A Phase 2 Randomized, Multi-Center Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Immunogenicity of the V920 (rVSVΔG-ZEBOV-GP) Ebola Virus Vaccine Candidate in HIV-Infected Adults and Adolescents
Phase: PHASE2
Conditions: Ebola
Sponsor: Canadian Immunization Research Network

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CT14B_ACHIV-Ebola Protocol Version 4.0 
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NCT03031912 
 
A Phase 2 Randomized, Multi-Center Double-Blind, Placebo-Controlled Study to Evaluate 
the Safety and Immunogenicity of 1 or 2 doses of the V920 (rVSVΔG-ZEBOV-GP) Ebola 
Virus Vaccine Candidate in HIV-Infected Adults and Adolescents 
 
Short Title:  African-Canadian Study of HIV-Infected Adults and a Vaccine for Ebola – 
ACHIV-Ebola (Merck Study V920-015) 
 
SPONSOR: 
Dalhousie University 
(Institution representing Canadian Immunization Research Network –CIRN) 
MANUFACTURER: 
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. 
 
 
Canadian Immunization Research Network (CIRN) NOMINATED PRINCIPAL 
INVESTIGATOR: 
Scott A. Halperin, MD 
 
Canadian Immunization Research Network (CIRN) COORDINATING PRINCIPAL 
INVESTIGATOR: 
Joanne M. Langley, MD 
 
PRINCIPAL INVESTIGATOR: 
Cécile Tremblay, MD 
 
CO-INVESTIGATORS (SITE): 
Curtis Cooper, MD 
Innocent Valea, PhD 
Souleymane Mboup, MD 
Cécile Tremblay, MD 
 
COLLABORATING INVESTIGATORS: 
Nicolas Chomont, MD 
 
 
 
Protocol-specific Sponsor, Manufacturer and Investigator Contact information can be found in the 
Investigator Trial File Binder (or equivalent). 
 

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TABLE OF CONTENTS 
1.0 TRIAL SUMMARY ..................................................................................................... 25 
2.0 TRIAL DESIGN ........................................................................................................... 26 
2.1 
Trial Design............................................................................................................... 26 
2.2 
Trial Diagram ........................................................................................................... 28 
3.0 OBJECTIVE(S) & HYPOTHESIS (ES) .................................................................... 29 
3.1 
Primary Objective(s) & Hypothesis (es) ................................................................ 29 
3.2 
Secondary Objective(s) ............................................................................................ 29 
3.3 
Tertiary Objective(s)................................................................................................ 29 
4.0 BACKGROUND & RATIONALE ............................................................................. 30 
4.1 
Background............................................................................................................... 30 
4.1.1 
Pharmaceutical and therapeutic background ......................................................... 34 
4.1.2 
Pre-clinical Trials .................................................................................................. 35 
4.1.3 
Ongoing Clinical Trials ......................................................................................... 35 
4.2 
Rationale ................................................................................................................... 36 
4.2.1 
Rationale for the Trial and Selected Subject Population ....................................... 36 
4.2.2 
Rationale for Dose Selection/Regimen/Modification............................................ 36 
4.2.2.1 Rationale for the Use of Placebo Control ..................................................... 36 
4.2.2.2 Vaccine Dose for This Trial ......................................................................... 37 
4.2.3 
Rationale for Endpoints ......................................................................................... 37 
4.2.3.1 Immunogenicity Endpoints........................................................................... 37 
4.2.3.2 Safety Endpoints ........................................................................................... 38 
4.3 
Benefit/Risk............................................................................................................... 38 
4.3.1 
Risks ...................................................................................................................... 39 
4.3.1.1 Local Reactions ............................................................................................ 39 
4.3.1.2 Systemic Reactions ....................................................................................... 39 
4.3.1.3 Reactions to V920 ........................................................................................ 39 
4.3.1.4 Pregnancy...................................................................................................... 40 
4.3.1.5 Lactation ....................................................................................................... 40 
4.3.1.6 Venipuncture ................................................................................................. 40 

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4.3.1.7 Allergic Reaction .......................................................................................... 40 
4.3.1.8 Unknown Risks ............................................................................................. 41 
4.3.1.9 Risks to the Study Personnel and the Environment ...................................... 41 
4.3.2 Intended Benefit for Subjects....................................................................................... 42 
5.0 METHODOLOGY ....................................................................................................... 42 
5.1 
Entry Criteria ........................................................................................................... 42 
5.1.1 
Diagnosis/Condition for Entry into the Trial ......................................................... 42 
5.1.2 
Subject Inclusion Criteria ...................................................................................... 42 
5.1.3 
Subject Exclusion Criteria ..................................................................................... 43 
5.2 
Trial Vaccination...................................................................................................... 44 
5.2.1 
Formulation, Packaging, and Labeling of V920.................................................... 45 
5.2.2 
Storage and Stability .............................................................................................. 45 
5.2.3 
Preparation, Administration, and Dosage of V920................................................ 45 
5.2.4 
Dose Selection/Modification ................................................................................. 46 
5.2.4.1 Dose Selection (Preparation) ........................................................................ 46 
5.2.5 
Timing of Dose Administration ............................................................................. 46 
5.2.6 
Trial Blinding ........................................................................................................ 46 
5.3 
Randomization or Treatment Allocation or Vaccine Allocation ......................... 46 
5.4 
Stratification ............................................................................................................. 46 
5.5 
Concomitant Medications/Vaccinations (Allowed & Prohibited) ....................... 47 
5.6 
Rescue Medications & Supportive Care ................................................................ 47 
5.7 
Subject Withdrawal/Discontinuation Criteria ...................................................... 47 
5.8 
Subject Replacement Strategy ................................................................................ 48 
5.9 
Beginning and End of the Trial............................................................................... 48 
5.10 
Clinical Criteria for Early Trial Termination ....................................................... 48 
6.0 TRIAL FLOW CHART ............................................................................................... 49 
7.0 TRIAL PROCEDURES ............................................................................................... 52 
7.1 
Trial Procedures ....................................................................................................... 56 
7.1.1 
Administrative Procedures .................................................................................... 56 
7.1.1.1 Informed Consent ......................................................................................... 56 

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7.1.1.1.1 General Informed Consent .................................................................... 56 
7.1.1.2 Inclusion/Exclusion Criteria ......................................................................... 57 
7.1.1.3 Subject Identification Card ........................................................................... 57 
7.1.1.4 Medical History ............................................................................................ 57 
7.1.1.5 Prior and Concomitant Medications Review ................................................ 57 
7.1.1.5.1 Prior Medications .................................................................................. 57 
7.1.1.5.2 Concomitant Medications...................................................................... 57 
7.1.1.6 Assignment of Screening Number ................................................................ 57 
7.1.1.7 Assignment of Treatment/Randomization Number ...................................... 58 
7.1.1.8 Trial Compliance .......................................................................................... 58 
7.1.2 
Clinical Procedures/Assessments .......................................................................... 58 
7.1.3 
Laboratory Procedures/Assessments ..................................................................... 59 
7.1.3.1 Laboratory Evaluations (Hematology, Chemistry and Urinalysis) .............. 59 
7.1.4 
Other Procedures ................................................................................................... 60 
7.1.4.1 HIV Viral Load ............................................................................................. 60 
7.1.4.2 Withdrawal/Discontinuation ......................................................................... 60 
7.1.4.3 Blinding/Unblinding ..................................................................................... 60 
7.1.4.4 Calibration of Critical Equipment ................................................................ 61 
7.1.5 
Visit Requirements ................................................................................................ 61 
7.1.5.1 Screening ...................................................................................................... 61 
7.1.5.2 Vaccination Visit .......................................................................................... 61 
7.2 
Assessing and Recording Adverse Events .............................................................. 61 
7.2.1 
Definition of an Overdose and Reporting Overdose to the Sponsor ..................... 62 
7.2.2 
Events Specific to Post Vaccination ...................................................................... 62 
7.2.3 
Reporting of Pregnancy and Lactation to the Sponsor .......................................... 62 
7.2.4 
Immediate Reporting of Adverse Events to the Sponsor ...................................... 63 
7.2.4.1 Serious Adverse Events ................................................................................ 63 
7.2.4.2 Events of Clinical Interest ............................................................................ 64 
7.2.5 
Evaluating Adverse Events .................................................................................... 64 
7.2.6 
Sponsor Responsibility for Reporting Adverse Events ......................................... 67 
7.3 
TRIAL GOVERNANCE AND OVERSIGHT ...................................................... 67 

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7.3.1 
Stakeholder Group ................................................................................................. 67 
7.3.2 
Trial Steering Committee ...................................................................................... 67 
7.3.3 
Data Safety and Monitoring Board ........................................................................ 67 
8.0 STATISTICAL ANALYSIS PLAN ............................................................................ 68 
8.1 
Statistical Analysis Plan Summary ......................................................................... 68 
8.2 
Statistical Analysis Plan Detailed Description....................................................... 70 
8.2.1 
Responsibility for Analyses/In-House Blinding .................................................... 70 
8.2.2 
Objectives/Hypotheses .......................................................................................... 70 
8.2.3 
Analysis Endpoints ................................................................................................ 70 
8.2.3.1 Immunogenicity Endpoints........................................................................... 70 
8.2.4 
Analysis Populations ............................................................................................. 70 
8.2.4.1 Immunogenicity Analysis Populations ......................................................... 70 
8.2.4.2 Safety Analysis Populations ......................................................................... 71 
8.2.5 
Statistical Methods ................................................................................................ 71 
8.2.5.1 Statistical Methods for Immunogenicity Analyses ....................................... 71 
8.2.5.2 Statistical Methods for Safety Analyses ....................................................... 72 
8.2.5.3 Summaries of Baseline Characteristics, Demographics, and Other Analyses72 
8.2.6 
Multiplicity ............................................................................................................ 72 
8.2.7 
Sample Size and Power Calculations .................................................................... 72 
8.2.8 
Subgroup Analyses and Effect of Baseline Factors............................................... 73 
8.2.9 
Interim Analysis .................................................................................................... 73 
9.0 LABELING, PACKAGING, STORAGE AND RETURN OF CLINICAL SUPPLIES
 
73 
9.1 
Investigational Product............................................................................................ 73 
9.2 
Packaging and Labeling Information..................................................................... 74 
9.3 
Clinical Supplies Disclosure .................................................................................... 74 
9.4 
Storage and Handling Requirements ..................................................................... 75 
9.5 
Discard/Destruction/Returns and Reconciliation.................................................. 75 
9.6 
Standard Policies ...................................................................................................... 75 
10.0 LIST OF REFERENCES ............................................................................................. 76 

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11.0 Appendix 1: List of Abbreviations: ............................................................................. 78 
12.0 APPENDIX 2: Laboratory Abnormalities ................................................................. 80 
13.0 APPENDIX 3: Stopping Rules .................................................................................... 83 
 

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LIST OF TABLES 
 
Table 1: Ebolavirus Outbreaks.......................................................................................................... 30 
Table 2: Trial Treatment/Vaccination .............................................................................................. 44 
Table 3: Laboratory Tests ................................................................................................................. 59 
Table 4: Evaluating Adverse Events ................................................................................................ 65 
Table 5: Product Descriptions .......................................................................................................... 74 
 

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LIST OF FIGURES 
 
 
Figure 1: Trial Diagram .................................................................................................................... 28 
Figure 2: Total suspected, probable, and confirmed cases of Ebola virus disease in Guinea, 
Liberia, and Sierra Leone. .................................................................................................... 32 
Figure 3: (A) A single-stranded, negative-sense RNA encoding 5 transcriptional units: N 
(nucleoprotein), P (phosphoprotein), M (matrix), G (glycoprotein), and L (polymerase). .. 34 
 
 
 

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AMENDMENT HISTORY 
Amendment 
No. 
Protocol 
Version 
No. 
Date issued 
Author(s) of 
changes 
Details of Changes made 
1 
2.2 
02Aug2016 
Dr. Joanne 
Langley 
Cover page of protocol: Short Title: 
African-Canadian Study of HIV-
Infected Adults and a Vaccine for Ebola 
– (ACHIV-Ebola) has been added. 
1 
2.2 
02Aug2016 
Dr. Joanne 
Langley 
Headers and footers changed to reflect 
new protocol version number and  date. 
1 
2.2 
02Aug2016 
Dr. Joanne 
Langley 
 Section 4.2.3.2  Safety Endpoints.  
Changes have been made to reflect the 
collection of some solicited AE’s until 
14 days, and some for the full 42 day 
post vaccination period.   
1. a. i. The occurrence of each solicited 
local and systemic AE, during a 14-day 
follow-up period following vaccination, 
and  fever, arthritis, arthralgia, rash and 
blisters/vesicular lesions during a 42-
day follow –up period following 
vaccination. 
Clarification to what constitutes D0-
D42 is added in the first paragraph. 
“The Memory Aid will prompt the 
subject to record his/her temperature for 
42 days following vaccination starting 
with the day of vaccination (D0-D42).  
Injection site and systemic reactions 
will be monitored for 14-days post-
vaccination (D0-D14). 
 
