beyond clinically 
important limits will be summarized.
Physical Examination
Physical examination findings will be listed.

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12.
ADVERSE EVENT REPORTING
Timely, accurate, and complete reporting and analysis of safety information from clinical studies 
are crucial for the protection of participants, 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.
Method of Detecting Adverse Events and Serious Adverse Events
Care will be taken not to introduce bias when detecting adverse events or serious adverse events. 
Open-ended and nonleading verbal questioning of the participant is the preferred method to inquire 
about adverse event occurrence.
Solicited Adverse Events
Solicited adverse events are predefined local (at the injection site) and systemic events for which 
the participant is specifically questioned and which are noted by participants in their diary (see 
Section 9.1.2).
Unsolicited Adverse Events
Unsolicited adverse events are all adverse events for which the participant is not specifically 
questioned in the participant diary (see Section 9.1.2).
12.1.
Definitions
12.1.1.
Adverse Event Definitions and Classifications
Adverse Event
An adverse event is any untoward medical occurrence in a clinical study participant administered 
a medicinal (investigational or non-investigational) product. An adverse event does not necessarily 
have a causal relationship with the study vaccine. An adverse event can therefore be any 
unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally 
associated with the use of a medicinal (investigational or non-investigational) product, whether or 
not related to that medicinal (investigational or non-investigational) product. (Definition per 
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use [ICH])
This includes any occurrence that is new in onset or aggravated in severity or frequency from the 
baseline condition, or abnormal results of diagnostic procedures.
Note: For time period of sponsor’s adverse event collection, see Section 12.3.1.

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Serious Adverse Event
A serious adverse event based on ICH and European Union 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 participant 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 in-patient 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 participant or may 
require intervention to prevent one of the other outcomes listed in the definition above. These 
should usually be considered serious.
If a serious and unexpected adverse event occurs for which there is evidence suggesting a causal 
relationship between the study vaccine and the event (eg, death from anaphylaxis), the event must 
be reported as a 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 Ad26.ZEBOV, MVA-BN-Filo, the expectedness of an 
adverse event will be determined by whether or not it is listed in the IB. 
Adverse Event Associated With the Use of the Study Vaccine
An adverse event is considered associated with the use of the study vaccine if the attribution is
related 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 diseases, concomitant therapies). This applies to all adverse 
events, whether serious or nonserious.
Causality of adverse events should be assessed by the investigator based on the following:
Related: there is a reasonable possibility that the study vaccine contributed to the adverse event.

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Unrelated: there is no suspicion that there is a relationship between the study vaccine and the 
adverse event; there are other more likely causes and administration of the study vaccine is not 
suspected to have contributed to the adverse event.
By definition, all solicited adverse events at the injection site (local) will be considered related to 
the study vaccine administration.
12.1.3.
Severity Criteria
All adverse events will be coded for severity using the toxicity grading tables in Attachment 1. For 
adverse events not identified in the table, the following guidelines will apply:
Mild
Grade 1
Symptoms causing no or minimal interference with usual social and 
functional activities
Moderate
Grade 2
Symptoms causing greater than minimal interference with usual 
social and functional activities
Severe
Grade 3
Symptoms causing inability to perform usual social and functional 
activities
The investigator should use clinical judgment in assessing the severity of events not directly 
experienced by the participant.
12.2.
Special Reporting Situations
Safety events of interest on a sponsor study vaccine that may require expedited reporting or safety 
evaluation include, but are not limited to:

Overdose of a sponsor study vaccine

Accidental or occupational exposure to a sponsor study vaccine

Medication error involving a sponsor product (with or without participant exposure to the 
sponsor study vaccine, eg, name confusion)

Suspected abuse/misuse of a sponsor study vaccine

Exposure to a sponsor study vaccine from breast-feeding
Special reporting situations should be recorded in the eCRF. Any special reporting situation that 
meets the criteria of a serious adverse event should be recorded in the serious adverse event page 
of the eCRF.
12.3.
Procedures
12.3.1.
All Adverse Events
Solicited adverse events will be recorded in a diary for each vaccination from the moment of 
vaccination until 7 days post each vaccination. 