In addition subjects will be prompted 
for joint pain, joint swelling,  rashes, 
and blisters or vesicular lesions during 
the 42-day post-vaccination period as 
these events have been reported in the 
development program.” 

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Table 4: Evaluating Adverse Events-
Maximum Intensity-Day 5 changed to 
Day 14.  “ Injection site redness or 
swelling from the day of vaccination 
through Day 14 post-vaccination will be 
evaluated by maximum size. 
1 
2.2 
02Aug2016 
Dr. Joanne 
Langley 
5.1.2.  Subject Inclusion Criteria.  
Inclusion Criteria #8 has been changed 
from “14 days” to “6 weeks”. 
2 
2.3 
26Aug2016 
Dr. Joanne 
Langley 
Various grammatical and formatting 
edits.  Headers and footers changed to 
reflect new protocol version number 
and date. 
2 
2.3 
26Aug2016 
Dr. Joanne 
Langley 
Section 5.2.3 Preparation, 
Administration, and Dosage of V920 
and Section 9.3, Clinical Supplies 
Disclosure-clarification throughout that 
administration of vaccine/placebo may 
be done by blinded or unblinded 
personnel.    
2 
2.3 
26Aug2016 
Dr. Joanne 
Langley 
Section 5.9 Beginning and End of the 
Trial-The original wording has been 
replaced with the following, for greater 
detail.  “The overall trial begins when the 
first subject signs the informed consent 
form. The subject participation portion 
of the overall trial ends when the last 
subject completes the last study-related 
phone call or visit, discontinues from the 
trial or is lost to follow-up (i.e., the 
subject is unable to be contacted by the 
investigator). For purposes of analysis 
and reporting, the overall trial ends when 
the Sponsor receives the last serology 
assay result or subject data from the last 
study-related phone call or visit and the 
database has been cleaned and locked.” 
2 
2.3 
26Aug2016 
Dr. Joanne 
Langley 
Section 6. Trial Flow Chart.  Blood 
volumes have been added to the flow 
chart. 

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2 
2.3 
26Aug2016 
Dr. Joanne 
Langley 
Section7.1.4.3. Blinding/ Unblinding.  
Paragraph explaining emergency 
unblinding added. 
3 
2.4 
18Nov2016 
Dr. Joanne 
Langley 
Headers and footers changed to reflect 
new protocol version number and date. 
Table of Contents updated 
3 
2.4 
18Nov2016 
Dr. Joanne 
Langley 
Section 2.1 Trial Design (P11).    
Dakar site name has been updated to 
Institut de Recherche en Santé,de 
Surveillance Epidemiologique et de 
Formations  
3 
2.4 
18Nov2016 
Dr. Joanne 
Langley 
Section 5.1.2 Subject Inclusion 
Criteria.  Inclusion criteria 7 and 8a 
have been modified by removing the 
word ‘female’ from the statement 
Inclusion criteria 7a”if the female 
partner” and then removing inclusion 
criteria 8a.  so the criteria are inclusive 
of contraception for all sexual 
persuasions and inclusive of timelines 
for both contraception and viral 
shedding. 
3 
2.4 
18Nov2016 
Dr. Joanne 
Langley 
Section 5.2.3 Preparation, 
Administration, and Dosage of 
V920.(p29)  and Section 9.3 Clinical 
Supplies Disclosure (p 53) 
Clarification only BLINDED personnel 
will administer the study product, to 
protect the blind.  
Need length recommendation changed 
from 23G  1.5 inches to 23 G 1 inch, for 
harmonization throughout the protocol. 
3 
2.4 
18Nov2016 
Dr. Joanne 
Langley 
Section 7.1.1.4 Medical History (p36) 
Clarification on collection of medical 
history to include all pre-existing 
conditions or signs and/or symptoms 
present in the participant prior to the 
first study injection. 
3 
2.4 
18Nov2016 
Dr. Joanne 
Langley 
Section 7.1.3 Laboratory 
Procedures/Assessments  (p37) 
3mls/kg in an 8 week period has been 
replaced with the NIH recommendation 
of no more than 10.5mls/kg or 550mls, 

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whichever is less, in an eight week 
period. 
 
The following statement has been 
clarified regarding the option nature of 
these samples and reworded as: In 
addition to anti-Ebola immune 
assessments blood samples, optional  
blood samples will be drawn at visits 1, 
5, 7, & 8 if subjects sign a separate 
consent form.  These samples will be 
conserved in a biobank for future 
research studies.  
  
Names and locations of labs have been 
added. 
3 
2.4 
18Nov2016 
Dr. Joanne 
Langley 
Section 7.3.1.1 Laboratory 
Evaluations (Hematology, Chemistry 
and Urinalysis)  (p38) 
Clarifications to table for destination of 
study samples to different labs. 
3 
2.4 
18Nov2016 
Dr. Joanne 
Langley 
Section 7.2 Assessing and Recording 
Adverse Events (p40)  
Added for clarification:  Pre-existing 
conditions or signs and/or symptoms 
present in a participant prior to the first 
study injection are not considered to be 
adverse events.  These events will be 
recorded in the participants’ medical 
history. 
3 
2.4 
18Nov2016 
Dr. Joanne 
Langley 
Section 7.1.3.1 Laboratory Safety 
Evaluations (Hematology, Chemistry 
and Urinalysis) Hematocrit removed 
from the table as it will not be collected 
for analysis 
4 
2.5 
14Dec2016 
Dr. Joanne 
Langley 
Various grammatical and formatting 
edits.  Headers and footers changed to 
reflect new protocol version number 
and date. 
4 
2.5 
14Dec2016 
Dr. Joanne 
Langley 
Summary of changes added (p10) 

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4 
2.5 
14Dec2016 
Dr. Joanne 
Langley 
Axillary temperature added throughout 
as option for assessing for a fever, as 
this is the route used by the African 
sites. 
4 
2.5 
14Dec2016 
Dr. Joanne 
Langley 
Section 2.1 Trial Design (p11) 4th 
paragraph, second sentence, removed 
‘and immunogenicity’ form the 
monitoring done by the DSMB.  They 
are monitoring safety, not 
immunogenicity. 
4 
2.5 
14Dec2016 
Dr. Joanne 
Langley 
Section 7.2.2Events Specific to Post 
Vaccination.  This section added for 
guidance in assessment and work-up of 
arthralgia/arthritis, rashes and vesicular 
lesions.   
5 
2.6 
12Jan2017 
Dr. Joanne 
Langley 
Table numbers have been corrected. 
5 
2.6 
12Jan2017 
Dr. Joanne 
Langley 
Section 5.1.2 Subject Inclusion 
Criteria #8: ‘6 weeks after vaccination’ 
changed to ‘8 weeks after vaccination’ 
for harmonization within the protocol. 
5 
2.6 
12Jan2017 
Dr. Joanne 
Langley 
Section 5.1.3 Subject Exclusion 
Criteria #6:Correction of ‘…or any 
other cytotoxic or immunosuppressive 
drug within six months’  to ‘or any 
other cytotoxic or immunosuppressive 
drug within ….12 months’. 
5 
2.6 
12Jan2017 
Dr. Joanne 
Langley 
Section 5.1.3 Subject Exclusion 
Criteria #13: Range given for axillary 
temperature (37.80C) 
5 
2.6 
12Apr2017 
Dr. Joanne 
Langley 
Cover Page Nicholas Meda, MD 
removed and Innocent Valea, MD 
added to Co-Investigator list 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Replaced ‘Group/s with Cohort/s 
throughout the document for 
consistency 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 1.0 Trial Summary:  
Added Cohort 5 details:  50 adults and 
adolescents CD4 ≥ 200 cells/mm^3, 
increased total number of trial 
participants to 250; Changed the 

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duration of enrollment to 30 months; 
changed the duration of participation to 
include cohort 5. 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 2.0 Trial Design: Added cohort 
5 details: 50 adults and adolescents CD4 
≥ 200 cells/mm^3, increased total 
number of trial participants to 250; first 
dose of vaccine or placebo at D0 and 
second dose of matching vaccine or 
placebo at D56.  The fourth safety 
analysis will be conducted when the 
fourth cohort (adolescents CD4 ≥ 200 
cells/mm3) will have completed 42 days 
of follow-up post vaccination 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 2.1 Trial Design: Removed 
(160:40 and 40:10) as the ratio of 4:1 is 
mentioned 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 2.2 Trial Diagram: Added 
cohort 5  
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 3.0 Objectives(s) and 
Hypotheses  
Added cohort 5 primary objective (s)  
1. Added ‘combined’ at the end of 
objective.  
  
2.  The geometric mean titer (GMT) 
of GP-ELISA in V920 vaccinated 
HIV-infected adults and adolescents 
will be superior to the GMT of the 
GP-ELISA in placebo vaccinated 
HIV-infected adults and adolescents 
Day 28 after the last dose of vaccine 
(equivalent to Day 84 from first 
dose) in Cohort 5 
 
Added cohort 5 secondary objective (s)  

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4. Objective:  Evaluate the safety 
and tolerability of two doses of 
V920 in HIV-infected adults and 
adolescents administered 56 days 
apart. 
5. Objective: Evaluate the 
immunogenicity of two doses of 
V920 administered 56 days apart via 
ZEBOV-specific antibody responses 
induced by V920 at D28 post-dose 2 
in HIV-infected adults and 
adolescents. 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 4.1 Background 
Table 1: Ebolavirus Outbreaks 
Updated 
the 
above 
table 
with 
information on Ebolavirus outbreaks 
from 2014-2017 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 4.2.2.2 Vaccine Dose for This 
Trial:  
Added: ‘or placebo’ to the first sentence 
Added following to the statement in this 
section. ‘in all Cohorts 1-5.  In Cohort 5, 
at Day 56 a second dose of matching 
vaccine (≥2 x 107 pfu/ml) or placebo will 
be administered. 
Added the following:  The rationale for 
assessing a second dose in HIV positive 
subjects is to assess whether a second dose 
will provide a greater immune response or 
a response in a greater proportion of 
subjects in case one dose is less 
immunogenic in HIV positive subjects 
than in non-HIV positive subjects 
assessed in other studies.  The 56 day 
interval is based on the interval utilized in 

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other studies that include non-HIV 
positive adults and children. 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 4.2.3.1 Immunogenicity 
Endpoints 
Added the following to the Primary End 
points: 
a. Added ‘in Cohorts 1-5 
combined’. 
b. ZEBOV-specific antibody 
responses measured by ELISA 
and neutralization on Day 28 
after the last dose of vaccine 
(equivalent to Day 84 from first 
dose) in Cohort 5. 
Added the following to the Secondary 
endpoints: 
a.  ZEBOV-specific antibody 
responses measured by ELISA and 
neutralization on Day 28 in Cohort 
5. 
 b.  added ‘after the first dose of 
vaccine’ 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 4.2.3.2 Safety Endpoints: 
Added ‘each vaccination’ to primary 
endpoint ‘iii’ 
Added ‘following each vaccination, to 
secondary endpoint ‘a’ 
Replaced post-vaccination with first 
vaccination for clarity in reporting 
SAEs 

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6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 4.3.1.3 Reactions to V920 
Changed Phase I-III to 2-3 for 
consistency with title 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 4.3.1.4 
Added ‘the last’ to abstinence and 
contraception precautions 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 5.2 Trial Vaccination 
Updated Table 2 to reflect cohort 5 
receipt of 2 doses, under 
Randomization/Vaccination to add ‘and 
Visit 7 (Day 56), where applicable’ 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 5.2 Trial Vaccination 
Updated Table 2, under 
Randomization/Vaccination to add ‘and 
Visit 7 (Day 56), where applicable’  and 
‘Subjects in Cohort 5 will receive two 
doses of V920 ≥2x107 PFU or two 
doses of normal saline placebo (0.9%) 
on D0 and D56.’ 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 5.2.5 Timing of Dose 
Administration 
Added: Subjects in Cohort 5 will also 
receive on D56 a matching dose of 
either the V920 at a dose of ≥2x107 
PFU in 1mL IM, or normal saline 
(0.9%) placebo control in 1mL volume. 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 5.4 Stratification 
Updated as follows: 
To satisfy the requirement that each site 
enrolls at least one placebo subject in 
each cohort, enrollment will proceed 
until treatments have been randomized 

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to at least one complete block of 
subjects (consisting of four subjects 
receiving treatment and one receiving 
placebo) at each site. 
 
Treatment allocation/randomization will 
be stratified by the 5 cohort groups: 
        Cohort 1: Screening CD4 cell 
counts for adults: CD4 cells/mm3 ≥ 500 
        Cohort 2: Screening CD4 cell 
counts for adults: CD4 cells/mm3 >350 
and < 500 
        Cohort 3: Screening CD4 cell 
counts for adults: CD4 cells/mm3 ≥ 200 
and ≤ 350 
        Cohort 4: Screening CD4 cell 
counts for adolescents, age 13 to 17: 
CD4 cells/mm3 ≥ 200 
        Cohort 5: Screening CD4 cell 
counts for adults and adolescents, age 
13 to 17: CD4 cells/mm3 ≥ 200 with 2 
doses. 
 
All sites are stratified by site Cohort 5 is 
stratified by site, and by age group 
(adolescent vs. adult). Once three 
blocks of five adolescents have been 
enrolled, with at least one block at each 
site, the requirement to enroll at least 12 
adolescents in Cohort 5 will be met. 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 6.0 Trial Flow Chart 
Added: (COHORTS 1 TO 4) 
Added to footnote b: Specimens should 
be obtained for ZEBOV-specific Serum 
Antibodies and ZEBOV-specific Serum 
Antibodies before vaccination   
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 6.0 Trial Flow Chart 
Added: (Cohort 5) as a separate Flow 
Chart for cohort 5 

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CT14B_ACHIV-Ebola Protocol Version 4.0 
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6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 7.1.3 Laboratory 
Procedures/Assessments 
Added the following for optional 
laboratory blood collection: (cohorts 1-
4) and at visits 1, 5, 7, 11, 13 & 14 
(cohort 5). 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 7.2 Clinical 
Procedures/Assessments 
Separated the procedures for Cohorts 1-
4 and Cohort 5 for clarity. 
Added:  Cohort 5:  
At visit 1 (Randomization /vaccination), 
the inclusion and exclusion criteria will 
be reviewed by the investigator or 
qualified designee to ensure that the 
subject still qualifies for the trial. At 
visit 1 (first dose of vaccine or placebo) 
and visit 7 (second dose of matching 
vaccine or placebo), vital Signs will be 
taken (including heart rate, blood 
pressure, oral/tympanic/axillary 
temperature, respiratory rate) 
Participant will be coming to the center 
at day 3 (visit 2), day 7 (visit 3), day 14 
(visit 4), day 28 (visit 5), day 42 (visit 
6), day 56 (visit 7), 3 days post dose 2 
(visit 8), 7 days post dose 2 (visit 9), 14 
days post dose 2 (visit 10), 28 days post 
dose 2 (visit 11), 42 days post dose 2 
(visit 12), day180 (visit 13) and day 365 
(visit 14).  Vital Signs will be taken 
(including heart rate, blood pressure, 
oral/tympanic/axillary temperature, 
respiratory rate) at all visits.  Non-
Serious Adverse Events including 
solicited and unsolicited adverse events 
will be monitored at every visit after 
first dose of vaccine or placebo through 
Day 42.  Non-Serious Adverse Events 

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CT14B_ACHIV-Ebola Protocol Version 4.0 
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including solicited and unsolicited 
adverse events will be monitored at 
every visit after second dose of 
matching vaccine or placebo through 
Day 42. Serious Adverse Events will be 
monitored at every visit through Day 
365.  
 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 7.1.5.2 Vaccination Visit  
Added: to participants in Cohort 1-4.  
Two doses of study vaccine will be 
administered to Cohort 5 participants at 
first at visit 1 and second dose at visit 7 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
SECTION 7.2.4.1 SERIOUS 
ADVERSE EVENTS 
Added ‘first’ to this sentence for clarity: 
For the time period beginning at 
treatment allocation/randomization 
through 365 days following first 
vaccination 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 7.2.4.2 Events of Clinical 
Interest  
Corrected the time period for reporting 
ECI from 14 (for non-live virus 
vaccine) to 42 days (live virus vaccine) 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 8.1 Statistical Analysis Plan 
Summary 
Updated section to include Cohort 5 
analysis plan summary 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 8.2.2 Objective(s) and 
Hypotheses(s) 
Primary Hypotheses:   

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1) The geometric mean titer (GMT) of 
GP-ELISA in V920 vaccinated HIV-
infected adults and adolescents will 
be superior to the GMT of the GP-
ELISA in placebo vaccinated HIV-
infected adults at Day 28 in Cohorts 
1-5 combined.  
2) The geometric mean titer (GMT) of 
GP-ELISA in V920 vaccinated 
HIV-infected adults and adolescents 
will be superior to the GMT of the 
GP-ELISA in placebo vaccinated 
HIV-infected adults and adolescents 
Day 28 after the last dose of vaccine 
(equivalent to Day 84 from first 
dose) in Cohort 5 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 8.2.3.1 Immunogenicity 
Endpoints 
Added to include biobank blood draws in 
Cohort 5: 
Participants who consent to bio-bank 
will undergo up to six blood draws in 
cohort 5: at baseline on the day of 
vaccination before vaccine or placebo is 
administered; at D28 post-vaccination; 
at D56 on the day of second dose of 
vaccination before vaccine or matching 
placebo is administered, at 28 days post-
dose 2 vaccination, at D180 post dose 1-
vaccination; and at D365 post dose 1-
vaccination. 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 8.2.5.1 Statistical Methods for 
Immunogenicity Analyses 
Added:’and Geometric Mean Fold 
Increase from baseline (GMFI)’ 
Updated this section to describe how the 
immunogenicity and safety for the 

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CT14B_ACHIV-Ebola Protocol Version 4.0 
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second dose in Cohort 5 will be 
summarized 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 8.2.7 Sample Size and Power 
Calculations 
Updated with cohort 5 sample size and 
power calculations 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 8.2.9 Interim Analyses 
Changed to reflect ‘four safety analyses 
will be conducted, one for each of the 
first four cohorts 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 9.1 Investigational Product 
Changes made to reflect the dosing for 
cohort 5 
6 
2.7 
11May17 
Dr. Joanne 
Langley 
Section 9.1 Investigational Product 
Treatment Allocation: Changes made to 
reflect the dosing for cohort 5 
7 
2.8 
Not a valid 
version 
 
Draft document 
7 
2.9 
Not a valid 
version 
 
Draft document 
7 
3.0 
10 January 
2018 
Dr. Joanne 
Langley 
Section 5.1.2 Subject Inclusion 
Criteria #1 increase inclusion age to 
70.  
7 
2.1. 
10 January 
2018 
Dr. Joanne 
Langley 
Section 2.1. Clarified that participant 
allotment between the sites may be 
reassigned based on enrolment between 
sites in order to ensure the integrity of 
the study. 

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7 
3.0 
10 January 
2018 
Dr. Joanne 
Langley 
Section 5.1.3 Subject Exclusion 
Criteria #3 deleted. Will now include 
health care workers.  
7 
3.0 
10 Janaury 
2018 
Dr. Joanne 
Langley 
Section 4.1.2 Rationale for the Trial 
and Selected Subject Population: 
Added the rationale for inclusion of 
HIV positive subjects 66-70 years of 
age. 
7 
3.0 
10 January 
2018 
Dr. Joanne 
Langley 
Section 4.3.1.9 Risks to the Study 
Personnel and the Environment 
Added experience and safety 
information in Health Care Workers 
(HCW) to support the inclusion of 
HCW in the trial 
8 
4.0 
17 
September 
2019 
Dr. J Langley Title Page. Correction of Investigator 
degrees. 
8 
4.0 
17 
September 
2019 
Dr. J Langley Section 5.1.3. Exclusion criteria. 
Revised to allow enrolment of 
participants with screening hematologic 
and chemistry values outside of normal 
site reference ranges, if deemed not 
clinically significant by the clinical 
investigator. In this study local normal 
reference ranges are used to determine 
eligibility. FDA Guidance for Industry 
Toxicity Grading Scales (Appendix 2), 
which are directed at healthy 
populations, are not applicable as the 
target population has HIV infection. 
The following five screening parameters 
will have limits set, and other values are 
assessed by the clinical investigator as 
clinically significant (and thus 
exclusionary) or not clinically 
significant: 
1. absolute lymphocyte count 
≥1000 cells/mm3 

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2. hemoglobin not greater than 1.5 
grams below the lower limit of 
the normal reference range at the 
local laboratory  
3. ALT, AST not greater than 2 to 
2.5 times the upper limit at the 
local laboratory 
4. Platelet count ≥ 125,000 and ≤ 
550,000 
 
8 
4.0 
17 
September 
2019 
Dr. J Langley Section 6.0. Trial Flow Chart and 
Section 7.1.3. Cohort 5 laboratory tests , 
and Section 8.2.3.1. Analysis endpoints, 
revised to delete HIV RNA reservoir 
testing and biobank samples, and 
correct total sample volumes. 
8 
4.0 
17 
September 
2019 
Dr. J Langley Section 7.1.5.1.  
Clarified that to exclude transient 
laboratory abnormalities the investigator 
may repeat a specific Screening test (E.g. 
hemoglobin) once during the screening 
period (E.e. a maximum of two tests) 
during the screening period. Clarified 
that a participant who is not eligible for 
an earlier cohort may be screened for 
eligibility for a subsequent cohort. 
 