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All adverse events and special reporting situations, whether serious or nonserious, that are related 
to study-related procedures or to non-investigational (concomitant) sponsor products, and 
pregnancy (if applicable), will be reported from the time a signed and dated ICF is obtained 
onwards.
Other serious adverse events and special reporting situations will be reported from first dose of 
study vaccine until the end of the study.
Other nonserious adverse events and special reporting situations will be reported from first dose 
of study vaccine until 28 days after first dose of study vaccine, from the second dose of study
vaccine until 28 days thereafter, and from the booster dose until 28 days thereafter (Groups 5-6 
only). 
Unsolicited adverse events with the onset date outside the time frame defined above (>28 days 
after previous study vaccination), which are ongoing on the day of the subsequent vaccination, 
should be recorded on the eCRF Adverse Event page.
Clinically relevant medical events occurring between signing of ICF and first vaccination will be 
collected on the eCRF Medical History page as pre-existing conditions.
The sponsor will evaluate any safety information that is spontaneously reported by an investigator 
beyond the time frame specified in the protocol.
The investigator will monitor and analyze the study data including all adverse event data as they 
become available and will make determinations regarding the severity of the adverse experiences 
and their relation to study vaccine. All adverse events will be deemed related to study vaccine or 
unrelated to study vaccine, according to Section 12.1.2. 
The investigator or clinical designee must review both post-injection reactogenicity and other 
adverse event eCRFs to insure the prompt and complete identification of all events that require 
expedited reporting as serious adverse events, invoke pausing rules or are other serious and 
unexpected events.
All adverse events, regardless of seriousness, severity, or presumed relationship to study vaccine, 
must be recorded using medical terminology in the source document and the eCRF. Whenever 
possible, diagnoses should be given when signs and symptoms are due to a common etiology 
(eg, cough, runny nose, sneezing, sore throat, and head congestion should be reported as "upper 
respiratory infection"). Investigators must record in the eCRF their opinion concerning the 
relationship of the adverse event to study therapy. All measures required for adverse event 
management must be recorded in the source document and reported according to sponsor 
instructions.
The sponsor assumes responsibility for appropriate reporting of adverse events to the regulatory 
authorities. The sponsor will also report all SUSARs to the investigator (and the head of the 
investigational institute where required). The investigator (or sponsor where required) must report 
SUSARs to the appropriate IEC/IRB that approved the protocol unless otherwise required and 

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documented by the IEC/IRB. A SUSAR will be reported to regulatory authorities unblinded. 
Participating investigators and IEC/IRB will receive a blinded SUSAR summary, unless otherwise 
specified.
Participants will be provided with a "wallet (study) card" and instructed to carry this card with 
them for the duration of the study indicating the following:

Study number

Statement, in the local language(s), that the participant is participating in a clinical study

Investigator's name and 24-hour contact telephone number

Local sponsor's name and 24-hour contact telephone number (for medical staff only)

Study site number

Participant number

Any other information that is required to do an emergency breaking of the blind

Ebola prevention counseling
12.3.2.
Serious Adverse Events
All serious adverse events occurring during the study must be reported to the appropriate sponsor 
contact person by study site personnel within 24 hours of their knowledge of the event.
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 transmitted electronically or 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 participant's participation in the study, must be followed until any of 
the following occurs:

The event resolves.

The event stabilizes.

The event returns to baseline, if a baseline value/status is available.

The event can be attributed to agents other than the study vaccine or to factors unrelated to 
study conduct.

It becomes unlikely that any additional information can be obtained (participant 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 

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during the course of a participant'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 eCRF). 
Note: Hospitalizations that were planned between signing of the ICF and first vaccination, 
and where the underlying condition for which the hospitalization was planned has not 
worsened, will not be considered serious adverse events. Any adverse event that results in a 
prolongation of the originally planned hospitalization is to be reported as a new serious 
adverse event.
During the entire study, the cause of death of a participant in a study, whether or not the event is 
expected or associated with the study vaccine, is considered a serious adverse event.
12.3.3.
Pregnancy
All initial reports of pregnancy in female participants or partners of male participants must be 
reported to the sponsor by the study site personnel within 24 hours of their knowledge of the event 
using the appropriate pregnancy notification form. Abnormal pregnancy outcomes 
(eg, spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are 
considered serious adverse events and must be reported using the serious adverse event form. Any 
participant who becomes pregnant during the study must be promptly withdrawn from further 
study vaccination but should continue participation in the study for follow-up of safety and 
immunogenicity if this does not result in a safety risk for the participant.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required.
12.4.
Contacting Sponsor Regarding Safety
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding safety issues or questions regarding the study are listed in the Contact Information 
page(s), which will be provided as a separate document.
13.
PRODUCT QUALITY COMPLAINT HANDLING
A product quality complaint (PQC) is defined as any suspicion of a product defect related to 
manufacturing, labeling, or packaging, ie, any dissatisfaction relative to the identity, quality, 
durability, or reliability of a product, including its labeling or package integrity. A PQC may have 
an impact on the safety and efficacy of the product. Timely, accurate, and complete reporting and 
analysis of PQC information from studies are crucial for the protection of participants, 
investigators, and the sponsor, and are mandated by regulatory agencies worldwide. The sponsor 
has established procedures in conformity with regulatory requirements worldwide to ensure 
appropriate reporting of PQC information; all studies conducted by the sponsor or its affiliates will 
be conducted in accordance with those procedures.

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13.1.
Procedures
All initial PQCs must be reported to the sponsor by the study site personnel within 24 hours after 
being made aware of the event.
If the defect is combined with a serious adverse event, the study site personnel must report the 
PQC to the sponsor according to the serious adverse event reporting timelines (refer to 
Section 12.3.2). A sample of the suspected product should be maintained for further investigation 
if requested by the sponsor.
13.2.
Contacting Sponsor Regarding Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding product quality issues are listed in the Contact Information page(s), which will be 
provided as a separate document.
14.
STUDY VACCINE INFORMATION
14.1.
Physical Description of Study Vaccines
14.1.1.
Ad26.ZEBOV
Ad26.ZEBOV is a monovalent, replication-incompetent Ad26-based vector that expresses the 
full-length EBOV Mayinga GP and is produced in the human cell line PER.C6®.
The Ad26.ZEBOV vaccine will be supplied at a nominal concentration of 1x1011 vp/mL in 1-mL 
single-use glass vials as a frozen liquid suspension to be thawed before use. Each vial contains an 
extractable volume of 0.5 mL. Refer to the IB for a list of excipients.3
The Ad26.ZEBOV vaccine is manufactured by IDT Biologika GmbH for Janssen Vaccines & 
Prevention B.V., The Netherlands.
14.1.2.
MVA-BN-Filo
MVA-BN-Filo is a recombinant multivalent vaccine intended for active immunization against 
Ebola and Marburg virus infection. MVA-BN-Filo is strongly attenuated; the vaccine is 
propagated in primary chicken embryo fibroblast cells and does not replicate in human cells. 
The MVA-BN-Filo vaccine is supplied at a nominal concentration of 2x108 Inf U/mL in 1-mL 
single-use glass vials as a frozen liquid suspension to be thawed before use. Each vial contains an 
extractable volume of 0.5 mL. Refer to the IB for a list of excipients.4
The MVA-BN-Filo vaccine is manufactured by IDT Biologika GmbH for Janssen Vaccines & 
Prevention B.V., The Netherlands.
14.2.
Packaging
All study vaccines will be manufactured and packaged in accordance with Good Manufacturing 
Practice (GMP). All study vaccines will be packaged and labeled under the responsibility of the 
sponsor. No study vaccine can be repacked or relabeled without prior approval from the sponsor.