8 
4.0 
17 
September 
2019 
Dr. J Langley Section 7.1.3. Laboratory/ 
procedures/assessments. Removed 
Urinalysis - specific gravity to align 
with 5.1.3. Inclusion and exclusion 
criteria. Removed 
 
 
 
 
 
 
No modification of this protocol will be allowed unless discussed and approved by the Coordinating 
Investigator and a filed and approved change to the protocol is submitted to and approval received 
from the local REBs.  Any administrative changes or amendments to this protocol will be adhered to 

25 
 
 
CT14B_ACHIV-Ebola Protocol Version 4.0 
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by all participating centres and will apply to all participants. Documentation of amendments and 
REB approvals will be maintained at each centre 
1.0 TRIAL SUMMARY 
Short Title: 
A Phase 2 Study of V920 Ebola Virus Vaccine Candidate in HIV 
Infected Adults and Adolescents 
Manufacturer Product 
Identifier 
V920 
Trial Phase 
Phase 2 
Clinical Indication 
Prevention of Ebola Disease 
Trial Type 
Randomized, multi-center 
Type of control 
Placebo 
Route of administration 
IM 
Trial Blinding 
Double blind 
Select Cohorts 
 
HIV-infected individuals within each of the five cohorts will be 
randomly assigned to receive V920 or placebo: 
Cohort 1: 50 adults with CD4 ≥ 500 cells/mm^3 
Cohort 2: 50 adults CD4 > 350 and < 500 cells/mm^3 
Cohort 3: 50 adults CD4 ≥ 200 and ≤ 350 cells/mm^3 
Cohort 4: 50 adolescents CD4 ≥ 200 cells/mm^3 
Cohort 5: 50 adults and adolescents CD4 ≥ 200 cells/mm^3 
Number of trial subjects 
Approximately 250 subjects will be enrolled. 
 
Estimated duration of trial 
The Sponsor estimates that the trial will require approximately 30 
months from the time the first subject signs the informed consent until 
the last subject’s last study-related phone call or visit.  
 
Duration of Participation 
Each subject will participate in the trial for approximately 13 months, 
from the time the subject signs the Informed Consent Form (ICF) 
through the final contact.  After a screening phase of up to one month, 
each subject in Cohorts 1 to 4 will be receiving one dose of assigned 
vaccine/placebo and each subject in Cohort 5 will be receiving one 
dose of assigned vaccine/placebo at Day 0, and followed by a second 
dose of the same vaccine/placebo treatment at Day 56.  Each subject 
will be followed for 365 days from the first vaccination. 
 
Randomization Ratio 
200:50 (4:1) 
 
 
 
A list of abbreviations used in this document can be found in Section 12.0. 

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2.0 TRIAL DESIGN 
2.1 
Trial Design 
This is a randomized, placebo-controlled, multi-site, double-blind trial of V920 (rVSVΔG-ZEBOV-
GP) Ebola Virus vaccine candidate in subjects with HIV infection to be conducted in conformance 
with Good Clinical Practices. The study will take place at 2 Canadian sites (Centre Hospitalier de 
l’Université de Montréal and Ottawa General Hospital) and 2 African sites (Centre MURAZ, Burkina 
Faso and Institut de Recherche en Santé, de Surveillance Epidemiologique et de 
Formations (IRESSEF), Dakar, Senegal).  The Duration of Study: 365 days for each participant not 
including screening. 
The study will enroll approximately 250 participants, ~100 at 2 sites in Canada and ~150 at 2 sites in 
Africa. Depending on recruitment rates, participants may be reallotted between sites in order to 
ensure the integrity of the study. Overall ~200 participants will receive the study vaccine and ~50 
will receive placebo.  Sequential enrollment of five study Cohorts will occur over time at each study 
site according to CD4 T-cell counts: Cohort 1 will include adult subjects with CD4 ≥ 500 cells/mm3, 
Cohort 2 CD4 > 350 and < 500 cells/mm3, Cohort 3 CD4 ≥ 200 and ≤ 350 cells/mm3, Cohort 4 
adolescents CD4 ≥ 200 cells/mm3, and Cohort 5 adults and adolescents with CD4 ≥ 200 cells/mm3 
receiving two doses 56 days apart. Enrollment and vaccine administration will begin with the cohort 
with the highest CD4 count. When the D42 post-vaccination period is completed for all subjects in 
Cohort 1, and the Data Safety Monitoring Board (DSMB) has reviewed the safety data and determined 
that there are no concerns, enrollment and vaccination of the next CD4 cohort may begin. Similarly, 
when the D42 safety data for Cohort 2 has been reviewed/approved by the DSMB, enrollment and 
vaccination of participants in Cohort 3 may begin.  Cohort 4 with adolescents 13-17 years of age 
(inclusive) with CD4 ≥ 200 will be enrolled after D42 safety is reviewed in adults with CD4 ≥ 200.  
Within each Cohort 1-4, participants will be randomly assigned to receive one dose of ≥2 x 107 pfu of 
the study vaccine or the placebo in a ratio of 4 to 1.  In Cohort 5, participants will be randomly assigned 
to receive one dose of ≥2 x 107 pfu of the study vaccine or the placebo in a ratio of 4 to 1, and followed 
by a matching vaccine or placebo dose at Day 56.  All participants will complete memory aids for 42 
days following each vaccination.  
Specific procedures to be performed during the trial, as well as their prescribed times and associated 
visit windows, are outlined in the Trial Flow Chart - Section 6.0. Details of each procedure are 
provided in Section 7.0 – Trial Procedures. 
This trial will use an adaptive design based on pre-specified criteria, using an independent, external 
DSMB to monitor safety.  There will be 4 formal safety analyses performed by the DSMB.  Data for 
at least 75% of participants must be available for each analysis. The first safety analysis will be 
conducted when the first Cohort (CD4 ≥ 500 cells/mm3) will have completed 42 days of follow-up 
post vaccination.  The second safety analysis will be conducted when the second Cohort (CD4 > 350 
and < 500 cells/mm3) will have completed 42 days of follow-up post vaccination. The third safety 
analysis will be conducted when the third Cohort (Adults CD4 ≥ 200 and ≤ 350 cells/mm3) will have 
completed 42 days of follow-up post vaccination. The fourth safety analysis will be conducted when 

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CT14B_ACHIV-Ebola Protocol Version 4.0 
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the fourth Cohort (Adolescents CD4 ≥ 200 cells/mm3) will have completed 42 days of follow-up 
post vaccination. 
Results of the safety analysis will be reviewed by the DSMB, which will make recommendations to 
the Sponsor to continue, modify or end the trial according to the plan described briefly in Section 
2.2 - Trial Diagram and in detail in Section 8.0 - Statistical Analysis Plan.  In case of an outbreak 
of Ebola Zaire the DSMB may recommend to vaccinate subjects randomized to receive placebo 
with V920 provided at least 84 days of SAE follow-up is conducted. 

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CT14B_ACHIV-Ebola Protocol Version 4.0 
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2.2 
Trial Diagram 
The trial diagram is depicted in Figure 1. 
Figure 1: Trial Diagram 
 
 

29 
 
 
CT14B_ACHIV-Ebola Protocol Version 4.0 
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3.0 OBJECTIVE(S) & HYPOTHESES 
3.1 
Primary Objective(s) & Hypotheses 
(1) 
Objective:  Evaluate the safety and tolerability of V920 in HIV-infected adults and 
adolescents. 
(2) 
Objective:  Evaluate the immunogenicity of V920 via ZEBOV- specific antibody 
responses induced by V920 in HIV-infected adults and adolescents. 
 
 
Primary Hypotheses:   
1) The geometric mean titer (GMT) of GP-ELISA in V920 vaccinated HIV-infected 
adults and adolescents will be superior to the GMT of the GP-ELISA in placebo 
vaccinated HIV-infected adults at Day 28 in Cohorts 1-5 combined.  
 
2) The geometric mean titer (GMT) of GP-ELISA in V920 vaccinated HIV-infected 
adults and adolescents will be superior to the GMT of the GP-ELISA in placebo 
vaccinated HIV-infected adults and adolescents Day 28 after the last dose of vaccine 
(equivalent to Day 84 from first dose) in Cohort 5 
3.2 
Secondary Objective(s)  
(1) 
Objective:  Evaluate VSV viremia and shedding after administration of V920. 
(2) 
Objective:  Evaluate ZEBOV-specific antibody responses induced by V920 through       
D180 and D365. 
(3) 
Objective: Evaluate the impact of V920 on HIV viral load, CD4 counts, and CD4/CD8 
ratio. 
(4) 
Objective:  Evaluate the safety and tolerability of two doses of V920 in HIV-infected 
adults and adolescents administered 56 days apart. 
(5) 
Objective:  Evaluate the immunogenicity of two doses of V920 administered 56 days 
apart via ZEBOV-specific antibody responses induced by V920 at D28 post-dose 2 in 
HIV-infected adults and adolescents. 
 
3.3 
Tertiary Objective(s)  
(1) 
Objective:  Evaluate Ebola-specific CD8 T cell responses 
(2)       Objective:  Evaluate B-cell repertoire 
(3)       Objective:  Evaluate the impact of V920 on HIV viral reservoir 
 

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4.0 BACKGROUND & RATIONALE 
4.1 
Background 
Refer to the Investigator’s Brochure (IB) for detailed background information on V920. 
Ebolaviruses (EBOV) are members of the Filoviridae and are known primarily as the 
underlying cause of severe viral hemorrhagic fevers with disturbingly high case fatality 
rates. Between 1994 and the present, there have been many EBOV outbreaks (refer Table 1) 
affecting mostly central Africa, with two large outbreaks in 1995 in Kikwit, DRC and in 
Gulu, Uganda in 2000-2001. 
 
The West African outbreak significantly exceeds all previous outbreaks in geographic range, 
number of patients affected and in disruption of typical activities of civil society 1. The West 
African Ebola outbreak was first recognized in Guinea, and then spread to Liberia and Sierra 
Leone, with a few imported cases resulting in some spreading in Nigeria, Mali, Senegal, 
U.S., UK and Spain. The vast majority of cases are from Guinea, Liberia and Sierra Leone. 
The epidemic peaked from Aug-2014 to Oct-2014, and as of 25-Nov-2015, it has caused 
over 28,000 reported cases and 11,000 deaths reported by the WHO (Figure 2). 
 
The disease affects both adults and children, although most cases are aged 20 to 50 years. The 
incubation period ranges from 2 to 21 days, with an average of 10 days in patients aged 16 to 
44 years, 11 days in patients aged 45 years or older, and a shorter average in children (7 days 
in children younger than 1 year and 10 days in children aged 10 to 15 years)2. 
 