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Further details for study vaccine packaging and labeling can be found in the Site Investigational 
Product Procedures Manual.
14.3.
Labeling
Study vaccines labels will contain information to meet the applicable regulatory requirements.
14.4.
Preparation, Handling, and Storage 
All study vaccine must be stored at controlled temperatures. Guidance on storage temperature is 
provided in the Site Investigational Product Procedures Manual.
Vials must be stored in a secured location with no access for unauthorized personnel. All study 
product storage equipment (including refrigerators, freezers) must be equipped with a continuous 
temperature monitor and alarm, and with back-up power systems. In the event that study vaccine
is exposed to temperatures outside the specified temperature ranges, all relevant data will be sent 
to the sponsor to determine if the affected study vaccine can be used or will be replaced. The 
affected study vaccine must be quarantined and not used until further instruction from the sponsor 
is received.
A pharmacist/qualified staff member will prepare all doses for vaccine administration and provide 
it for dispensing. Blinding will be achieved by preparation of study vaccine by unblinded qualified 
study site personnel not involved in any other study-related procedures, and by the administration 
of study vaccine in a masked syringe by a blinded study vaccine administrator.
Full details on the preparation, the holding time and storage conditions from the time of preparation 
to delivery of Ad26.ZEBOV and MVA-BN-Filo and active control are provided in the Site 
Investigational Product Procedures Manual and Site Blinding Plan.
14.5.
Study Vaccine Accountability
The investigator is responsible for ensuring that all study vaccine received at the study site is 
inventoried and accounted for throughout the study. The study vaccine administered to the 
participant must be documented on the Intervention Accountability Form. All study vaccine will 
be stored and disposed of according to the sponsor's instructions. Study site personnel must not 
combine contents of the study vaccine containers.
Study vaccine must be handled in strict accordance with the protocol and the container label, and 
must be stored at the study site in a limited-access area or in a locked cabinet under appropriate
environmental conditions. Unused study vaccine must be available for verification by the
independent study vaccine monitor during on-site monitoring visits. The return to the sponsor of 
unused study vaccine will be documented on the investigational product destruction form. When 
the study site is an authorized destruction unit and study vaccine supplies are destroyed on-site, 
this must also be documented on the Intervention Return Form.
Potentially hazardous materials such as used ampules, needles, syringes and vials containing 
hazardous liquids, should be disposed of immediately in a safe manner and therefore will not be 
retained for study vaccine accountability purposes. 

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Study vaccine should be dispensed under the supervision of the investigator or a qualified member 
of the study site personnel, or by a hospital/clinic pharmacist. Study vaccine will be supplied only 
to participants participating in the study. Returned study vaccine must not be dispensed again, even 
to the same participant. Study vaccine may not be relabeled or reassigned for use by other 
participants. The investigator agrees neither to dispense the study vaccine from, nor store it at, any 
site other than the study sites agreed upon with the sponsor.
15.
STUDY-SPECIFIC MATERIALS
The investigator will be provided with the following supplies:

Study protocol and IB and Addendum for Ad26.ZEBOV and MVA- BN-Filo

Site Investigational Product Procedures Manual, Site Blinding Plan

Syringes, needles, and study vaccines

Laboratory manual, laboratory kits, requisition forms, and shipment boxes

IWRS Manual 

Electronic Data Capture (eDC) Manual/eCRF Completion Guidelines

Sample ICF

Participant diaries

Rulers, thermometers

Participant wallet card 
16.
ETHICAL ASPECTS
16.1.
Study-specific Design Considerations
Potential participants will be fully informed of the risks and requirements of the study and, during 
the study, participants 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 participants who are fully able to understand the risks, 
benefits, and potential adverse events of the study, and provide their consent voluntarily will be 
enrolled.
The primary ethical concern is the safety of the enrolled participants.
The total blood volume to be collected is considered to be well below the limits of standard blood 
donation.

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16.2.
Regulatory Ethics Compliance
16.2.1.
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the 
protocol, current ICH guidelines on 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 participants. 
Compliance with this standard provides public assurance that the rights, safety, and well-being of 
participants are protected, consistent with the principles that originated in the Declaration of 
Helsinki, and that the study data are credible.
16.2.2.
Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or sponsor where required) will provide the IEC/IRB 
with current and complete copies of the following documents (as required by local regulations):

Final protocol and, if applicable, amendments

Sponsor-approved ICF (and any other written materials to be provided to the participants)

IB (or equivalent information) and amendments/addenda

Sponsor-approved participant recruiting materials

Information on compensation for study-related injuries or payment to participants 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 participants