Table 1: Ebolavirus Outbreaks 
 
Viral species 
Year 
Outbreak location 
# of human cases (% fatality) 
Zaire Ebolavirus 
1976 
Yambuku, Zaire (DRC) 
318 (88%) 
1977 
Tandala, Zaire (DRC) 
1 (100%) 
1994 
Ogooue-Invindo province, 
Gabon 
51 (60%) 
1995 
Kikwit, Democratic Republic of 
Congo 
315 (79%) 
1996 
Mayibout, Gabon 
37 (57%) 
1996 
Booue, Gabon and 
Johannesburg, South Africa 
61 (74%) 
2001-02 
Ogooue-Invindo province, 
Republic of Congo 
124 (79%) 

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CT14B_ACHIV-Ebola Protocol Version 4.0 
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2002-03 
Cuvette region, RC and Ogooue- 
Invindo province, Gabon 
143 (90%) 
2003 
Mboma and Mbandza, Republic 
of Congo 
35 (83%) 
2005 
Etoumbi and Mbomo, Republic 
of Congo 
12 (75%) 
2007 
Kasai Occidental province, 
Democratic Republic of Congo 
249 (73%)) 
2008/2009 
Democratic Republic of the 
Congo 
32 (47%) 
2014  
Democratic Republic of the 
Congo 
66 (72%) 
2014-2016 West Africa including Guinea, 
Sierra Leone, Liberia 
28,652 (40%) 
2017  
Democratic Republic of the 
Congo 
17 (23%) 
Sudan Ebolavirus 
1976 
Nzara, Maridi, Tembura, Juba, 
Sudan 
284 (53%) 
1979 
Nzara, Yambio, Sudan 
34 (65%) 
2000-01 
Gulu, Masindi, Uganda 
425 (53%) 
2004 
Yambio, Sudan 
17 (41%) 
2011 
Uganda (Luwero District) 
1 (100%) 
Taï Forest  
1994 
Tai forest, Ivory Coast 
1 (0%) 
 
1995 
Liberia, Liberia 
1 (0%) 
Reston Ebolavirus 
1989 
Reston, USA 
4 (0%) 
1992 
Siena, Italy 
0 
1996 
Alice, Texas 
0 
2008 
Phillipines 
0 
Bundibugyo 
Ebolavirus 
2007/2008 
Uganda 
131 (37%) 
 
 
 

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Figure 2: Total suspected, probable, and confirmed cases of Ebola virus disease in Guinea, 
Liberia, and Sierra Leone, March 25, 2014-February 14, 2016, by date of WHO Situation 
Report, n=28603. 
 
By WHO Situation Report 
Source: http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/cumulative-cases-
graphs.html 
 
Therapies for Filovirus infections 
 
Treatment of Ebola hemorrhagic fever is mainly supportive, involving fluid and electrolyte 
replenishment and pain reduction. Specific treatments are under development. Convalescent 
plasma was used in a limited number of patients during the Kikwit 1995 ZEBOV outbreak, but 
its success was disputable3. Passive immunization with hyperimmune horse serum delayed but 
did not prevent death in cynomolgus macaques4,5. Monoclonal antibody treatment was 
successful in rodent models, but failed in preliminary NHP studies, indicating a possible 
evasion of antibody neutralization6-9. All of the abovementioned studies used single 
monoclonal antibody clones, which may not be sufficient to control infection. 
 
During the recent outbreak, experimental therapies including a cocktail of 3 monoclonal 
antibodies (ZMapp, Mapp Biopharmaceutical), lipid encapsulated siRNA (small interfering 
RNA, TKM-Ebola, Tekmira Pharmaceuticals Corp), and two antiviral drugs (brincidofovir and 
favipiravir) have been employed in individual patients. Although the efficacy of these 
treatments in these patients is not clear, they have been shown to be successful in animal 

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CT14B_ACHIV-Ebola Protocol Version 4.0 
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studies. Treatment with the optimized ZMapp cocktail rescued 100% of rhesus macaques when 
treatment was initiated up to 5 days after lethal EBOV challenge10. The Tekmira siRNA 
product similarly showed high-grade protection against lethal filovirus infection when NHP 
were treated up to 3 days after challenge11. The rVSVΔG-ZEBOV-GP vaccine may also play 
an important role in preventing the onset of the Ebola virus disease (EVD) in situations where 
the precise time of exposure were known, and the vaccine could be applied early after 
exposure. 
A preventive vaccine, in contrast, could be used to protect individuals at high risk in advance 
of exposure, such as persons traveling to or residing in endemic or epidemic settings, and could 
be used for outbreak control at a population level to interrupt transmission. Since the rVSVΔG- 
EBOV-GP vaccine elicits rapid and likely durable immunity after a single dose, it has 
important potential for use in this context, as well as for the indication of post-exposure 
prophylaxis after recognized, high-risk exposure. 
 
Vesicular stomatitis virus as a vaccine vector 
 
VSV belongs to the family Rhabdoviridae, genus Vesiculovirus. These are bullet-shaped, 
single-stranded, negative-sense RNA viruses containing five genes, one of which is the viral 
GP. In the U.S., the two most common serotypes are VSV-New Jersey and VSV-Indiana. VSV 
cause significant disease in pigs, cattle, and horses, primarily manifesting as crusting and 
vesiculation of the mucous membranes and skin, and lameness due to involvement of the 
coronary bands of the hoof. The virus is maintained in nature in a cycle involving sandflies 
and rodent reservoirs. It is also transmitted between livestock by direct contact, likely including 
droplet spread and fomites, as well as mechanically by non-biting houseflies and face flies. 
Pre-existing immunity to VSV is not prevalent in humans in the U.S., and VSV does not 
circulate outside the Western Hemisphere; therefore it is not expected to be a significant factor 
in a potential vaccination campaign in the U.S. or in parts of Africa with VSV-based vaccines. 
Moreover, in VSV vaccines where the viral GP is replaced with GPs of other viruses, the 
impact of pre-existing anti-VSV neutralizing antibodies is theoretically minimized. 
 
VSV virus can be transmitted to humans who come in close contact with infected animals. The 
incubation period is most commonly 3 to 4 days. The most common clinical manifestation is 
a limited, 3- to 5-day flu-like illness. In rare cases, humans can manifest vesicles on the 
oropharyngeal, nasal mucosa or skin. Human deaths secondary to infection have not been 
reported; however, encephalitis was reported in a single case of a 3-year old child secondary 
to VSV-Indiana infection12 . As there is only one case report in the literature, the risk of central 
nervous system infection following VSV infection is undoubtedly rare. In some areas of 
tropical America, a high seroprevalence to VSV has been reported without recognized 
disease13 . Thus, it is likely that the ratio of infection to illness with VSV is high. 
 
The V920 construct used in the clinical trials was derived from the VSV-Indiana serotype. As 
described above, the rVSV-based vector used in this vaccine lacks the VSV GP, the viral 
determinant for neurotropism and pathogenicity14-16, rVSVΔG-ZEBOV-GP has approximately 
33% slower growth kinetics than wild-type VSV in Vero cell cultures, contributing to 

34 
 
 
CT14B_ACHIV-Ebola Protocol Version 4.0 
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attenuation17. The rVSVΔG-ZEBOV-GP virus is apathogenic for hamsters, whereas wild-type 
VSV is lethal in hamsters after peripheral inoculation (Feldmann H., unpublished data, 2014). 
4.1.1 Pharmaceutical and therapeutic background 
rVSVΔG-ZEBOV-GP AS A CANDIDATE VACCINE FOR EBOLA ZAIRE DISEASE 
 
The rVSVΔG-ZEBOV-GP vaccine is a live attenuated recombinant virus consisting of a single 
recombinant VSV isolate (11481 nt, strain Indiana) with the gene for the Zaire ebolavirus GP 
(ZEBOV GP), Kikwit strain replacing the gene for the VSV GP, which has been deleted. This 
results in a VSV backbone with the ZEBOV GP constituting the envelope of the virus. As for 
similar chimeric vaccines, the substitution of the native virus GP genes with a heterologous 
GP leads to significant attenuation of a virus18. The ZEBOV GP on the surface of the virus 
may narrow the cell tropism of the recombinant virus. The substitution of the heterologous 
Ebolavirus GP does not perturb the proper assembly of the virus particle, and the recombinant 
vaccine resembles the native VSV bullet structure in electron micrographs (Figure 3). Refer to 
the Investigator’s Brochure (IB)/approved labeling for detailed background information on 
V920. 
Figure 3: (A) A single-stranded, negative-sense RNA encoding 5 transcriptional units: N 
(nucleoprotein), P (phosphoprotein), M (matrix), G (glycoprotein), and L (polymerase). 
rVSVΔG-ZEBOV-GP was generated by deleting the VSV G gene and inserting the ZEBOV 
GP gene in the new transcriptional unit after the VSV M gene. (B) Electron micrograph of 
the WT VSV and rVSVΔG-ZEBOV-GP. 
 
 
 
 
 

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4.1.2 Pre-clinical Trials 
Immunogenicity as well as pre- and post-exposure prophylactic efficacy of VSVΔGZEBOV-
GP, has been demonstrated following a single IM injection in multiple nonclinical studies in 
rodent species and nonhuman primates (NHP). Briefly, vaccination of mice with a single 
intraperitoneal (IP) injection of as few as 200 plaque-forming units (pfu) of VSVΔGZEBOV-
GP provided 100% protection against lethal mouse-adapted ZEBOV challenge 28 days after 
immunization19. Similarly, a single intramuscular (IM) vaccination of cynomolgus macaques 
with rVSVΔG-ZEBOV-GP induced strong and long-lasting humoral and cellular  immune 
responses20 and 100% protection against a lethal IM challenge of homologous ZEBOV given 
by the IM route 28 days later16 or by aerosol21. Protection from aerosol challenge has not been 
replicated in more recent studies and vaccinated animals experienced pulmonary inflammation 
with significant lung pathology; the reasons for this are being studied further.  Additionally, a 
single IM injection of rVSVΔG-ZEBOV-GP protected macaques against lethal IM challenge 
with the West African EBOV-Makona strain, with complete protection achieved against 
challenge 7 days post vaccination and partial protection at 3 days post vaccination22. In a post- 
exposure prophylaxis model, 50% of NHP vaccinated within 30 minutes after a severe (1000 
median lethal dose [LD50]) aerosol EBOV challenge survived23. 
 
Various studies in animal models have shown no toxicities in rodent or NHP models, including 
in immunocompromised NHP24; particularly noteworthy was the absence of neurovirulence in 
NHP following intrathalamic inoculation15. Current Good Laboratory Practice (cGLP) 
repeated dose toxicology studies are ongoing to evaluate the toxicity and local tolerance of 
V920 in mice and monkeys. In these studies V920 was administered via IM injection on Study 
Days 1 and 14 followed by a 30-day observation period. BALB/c mice and cynomolgus 
monkeys received V920 at up to 2.0×107 pfu/animal and 1.0×108  pfu/animal, respectively. To 
date, there has been no evidence of systemic toxicity based on preliminary clinical pathology 
and necropsy data. 
 
4.1.3 Ongoing Clinical Trials 
Eight Phase 1 and four Phase 2/3 clinical trials are ongoing. The Phase 1 studies have been 
undertaken in North America (U.S. and Canada), Europe (Switzerland and Germany), and non- 
epidemic regions of Africa (Gabon and Kenya) to evaluate the immunogenicity and safety of 
V920 administered as pre-exposure prophylaxis.  The four late phase studies include (1) a 
Phase 2 placebo-controlled trial in Liberia25, (2) a Phase 3 trial in Sierra Leone with early and 
delayed vaccination arms, (3) a Phase 3 ring vaccination trial in Guinea, and (4) a Phase 3 
immunogenicity, safety, and consistency lots trial in North America and Europe. Robust 
antibody responses to the ZEBOV-GP (with 100% of subjects seroconverting by 28 days) have 
been noted both by the enzyme-linked immunosorbent assay (ELISA) and virus neutralization 
assays in the Phase 1 program. After qualification and validation, these assays will be used to 
assess the antibody responses from subjects in the Phase 2/3 studies.  If one assay is found to 
be sufficient to characterize the immune response, use of the assay that does not add value may 
be discontinued.  
 

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Preliminary efficacy and effectiveness data have been assessed in an interim analysis of ring 
vaccination trial in Guinea 26. Per the publication, 7,651 subjects were included in the planned 
interim analysis which included 48 clusters (4,123 subjects) randomly assigned to immediate 
vaccination with V920 (2x107 pfu), and 42 clusters (3,528 subjects) randomly assigned to 
delayed vaccination with V920 (2x107 pfu). In the immediate vaccination group, there were 
no cases of EVD with symptom onset at least 10 days after randomization, whereas in the 
delayed vaccination group there were 16 cases of EVD from seven clusters reported, 
demonstrating a vaccine efficacy of 100% (95% CI: 74.7, 100.0; p=0.0036). At the cluster 
level, with the inclusion of all eligible adults, vaccine effectiveness was 75.1% (95% CI: 7.1, 
94.2; p=0.1791). No new cases of EVD were diagnosed in vaccines from the immediate or 
delayed groups from 6 days post vaccination. 
 
4.2 
Rationale 
4.2.1 Rationale for the Trial and Selected Subject Population 
Future Ebola outbreaks are likely to occur in countries where HIV infection is endemic or 
present in large segments of the population.  It is important to know whether V920 will be safe 
and effective in this patient population as efforts to roll out vaccination during an epidemic 
need to be quick and HIV testing may not be possible.  Twenty two known HIV-infected 
individuals have received V920 in the Phase 2 placebo-controlled trial in Liberia, and the 
preliminary safety profile in this small number of subjects appeared to be generally similar to 
the overall vaccinated population.  However, safety and immunogenicity of V920 has not been 
formally evaluated in HIV-infected individuals in a randomized controlled manner to date.  
This is what is intended with this study. 
Persons 65 to 70 years were initially excluded and subsequently included as there are a number 
of potential participants in this age group who are interested in participating. The risk of 
including this age group is the risk that poor immunogenicity could be attributed to vaccine 
rather than to immunosenescence in this age group and that older HIV positive subjects may 
have a different safety profile. However, it is unlikely that immune and safety responses will 
be remarkably different in 60 to 65 year old subjects (who are currently eligible) compared to 
66 to 70 year old subjects who will become eligible. To date over 400 non-HIV infected 
subjects over 65 years of age have been enrolled in clinical trials and safety concerns in this 
age group have not been identified to date.  Detailed analyses of age strata >65 years of age 
are ongoing. 
 
4.2.2 Rationale for Dose Selection/Regimen/Modification 
4.2.2.1 Rationale for the Use of Placebo Control  
The use of placebo control will allow for comparison of safety and immunogenicity against an 
inert substance (normal saline).  It is ethical to use normal saline in this study as Ebola is not 
circulating in areas where the study will be conducted. If an Ebola outbreak were to occur and 
local public health authorities recommended Ebola vaccination then placebo participants could 

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choose to receive an Ebola vaccine. Local public health guidance in each study site would be 
followed.  
 
4.2.2.2 Vaccine Dose for This Trial 
One dose of ≥2 x 107 pfu of the study vaccine or placebo will be administered at D0 in all Cohorts.  
In Cohort 5, a second dose of matching vaccine (≥2 x 107 pfu/ml) or placebo will be administered 
at Day 56. The rationale for assessing a second dose in HIV positive subjects is to access whether 
a second dose will provide a greater immune response or a response in a greater proportion of 
subjects in case one dose is less immunogenic in HIV positive subjects than in non-HIV positive 
subjects assessed in other studies.  The 56 day interval is based on the interval utilized in other 
studies that include non-HIV positive adults and children. 
4.2.3 Rationale for Endpoints 
4.2.3.1 Immunogenicity Endpoints 
1.    Primary endpoints: 
a.  ZEBOV-specific antibody responses measured by ELISA and neutralization 
on Day 28 in Cohorts 1-5 combined. 
b. ZEBOV-specific antibody responses measured by ELISA and neutralization 
on Day 28 after the last dose of vaccine (equivalent to Day 84 from first dose) 
in Cohort 5. 
2. Secondary endpoints: 
a. ZEBOV-specific antibody responses measured by ELISA and neutralization 
on Day 28 in Cohort 5. 
b.  ZEBOV-specific antibody responses measured by ELISA and neutralization 
on Days 180 and 365 after the first dose of vaccine.  
 
The V920 vaccine candidate is a live recombinant vesicular stomatitis virus (VSV) expressing 
the glycoprotein (GP) of Zaire Ebola virus (ZEBOV). Two independent assays are currently 
being utilized in the clinical development program to clinically evaluate the immunogenicity 
of V920: 
▪ GP-ELISA measures the total IgG antibody response and can also be correlated to the 
plaque reduction neutralization assay (PRNT) titer result. 
▪ Plaque reduction neutralization assay (PRNT) is a functional assay and a gold standard 
platform in the field for quantitating the neutralizing antibody response elicited by the 
vaccine.  
If in the clinical development program one assay is found to be sufficient to characterize the 
immune response, use of the assay that does not add value may be discontinued. 

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4.2.3.2 Safety Endpoints 
1. Primary endpoints: 
a. The occurrence of adverse events, in all participants, in all cohorts: 
i. The occurrence of each solicited local and systemic AE, during a 14-
day follow-up period following each vaccination, and fever, arthritis, 
arthralgia, rash and blisters/vesicular lesions during a 42-day follow –
up period following vaccination. 
ii. The occurrence of any hematological (hemoglobin level, WBC, 
lymphocyte, neutrophil, eosinophil and platelet count) and 
biochemical (ALT, AST and creatinine) laboratory abnormality at 
days 0, 3, 7, 14, and 28 after each vaccination.  
iii. The occurrence of any unsolicited AE, during a 42-day follow-up 
period after each vaccination.  
b. The occurrence of vaccine related SAE through to Day 365. 
 
2. Secondary endpoints: 
a. Detection of rVSV by PCR in blood, urine, and saliva in all subjects (D3, 7, 
14, 28, 42 following each vaccination) 
b. Detection of rVSV by PCR in through 42 days from skin vesicles, joint fluid, 
or skin biopsies if specimens are obtained  
c. The occurrence of any SAE through to Day 365 
d. Decrease in CD4 T cell-count ( i.e., CD4< 200 mm3) 
e. Increase in HIV viral load (i.e., VL > 50 c/ml over two consecutive 
measurements) 
Adverse events are collected 42 days post-vaccination for live-attenuated vaccines because of 
the time required for viral replication and manifestation of adverse events. The Memory Aid 
will prompt the subject to record his/her temperature for 42 days following vaccination starting 
with the day of vaccination (D0-D42). Injection site and systemic reactions will be monitored 
on the day of vaccination (D0) and for 14-days post-vaccination (D1-D14). In addition subjects 
will be prompted for joint pain, joint swelling, rashes, and blisters or vesicular lesions during 
the 42-day post-vaccination period as these events have been reported in the development 
program. Subjects who demonstrate these symptoms may be asked to return to the study site 
for additional evaluation and work-up. All other unsolicited systemic and/or injection-site 
adverse events will be recorded during the 42-day post-vaccination period.  Following the 42-
day detailed safety reporting period, any serious adverse events (SAEs) that occur through 12 
months after first vaccination are to be reported in order to provide long-term safety data.  
Safety laboratory data is obtained through Day 42, as in Phase 1 studies transient decreases in 
white blood cells and platelets have been assessed for 28 days in HIV- subjects.  
 
4.3 
Benefit/Risk 
Subjects in clinical trials generally cannot expect to receive direct benefit from 
treatment/vaccination during participation, as clinical trials are designed to provide 
information about the safety and effectiveness of an investigational medicine.  

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Potential risks may include those common to other vaccine products, and include local 
injection site reactions, as well as systemic reactions.  The following sections discuss these 
potential risks in more detail and include brief descriptions for possible procedures to 
ameliorate risks and symptoms. All known risks and precautions described are explained in 
detail in the informed consent document.  For live-attenuated vaccines such as V920 it is 
expected that the second dose of vaccine will have fewer safety concerns than the first dose 
of vaccine as the immune response from the first dose decreases viral replication.   
 
4.3.1 Risks 
4.3.1.1 Local Reactions  
Local reactions, with either V920 or placebo, may include pain, swelling, and/or redness at 
the injection site.  Although highly unlikely, IM injections, independent of investigational 
product, can result in acute muscle damage, bruising, and/or injection site infection. 
Vaccine will be administered by experienced and trained staff, using aseptic technique, in 
order to minimize or avoid these risks. 
 
4.3.1.2 Systemic Reactions 
Systemic reactions include a predictable period of early reactogenicity which is common 
after receipt of other live-virus vaccines, and resolves spontaneously. On occasion, 
individuals may feel light-headed or faint after the act of injection or blood draw 
(vasovagal reaction). 
Monitoring for these and other systemic symptoms commonly seen in investigational 
vaccine studies will be performed throughout the study, and addressed as required in order 
to maximize subject safety. 
There is a theoretical risk of viral encephalitis or neurological impairment following 
vaccination with rVSV.  As described previously, the vaccine vector has been specifically 
attenuated to eliminate neurovirulence, and the aforementioned NHP neurovirulence study 
supports the efficacy of this approach.  Subjects will be closely monitored for vaccine 
neurological impact during the study. 
Wild type VSV may also cause mild oral ulceration or stomatitis in humans. Volunteers will 
be closely monitored for such a manifestation and oral swabs will be performed to monitor 
for viral shedding in association with such a manifestation. 
 
4.3.1.3 Reactions to V920 
Detailed safety data collected in the Phase 2 and 3 studies to date have demonstrated V920 to 
be generally well-tolerated when administered to healthy, non-pregnant, adults. Injection site 
reactions following vaccination are generally mild to moderate and self-limited. Thereafter, 
there is a predictable period of early reactogenicity, including fever and a flu-like syndrome 
and resolves with 7 days. During this time, transient decreases in white blood cells and platelets 

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have also been observed but bleeding or increased risk of infection has not been reported. The 
early reactogenicity is likely to be a result of viremia with the vaccine virus which resolves 
within 2 weeks. Vaccine virus has been found in saliva, urine, and skin-vesicles in vaccines.  
Person-to-person transmission has not been documented, however transmission through 
shedding and close personal contact is accepted as a theoretical possibility. Joint pain 
(arthralgia) is part of the early flu-like syndrome in the first week after vaccination in up to 
44% of vaccines. In a small proportion of subjects (<5%), joint swelling (arthritis) may develop 
in the 2nd to 3rd week after vaccination. The arthritis is thought to be virally-mediated, and 
while the majority of arthralgia and arthritis events resolved spontaneously, recurrent or 
persistent arthralgia and arthritis have also been reported. The safety profile reported from the 
Ebola-epidemic region has been similar to that observed outside the region.  
 
4.3.1.4 Pregnancy 
Risks from the study vaccines to human fetuses are unknown at this time. As such, pregnant 
females will be excluded from participation. All female subjects of childbearing potential 
must be abstinent from intercourse with a male partner or utilize effective contraceptive 
precautions, as defined in the inclusion criteria (section 8.4), from 30 days prior to the date 
of vaccination through 2 months after the last vaccination. Non-childbearing potential is 
defined as either surgically sterilized or one year post-menopausal (defined as 12 
consecutive months without menses). 
Given the theoretical risk of transmission to a female partner of child bearing potential, male 
subjects will also be required to utilize effective contraception precautions for the same 
period of time. 
 