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 
participants, data or study conduct, unless required locally), the ICF, applicable recruiting 
materials, and participant 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 participants, data or study conduct)

Revision(s) to ICF and any other written materials to be provided to participants

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
If applicable, new or revised participant recruiting materials approved by the sponsor

Revisions to compensation for study-related injuries or payment to participants for 
participation in the study, if applicable

New edition(s) of the IB 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 participants or the conduct of the 
study

Deviations from or changes to the protocol to eliminate immediate hazards to the participants

Report of deaths of participants under the investigator's care

Notification if a new investigator is responsible for the study at the study 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 participants, 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
Each participant must give written consent according to local requirements after the nature of the 
study has been fully explained. The ICF(s) must be signed before performance of any study-related 
activity. The ICF(s) that is/are used must be approved by both the sponsor and by the reviewing 
IEC/IRB and be in a language that the participant 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 participants the aims, methods, reasonably anticipated benefits, and 
potential hazards of the study, and any discomfort participation in the study may entail. Participants 
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 
they will receive. Finally, they will be told that the investigator will maintain a participant
identification register for the purposes of long-term follow up if needed and that their records may 
be accessed by health authorities and authorized sponsor personnel without violating the 

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confidentiality of the participant, to the extent permitted by the applicable law(s) or regulations. By 
signing the ICF the participant is authorizing such access. It also denotes that the participant agrees 
to allow his or her study physician to recontact the participant for the purpose of obtaining consent 
for additional safety evaluations, if needed.
The participant will be given sufficient time to read the ICF and the opportunity to ask questions. 
After this explanation and before entry into the study, consent should be appropriately recorded by 
means of the participant's personally dated signature. After having obtained the consent, a copy of 
the ICF must be given to the participant.
If the participant 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 participant or legally acceptable 
representative is obtained.
16.2.4.
Privacy of Personal Data
The collection and processing of personal data from participants 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 
participants confidential.
The informed consent obtained from the participant includes explicit consent for the processing of 
personal data and for the investigator/institution to allow direct access to his or her original medical 
records (source data/documents) for study-related monitoring, audit, IEC/IRB review, and regulatory 
inspection. This consent also addresses the transfer of the data to other entities and to other countries.
The participant has the right to request through the investigator access to his or her personal data and 
the right to request rectification of any data that are not correct or complete. Reasonable steps will 
be taken to respond to such a request, taking into consideration the nature of the request, the 
conditions of the study, and the applicable laws and regulations.
Exploratory research is not conducted under standards appropriate for the return of data to 
participants. In addition, the sponsor cannot make decisions as to the significance of any findings 
resulting from exploratory research. Therefore, exploratory research data will not be returned to 
participants or investigators, unless required by law or local regulations. Privacy and confidentiality 
of data generated in the future on stored samples will be protected by the same standards applicable 
to all other clinical data.

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16.2.5.
Long-term Retention of Samples for Additional Future Research 
Samples collected in this study may be stored for up to 15 years (or according to local regulations) 
for additional research. Samples will only be used to understand Ad26.ZEBOV, MVA-BN-Filo, to 
understand EVD, to understand differential vaccine responders, and to develop tests/assays related 
to Ad26.ZEBOV, MVA-BN-Filo, and EVD. The research may begin at any time during the study 
or the post-study storage period. 
Each participant will be asked to consent voluntarily for their blood samples to be stored for other 
research studies that may be done after this study is completed. Participants unwilling to have their 
blood samples stored for future use, can participate in the immunogenicity assessments without 
having their blood samples stored for future testing. In such case, their blood samples will be 
destroyed after all the immunogenicity tests have been concluded (as agreed by the sponsor).
All samples, for which consent has been obtained and for which additional material is available 
after study-specified testing is complete, will be stored for future testing. A PCR test may be 
performed to test for presence of EBOV in the samples if samples need to be exported. Applicable 
approvals will be sought before any such samples are used for analysis not specified in the protocol 
or a protocol amendment approved by the IEC/IRB. 
Stored samples will be coded throughout the sample storage and analysis process and will not be 
labeled with personal identifiers. Participants may withdraw their consent for their samples to be 
stored for research.
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 participants, 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 IEC/IRB (where 
required) only needs to be notified.
During the course of the study, in situations where a departure from the protocol is unavoidable, 
the investigator or other physician in attendance will contact the appropriate sponsor representative 
listed in the Contact Information page(s), which will be provided as a separate document. Except 
in emergency situations, this contact should be made before implementing any departure from the 
protocol. In all cases, contact with the sponsor must be made as soon as possible to discuss the 
situation and agree on an appropriate course of action. The data recorded in the eCRF and source 
documents will reflect any departure from the protocol, and the source documents will describe 
this departure and the circumstances requiring it.