4.3.1.5 Lactation 
Risks from the study vaccines to nursing infants are unknown at this time. As such, 
breastfeeding females will be excluded from participation, and female subjects will be 
required to avoid breastfeeding during the study to minimize any potential risk. 
 
4.3.1.6 Venipuncture 
Some discomfort from the needle stick for the blood draw is possible, including swelling or 
bruising, and there is a very small risk of infection at the site of the needle stick. A few 
subjects may feel light-headed and may develop a rapid heartbeat during blood collection. 
These symptoms can be stopped by having the subject lie down and/or by stopping the 
procedure. 
 
4.3.1.7 Allergic Reaction 
As with any product, there is the potential risk of a serious, or even life-threatening, allergic 
reaction to one or more components of the investigational products to be used in this study. 
To mitigate this risk, potential subjects with a history of severe allergic reaction of any kind, 

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or significant allergic reaction to a known component of the experimental products, will be 
excluded from participation. 
In the event of a severe allergic reaction, each study site is staffed with trained medical 
personnel and stocked with appropriate medical emergency equipment to provide acute care 
for conditions such as anaphylaxis. Further, a formal emergency medical response service 
at each study site, capable of treating and transferring any life-threatening injuries to a higher 
level of medical care, will be available. 
 
4.3.1.8 Unknown Risks 
Furthermore, as with all research there is the remote possibility of risks that are unknown or 
that cannot be foreseen based on available information. This would include late effects that 
have been seen with some vaccines. 
At the time of writing the protocol, the V920 study vaccine has been given to >20,000 
participants in clinical trials in Africa.  Serious adverse event reporting is monitored in real 
time in a blinded fashion.  Un-blinded interim analyses have been performed in several 
trials. 
 
4.3.1.9 Risks to the Study Personnel and the Environment  
The principal risk for study personnel is exposure in the clinical setting to infectious 
pathogens from study subjects through various contact mechanisms (eg, needle stick 
exposure to blood borne pathogens and exposure to respiratory pathogens). There is also the 
theoretical risk of transmission of vaccine vector (rVSV) through exposure to shed vaccine 
in blood or body fluids.  Adherence to routine practices and additional precautions and 
standard operating procedures (SOPs) for working with infectious agents will reduce the 
risk of exposure. 
There are no known risks to the environment other than those associated with the generation 
of biohazardous waste attendant to vaccination of humans. All biohazardous waste will be 
disposed of as stipulated by local, state, and federal regulations and in accordance with study 
site SOPs. 
 
Health Care Workers (HCW) were initially excluded and subsequently included in order to 
increase recruitment.  During the original design of the trial HCWs were excluded because of 
the theoretical possibility that HIV infected persons would be more likely to shed vaccine 
vector following immunization due to their immune-compromise. Since that time accumulated 
evidence does show transient vector viremia but no evidence of transmission of the VSV 
vector. All study participants are given guidance about use of infection prevention and control 
measures and use of personal protective equipment to prevent sharing of secretions. It is 
anticipated therefore that the risk of a participant’s VSV vector being transmitted to the persons 
they care for is very low. Health care workers are enrolled in other V920 studies and given 
guidance about infection prevention and control measures.  
 

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4.3.2 INTENDED BENEFIT FOR SUBJECTS 
There is no intended direct benefit for study subjects. Subjects will receive a general health 
care screening as part of their participation in the study, and these results may be shared 
with their health care provider for their medical care, if permission of the participant is 
given.   It is possible that vaccination with V920 may result in an immune response to 
Ebola virus. The protective efficacy of such a response is unknown.  
Additional details regarding specific benefits and risks for subjects participating in this 
clinical trial may be found in the accompanying Investigators Brochure (IB) and Informed 
Consent documents. 
5.0 METHODOLOGY 
5.1 
Entry Criteria 
5.1.1 Diagnosis/Condition for Entry into the Trial 
Male/Female subjects with HIV-infection at least 13 years of age will be enrolled in this trial. 
5.1.2 Subject Inclusion Criteria 
To be eligible for the study, each participant must satisfy ALL of the following criteria: 
 
1) HIV-infected adult or adolescent male or non-pregnant, non-breastfeeding 
female, ages 13 to 70 (inclusive) at the time of screening; 
2) On antiretroviral therapy with an undetectable viral load (< 40 c/ml); 
3) CD4 T cell counts ≥ 200 cells/mm3; 
4) Written informed consent (subject or parent) and assent (adolescent), after 
reading the consent form and having adequate opportunity to discuss the study 
with an investigator or a qualified designee 
5) Free of clinically significant health problems that could affect the safety of the 
participant, as determined by the Investigator by pertinent medical history and 
clinical examination prior to entry into the study; 
6) Available, able, and willing to participate for all study visits and procedures; 
7) Males and females who are willing to practice abstinence from sexual intercourse, 
or are willing to use effective methods of contraception, from at least 30 days prior 
to vaccination until 2 months after vaccination. 
a. If the partner is NOT of childbearing potential, the couple will only be 
required to use condoms, without other adjunctive contraception. 
b. For this study, a woman is considered of childbearing potential unless 
postmenopausal (≥ 1 year without menses) or surgically sterilized (tubal 
ligation, bilateral oophorectomy, or hysterectomy) 
c. Effective contraception is defined as a contraceptive method with failure 
rate of less than 1% per year when used consistently and correctly and 
when applicable, in accordance with the product label for example: 
i. Male condoms PLUS: 

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ii. Oral contraceptives, either combined or progestogen alone 
iii. injectable progestogen 
iv. implants of etenogestrel or levonorgestrel 
v. oestrogenic vaginal ring 
vi. percutaneous contraceptive patches 
vii. intrauterine device or intrauterine system 
 
8) Be willing to minimize blood and body fluid exposure of others for 8 weeks after 
vaccination 
a. Avoiding the sharing of needles, razors, or toothbrushes 
b. Avoiding open-mouth kissing 
 
5.1.3 Subject Exclusion Criteria 
Participants with any of the following criteria will be excluded: 
 
1. History of prior infection with a filovirus or prior participation in a filovirus vaccine 
trial; 
2. History of prior infection with VSV or receipt of a VSV-vectored vaccine; 
3. Presence of any febrile illness or any known or suspected acute illness on the day of 
any first immunization (subject may be rescheduled);  
4. Clinical manifestations of systemic diseases considered by the investigator to impact 
safety or immunogenicity 
5. Receipt of systemic glucocorticoids (a dose ≥ 20 mg/day prednisone or equivalent) 
within one month, or any other cytotoxic or immunosuppressive drug within 12  
months; 
6. Receipt of any investigational drug within 12 months of vaccination; 
7. Receipt of any live virus vaccine within 42 days prior to study entry or any other (non-
live virus) vaccine within 14 days prior to study entry. 
8. History of sensitivity to any component of study vaccines per investigator brochure or 
package insert; 
Any baseline laboratory screening tests which is outside of acceptable range as defined 
in the protocol (local site reference ranges): ALT, AST, creatinine, hemoglobin, platelet 
count, total white blood cell count, urine protein, urine occult blood, urine glucose AND 
considered clinically significant by the clinical investigator. The following five screening 
parameters have limits set: 
a. absolute lymphocyte count ≥1000 cells/mm3 
b. hemoglobin not greater than 1.5 grams below the lower limit of the normal reference 
range at the local laboratory  
c. ALT, AST not greater than 2 to 2.5 times the upper limit at the local laboratory 

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d. Platelet count ≥ 125,000 and ≤ 550,000 
 
9. To exclude transient laboratory abnormalities, the investigator may repeat a specific 
test (E.g. hemoglobin) once during the screening period (I.e. a maximum of two tests), 
, and if the repeat test is normal, subject may be enrolled; 
10. Have an active malignancy or history of metastatic or hematologic malignancy except 
non-melanoma skin cancers; 
11. Suspected or known alcohol and/or illicit drug abuse within the past 5 years; 
12. Moderate or severe illness and/or fever >101°F (38.3ºC) orally or > 100°F (37.8ºC) 
axillary within one week prior to vaccination; 
13. Pregnant or breastfeeding female, or female who intends to become pregnant during 
the study period; 
14. Administration of immunoglobulins and/or any blood products within the 120 days 
preceding study entry or planned administration during the study period; 
15. Any other significant finding that in the opinion of the investigator would increase the 
risk of the individual having an adverse outcome from participating in this study. 
5.2 
Trial Vaccination 
The vaccines to be used in this trial are outlined below in Table 2: 
 
Table 2: Trial Treatment/Vaccination 
Vaccine 
Dose/Potency 
Dose 
Frequency 
Route of 
Administration 
Regimen/Treatment 
Period/Vaccination 
Regimen 
Use 
V920 
 
≥2x107 PFU in 
1mL 
Once in 
cohorts 1-
4/Twice in 
Cohort 5 
 
IM 
 
Visit 1, D0 and Visit 
7 (Day 56), where 
applicable 
Experimental 
 
Normal 
saline 
(0.9%) 
1 ml 
Once in 
cohorts 1-
4/Twice in 
Cohort 5 
 
IM 
Visit 1, D0 and Visit 
7 (Day 56), where 
applicable 
Placebo-
control 
Subjects in Cohort 5 will receive two doses of V920 ≥2x107 PFU or two doses of normal saline placebo 
(0.9%) on D0 and D56. 
Vaccination is given on the day of treatment allocation/randomization or as close as possible 
to the date on which the subject is allocated/assigned. 

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The vaccine dose will be administered at the trial site at Visit 1 (and Visit 7 for Cohort 5).  
Participants will be observed 30 minutes after vaccination to monitor for immediate 
hypersensitivity reactions. 
 
All products indicated in Table  above will be provided centrally by the Manufacturer or locally 
by the trial site, subsidiary or designee, depending on local country operational or regulatory 
requirements. 
For any commercially available product that is provided by the trial site, subsidiary or designee 
every attempt will be made to source these supplies from a single lot/batch number. The trial 
site is responsible for recording the lot number, manufacturer, and expiry date for any locally 
purchased product as per local guidelines unless otherwise instructed by the Sponsor. 
The investigator shall take responsibility for and shall take all steps to maintain appropriate 
records and ensure appropriate supply, storage, handling, distribution and usage of trial 
treatments in accordance with the protocol and any applicable laws and regulations. 
5.2.1 Formulation, Packaging, and Labeling of V920 
The rVSV∆G-ZEBOV-GP vaccine (V920) consists of a single recombinant VSV isolate 
modified to replace the gene encoding the G envelope glycoprotein with the gene encoding the 
envelope glycoprotein from Ebola virus-Zaire.  
The vaccine product is supplied in a sterile 1.0-mL vials. Each vial contains vaccine virus 
frozen in a mixture of 10mM Tris, pH 7.2 and recombinant human serum albumin 2.5 mg/mL. After 
thawing, the content of the vials is a clear liquid. The vaccine concentration in the vial is titered 
to at least 2x107pfu/mL (stock). 
5.2.2 Storage and Stability 
rVSV∆G-ZEBOV-GP vaccine product (V920) is to be stored at or below -60°C for long-
term storage. Storage temperature will be continuously monitored and recorded. Vaccine 
product will be stored in a locked room with access restricted to only necessary study site 
personnel. Vaccine should be stored and transported at temperatures at or below -60°C. 
Normal saline (0.9%) should be stored according to its labeling. 
 