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17.2.
Regulatory Documentation
17.2.1.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities 
in each respective country, if applicable. A study may not be initiated until all local regulatory 
requirements are met.
17.2.2.
Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study vaccine to the 
study site:

Protocol and amendment(s), if any, signed and dated by the 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, participant compensation programs. This approval must clearly identify the 
specific protocol by title and number and must be signed (or sealed, where appropriate per 
local regulations) by the chairman or authorized designee.

Name and address of the IEC/IRB, including a current list of the IEC/IRB members and their 
function, with a statement that it is organized and operates according to GCP and the 
applicable laws and regulations. If accompanied by a letter of explanation, or equivalent, from 
the IEC/IRB, a general statement may be substituted for this list. If an investigator or a 
member of the study site personnel is a member of the IEC/IRB, documentation must be 
obtained to state that this person did not participate in the deliberations or in the vote/opinion 
of the study.

Regulatory authority approval or notification, if applicable

Signed and dated statement of investigator (eg, Form FDA 1572), if applicable

Documentation of investigator qualifications (eg, curriculum vitae)

Completed investigator financial disclosure form from the principal investigator, where 
required

Signed and dated clinical trial agreement, which includes the financial agreement

Any other documentation required by local regulations
The following documents must be provided to the sponsor before enrollment of the first 
participant:

Completed investigator financial disclosure forms from all subinvestigators

Documentation of subinvestigator qualifications (eg, curriculum vitae)
17.3.
Participant Identification, Enrollment, and Screening Logs
The investigator agrees to complete a participant identification and enrollment log to permit easy 
identification of each participant during and after the study. This document will be reviewed by 
the sponsor study-site contact for completeness.

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The participant identification and enrollment log will be treated as confidential and will be filed 
by the investigator in the study file. To ensure participant confidentiality, no copy will be made. 
All reports and communications relating to the study will identify participants by participant
identification and age at initial informed consent. In cases where the participant is not randomized 
into the study, the date seen and age at initial informed consent will be used.
The investigator must also complete a participant screening log, which reports on all participants 
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: 
participant identification, eligibility, and study identification; study discussion and date of signed 
informed consent; dates of visits; results of safety and efficacy parameters as required by the 
protocol; record of all adverse events and follow-up of adverse events; concomitant medication; 
study vaccine receipt/dispensing/return records; study vaccine administration information; and 
date of study completion and reason for early discontinuation of study vaccine or withdrawal from 
the study, if applicable. 
The author of an entry in the source documents should be identifiable.
Specific details required as source data for the study and source data collection methods will be 
reviewed with the investigator before the study and will be described in the monitoring guidelines 
(or other equivalent document).
The following data will be recorded directly into the eCRF and will be considered source data:

Race

HIV status, as reported by the participant

Blood pressure and pulse/heart rate 

Height and weight

Details of physical examination
The participant diary will be considered a source document. Information from the diary provided 
to participants to record symptoms of solicited local and systemic adverse events until 7 days post
Dose 1, post Dose 2, and post booster dose (Groups 5-6 only) vaccinations, will be reviewed by 
the investigator or clinical designee to transcribe into the relevant parts of the eCRF as described 
in the CRF Completion Guidelines.
Inclusion and exclusion criteria not requiring documented medical history must be verified at a 
minimum by participant interview or other protocol required assessment (eg, physical 
examination) and documented in the source documents.

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An electronic source system may be utilized, which contains data traditionally maintained in a 
hospital or clinic record to document medical care (eg, electronic source documents) as well as the 
clinical study-specific data fields as determined by the protocol. This data is electronically 
extracted for use by the sponsor. If the electronic source system is utilized, references made to the 
eCRF in the protocol include the electronic source system but information collected through the 
electronic source system may not be limited to that found in the eCRF. Data in this system may be 
considered source documentation.
17.5.
Case Report Form Completion
Case report forms are prepared and provided by the sponsor for each participant in electronic 
format. All eCRF 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 eCRF 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.
Worksheets may be used for the capture of some data to facilitate completion of the eCRF. Any 
such worksheets will become part of the participant's source documents. Data must be entered into 
eCRF in English. The eCRF must be completed as soon as possible after a participant visit and the 
forms should be available for review at the next scheduled monitoring visit.
All subjective measurements (eg, pain scale information or other questionnaires) will be completed 
by the same individual who made the initial baseline determinations whenever possible.
If necessary, queries will be generated in the eDC tool. If corrections to a eCRF are needed after 
the initial entry into the eCRF, this can be done in either of the following ways:

Investigator and study site personnel can make corrections in the eDC tool at their own 
initiative or as a response to an auto query (generated by the eDC tool).

Sponsor or sponsor delegate can generate a query for resolution by the investigator and study
site personnel.
17.6.
Data Quality Assurance/Quality Control
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified 
investigators and appropriate study sites, review of protocol procedures with the investigator and 
study site personnel before the study, and periodic monitoring visits by the sponsor. Written 
instructions will be provided for collection, handling, storage, and shipment of samples. 
Guidelines for eCRF completion will be provided and reviewed with study site personnel before 
the start of the study. The sponsor will review eCRF for accuracy and completeness during on-site 
monitoring visits and after transmission to the sponsor; any discrepancies will be resolved with the 
investigator or designee, as appropriate. After upload of the data into the study database they will 
be verified for accuracy and consistency with the data sources.

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17.7.
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all eCRF 
and all source documents that support the data collected from each participant, as well as all study 
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a Clinical 
Trial, and all study documents as specified by the applicable regulatory requirement(s). The
investigator/institution will take measures to prevent accidental or premature destruction of these 
documents.
Essential documents must be retained until at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing applications 
in an ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical 
development of the investigational product. These documents will be retained for a longer period 
if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the 
responsibility of the sponsor to inform the investigator/institution as to when these documents no 
longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who will accept 
the responsibility. The sponsor must be notified in writing of the name and address of the new 
custodian. Under no circumstance shall the investigator relocate or dispose of any study documents 
before having obtained written approval from the sponsor.
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any 
documentation relating to this study, the investigator/institution must permit access to such reports.
17.8.
Monitoring
The sponsor will perform on-site monitoring visits as frequently as necessary. The monitor will 
record dates of the visits in a study site visit log that will be kept at the study site. The first 
post-initiation visit will be made as soon as possible after enrollment has begun. At these visits, 
the monitor will compare the data entered into the eCRF with the source documents (vaccination 
unit and/or clinic records). The nature and location of all source documents will be identified to 
ensure that all sources of original data required to complete the eCRF 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.

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There will be independent monitoring of the pharmacy and preparation of study vaccine by an 
unblinded monitor (independent study vaccine monitor, see DEFINITIONS OF TERMS); regular 
monitors will be blinded.
In addition to on-site monitoring visits, remote contacts can occur. It is expected that during these 
remote contacts, study site personnel will be available to provide an update on the progress of the 
study at the study site.
Central monitoring will take place for data identified by the sponsor as requiring central review.
17.9.
Study Completion/Termination
17.9.1.
Study Completion/End of Study
The study is considered completed with the last visit for the last participant participating in the 
study. The final data from the study site will be sent to the sponsor (or designee) after completion 
of the final participant visit/phone call at that study site, in the time frame specified in the clinical 
trial agreement.
17.9.2.
Study Termination
The sponsor reserves the right to close the study site or terminate the study at any time for any 
reason at the sole discretion of the sponsor. Study sites will be closed upon study completion. A
study site is considered closed when all required documents and study supplies have been collected 
and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are not 
limited to:

Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or 
local health authorities, the sponsor's procedures, or GCP guidelines

Inadequate recruitment of participants by the investigator

Discontinuation of further study vaccine development
17.10. On-site Audits
Representatives of the sponsor's clinical quality assurance department may visit the study site at 
any time during or after completion of the study to conduct an audit of the study in compliance 
with regulatory guidelines and company policy. These audits will require access to all study 
records, including source documents, for inspection. Participant 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.

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Similar auditing procedures may also be conducted by agents of any regulatory body, either as part 
of a national GCP compliance program or to review the results of this study in support of a 
regulatory submission. The investigator should immediately notify the sponsor if he or she has
been contacted by a regulatory agency concerning an upcoming inspection.
17.11. Use of Information and Publication
All information, including but not limited to information regarding Ad26.ZEBOV and 
MVA-BN-Filo or the sponsor's operations (eg, patent application, formulas, manufacturing 
processes, basic scientific data, prior clinical data, formulation information) supplied by the 
sponsor to the investigator and not previously published, and any data, including exploratory
research data, generated as a result of this study, are considered confidential and remain the sole 
property of the sponsor. The investigator agrees to maintain this information in confidence and use 
this information only to accomplish this study, and will not use it for other purposes without the 
sponsor's prior written consent.
The investigator understands that the information developed in the study will be used by the 
sponsor in connection with the continued development of Ad26.ZEBOV and MVA-BN-Filo, and 
thus may be disclosed as required to other clinical investigators or regulatory agencies. To permit 
the information derived from the clinical studies to be used, the investigator is obligated to provide 
the sponsor with all data obtained in the study.
The results of the study will be reported in a Clinical Study Report generated by the sponsor and 
will contain data from all study sites that participated in the study as per protocol. Recruitment 
performance or specific expertise related to the nature and the key assessment parameters of the 
study will be used to determine a coordinating investigator for the study. Results of exploratory
analyses performed after the Clinical Study Report has been issued will be reported in a separate 
report and will not require a revision of the Clinical Study Report. Study participant 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 

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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 18 months after study end date, 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 International Committee 
of Medical Journal Editors (ICMJE) Recommendations for the Conduct, Reporting, Editing and 
Publication of Scholarly Work in Medical Journals, which state that the named authors must have 
made a significant contribution to the conception or design of the work; or the acquisition, analysis, 
or interpretation of the data for the work; and drafted the work or revised it critically for important 
intellectual content; and given final approval of the version to be published; and agreed to be 
accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity 
of any part of the work are appropriately investigated and resolved.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and disclose the existence of and the results of clinical studies as required 
by law.

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REFERENCES
1.
Baize S, Pannetier D, Oestereich L, et al. Emergence of Zaire Ebola virus disease in Guinea. N Engl J Med. 
2014;371(15):1418-1425.
2.
Friedrich B, Trefry J, Biggins J, et al. Potential vaccines and post-exposure treatments for filovirus infections. 
Viruses. 2012;4(9):1619-1650.
3.
Investigator’s Brochure: JNJ-61210474 (Ad26.ZEBOV) Edition 6. Janssen Vaccines & Prevention B.V. 
(January 2019). For updated information, refer to Edition 6 Addendum 1 (Janssen Vaccines & Prevention, 
17 May 2019).
4.
Investigator’s Brochure: JNJ-63839880 (MVA-BN-Filo [MVA-mBN226B]) Edition 12. Janssen Vaccines & 
Prevention B.V. (December 2018). For updated information, refer to Edition 12 Addendum 1 (Janssen 
Vaccines & Prevention, 17 May 2019).
5.
Marcy SM, Kohl KS, Dagan R, et al./The Brighton Collaboration Fever Working Group. Fever as an adverse 
event following immunization: case definition and guidelines of data collection, analysis, and presentation. 
Vaccine. 2004:22;551-556.
6.
WHO Fact Sheet Ebola Virus Disease, Updated 30 May 2019. Available at: https://www.who.int/news-
room/fact-sheets/detail/ebola-virus-disease. Accessed July 2019WHO.