5.2.3 Preparation, Administration, and Dosage of V920 
rVSV∆G-ZEBOV-GP vaccine (V920) will be administered as an IM injection. V920 should 
be removed from the freezer and thawed at room temperature (not 2-8°C) for approximately 
10-15 minutes. The thawed vial should then be gently inverted several times prior to 
withdrawal with the syringe. The study vaccine is considered to be thawed when there is no 
visible ice on the outside of the vial. The study vaccine should appear as a colorless liquid with 
no particulates visible. If the study vaccine appears cloudy or has particulates, a replacement 
vial should be assigned and administered. Once thawed in the clinic, a total cumulative of 15 
minutes at 25°C and/or 27 days at 2-8°C is permitted. Refreezing is not permitted by the end 
user. The formulation and/or image of the study vaccine and placebo control may appear 

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different. Therefore, an unblinded pharmacist (or other designated unblinded person) at the site 
will be required to prepare the study vaccine/placebo in order to maintain the blinding. The 
unblinded personnel will not participate in post-vaccination assessments.  Both study vaccine 
and placebo are clear, and indistinguishable from one another once in the syringe.  Once the 
syringe is prepared, the blinded personnel will administer the study vaccine/placebo to the 
subject. If V920 is administered, a dose of 2x107 pfu/mL will be given in a 1mL volume. Prior 
to injection, the area to be injected will be cleaned with an alcohol swab. 1.0 mL of study 
vaccine/placebo should be administered intramuscularly (IM) in the deltoid muscle of the non-
dominant arm at a 90º angle into the muscle tissue, using a needle long enough to ensure IM 
deposition of the study vaccine/placebo. A 1-inch #23-gauge needle is recommended. The 
vaccination arm must be recorded on the appropriate case report form for future reference in 
the event of potential injection-site reaction(s). Emergency medical supplies including 
epinephrine and advanced airway support will be available in case of serious allergic reaction. 
5.2.4 Dose Selection/Modification 
5.2.4.1 Dose Selection (Preparation) 
The rationale for selection of doses to be used in this trial is provided in Section 4.0 – 
Background & Rationale.  There are no specific calculations or evaluations required to be 
performed in order to administer the proper dose to each subject. 
5.2.5 Timing of Dose Administration   
All subjects will receive on D0 either the V920 (rVSVΔG-ZEBOV-GP) vaccine at a dose of 
≥2x107 PFU in 1mL IM, or normal saline (0.9%) placebo control in 1mL volume.  Subjects in 
Cohort 5 will also receive on D56 a matching dose of either the V920 at a dose of ≥2x107 PFU 
in 1mL IM, or normal saline (0.9%) placebo control in 1mL volume.  
5.2.6 Trial Blinding  
This is a double-blind trial; therefore, the Sponsor, investigator, and subject will not know the 
vaccine administered until unblinding.  
5.3 
Randomization or Treatment Allocation or Vaccine Allocation 
Subjects will be assigned randomly according to a computer-generated allocation schedule. 
Participants will be randomized 4:1 (study vaccine: placebo control) using centralized 
randomization, with a total of approximately -200 study vaccine recipients and 50 placebo 
control recipients. Treatments will be stratified as described below. 
 
5.4 
Stratification 
To satisfy the requirement that each site enrolls at least one placebo subject in each cohort, 
enrollment will proceed until treatments have been randomized to at least one complete block 
of subjects (consisting of four subjects receiving treatment and one receiving placebo) at 
each site. 
 

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Treatment allocation/randomization will be stratified by the 5 cohort groups: 
        Cohort 1: Screening CD4 cell counts for adults: CD4 cells/mm3 ≥ 500 
        Cohort 2: Screening CD4 cell counts for adults: CD4 cells/mm3 >350 and < 500 
        Cohort 3: Screening CD4 cell counts for adults: CD4 cells/mm3 ≥ 200 and ≤ 350 
        Cohort 4: Screening CD4 cell counts for adolescents, age 13 to 17: CD4 cells/mm3 ≥ 
200 
        Cohort 5: Screening CD4 cell counts for adults and adolescents, age 13 to 17: CD4 
cells/mm3 ≥ 200 with 2 doses. 
 
All sites are stratified by site (two sites per cohort). 
Cohort 5 is stratified by site, and by age group (adolescent vs. adult). Once three blocks of 
five adolescents have been enrolled, with at least one block at each site, the requirement to 
enroll at least 12 adolescents in Cohort 5 will be met. 
5.5 
Concomitant Medications/Vaccinations (Allowed & Prohibited) 
Medications or vaccinations specifically prohibited in the exclusion criteria are not allowed 
during the ongoing trial.  The investigator should discuss any questions regarding this with the 
Medical Monitor.  The final decision on any supportive therapy or vaccination rests with the 
investigator and/or the subject's primary physician.   
Listed below are specific restrictions for concomitant therapy or vaccination following each 
vaccination: 
1. 
Systemic glucocorticoids (a dose ≥ 20 mg/day prednisone or equivalent) 
within one month, or any other cytotoxic or immunosuppressive drug within 
twelve months; 
2. 
Any investigational drug within twelve months; 
3. 
Any live virus concomitant vaccinations within 42 days  
4. 
Any other (non-live) concomitant vaccinations within 14 days 
5.6 
Rescue Medications & Supportive Care 
No rescue or supportive medications are specified to be used in this trial. 
5.7 
Subject Withdrawal/Discontinuation Criteria 
Subjects may withdraw from the trial at any time for any reason or the subject may be 
withdrawn from the trial at the discretion of the investigator should any untoward effect occur.  
If a subject withdraws from the trial, they will no longer receive treatment or be followed at 
scheduled protocol visits. 
A subject must be withdrawn from the trial if: 
1. The subject or legal representative (such as parent or legal representative) withdraws 
consent from the trial. 
2. The subject is lost to follow-up 

48 
 
 
CT14B_ACHIV-Ebola Protocol Version 4.0 
17 September 2019 
 
 
5.8 
Subject Replacement Strategy 
A subject who discontinues from the trial will not be replaced. 
 
5.9 
Beginning and End of the Trial 
The overall trial begins when the first subject signs the informed consent form. The subject 
participation portion of the overall trial ends when the last subject completes the last study-
related phone call or visit, discontinues from the trial or is lost to follow-up (i.e., the subject is 
unable to be contacted by the investigator). For purposes of analysis and reporting, the overall 
trial ends when the Sponsor receives the last serology assay result or subject data from the last 
study-related phone call or visit and the database has been cleaned and locked. 
5.10 Clinical Criteria for Early Trial Termination 
There are no pre-specified criteria for terminating the trial early. The clinical trial may be 
terminated early if the extent (incidence and/or severity) of emerging effects/clinical endpoints 
is such that the risk/benefit ratio to the trial population as a whole is unacceptable.  In addition, 
further recruitment in the trial or at (a) particular trial site(s) may be stopped due to insufficient 
compliance with the protocol, GCP and/or other applicable regulatory requirements, 
procedure-related problems or the number of discontinuations for administrative reasons is too 
high. 

49 
 
CT14B_ACHIV-Ebola Protocol Version 4.0 
17 September 2019 
 
 
6.0 TRIAL FLOW CHART  
(COHORTS 1- TO 4) 
Trial Period: 
Screening 
Vaccination 
Follow-up 
Visit Number/Title: 
Screening 
1 
 
2 
3 
 
4 
 
5 
6 
 
7 
 
 
8 
Day:  
 
-30 to 0 
0 
3 
7 
14 
28 
42 
180 
 
365 
Scheduling Window (Days): 
NA 
NA 
±1 
±1 
±3 
±3 
±7 
±14 
±28 
Administrative Procedures 
 
 
 
 
 
 
 
 
 
Informed Consent 
x 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
x 
x 
 
 
 
 
 
 
 
Subject Identification Card 
x 
x 
 
 
 
 
 
 
 
Medical History 
x 
x 
 
 
 
 
 
 
 
Concomitant Medication Review 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Randomisation/Vaccine Administration 
 
x 
 
 
 
 
 
 
 
Clinical Procedures/Assessments 
 
 
 
 
 
 
 
 
 
Full Physical Examination 
x 
 
 
 
 
 
 
 
 
Height 
x 
 
 
 
 
 
 
 
 
Weight 
x 
 
 
 
 
 
 
 
 
Vital Signs (heart rate, blood pressure, 
respiratory rate, oral/tympanic/axillary 
temperature) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Post vaccination Monitoring for Hypersensitivity 
Reactions (30 Minutes) 
 
x 
 
 
 
 
 
 
 
Non-Serious Adverse Events Monitoring 
 
x 
x 
x 
x 
x 
x 
 
 
Serious Adverse Events Monitoring 
x 
x 
x 
x 
x 
x 
x 
x 
x 

50 
 
CT14B_ACHIV-Ebola Protocol Version 4.0 
17 September 2019 
 
 
Trial Period: 
Screening 
Vaccination 
Follow-up 
Visit Number/Title: 
Screening 
1 
 
2 
3 
 
4 
 
5 
6 
 
7 
 
 
8 
Day:  
 
-30 to 0 
0 
3 
7 
14 
28 
42 
180 
 
365 
Scheduling Window (Days): 
NA 
NA 
±1 
±1 
±3 
±3 
±7 
±14 
±28 
Distribute Patient Memory Aid and Review 
Procedures with Subject 
 
x 
 
 
 
 
 
 
 
Review Arthralgia/Arthritis, Rash and/or Vesicular 
Lesion Reporting Requirements with Subjecta 
x 
x 
x 
x 
x 
x 
x 
 
 
Review Memory Aid with Subject 
 
 
x 
x 
x 
x 
x 
 
 
Collect Memory Aid from Subject 
 
 
 
 
 
 
x 
 
 
Laboratory Procedures/Assessments 
 
 
 
 
 
 
 
 
 
Hematology (~4mls) 
x 
x 
x 
x 
x 
x 
x 
 
 
Urinalysis  
x 
 
 
 
 
 
 
 
 
Chemistry (~8mls) 
x 
x 
x 
x 
x 
x 
x 
 
 
Urine Pregnancy Test (if applicable based on 
subject’s age/gender) 
x 
x 
 
 
 
 
 
 
 
HIV serology (if not previously documented) 
(~8mls) 
x 
 
 
 
 
 
 
 
 
HBsAg  (~8mls) 
x 
 
 
 
 
 
 
 
 
Hepatitis B & C serology (combined with 
HBsAg) 
x 
 
 
 
 
 
 
 
 
ZEBOV-specific Serum Antibodies (~20mls-
combined with ZEBOV-specific Neutralizing 
antibodies) 
 
xb 
 
 
 
x 
 
x 
x 
ZEBOV-specific Neutralizing antibodies (see 
volume above) 
 
xb 
 
 
 
x 
 
x 
x 

51 
 
CT14B_ACHIV-Ebola Protocol Version 4.0 
17 September 2019 
 
 
Trial Period: 
Screening 
Vaccination 
Follow-up 
Visit Number/Title: 
Screening 
1 
 
2 
3 
 
4 
 
5 
6 
 
7 
 
 
8 
Day:  
 
-30 to 0 
0 
3 
7 
14 
28 
42 
180 
 
365 
Scheduling Window (Days): 
NA 
NA 
±1 
±1 
±3 
±3 
±7 
±14 
±28 
VSV (Blood, Urine and Saliva Sample) (~5mls 
blood) 
 
 
x 
x 
x 
x 
x 
 
 
HIV viral load (~8mls) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
CD4/CD8 T Lymphocytes count (~4mls) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
HIV RNA (reservoirs) (~20 mls combined with 
HIV DNA and  HIV TILDA below) 
 
x 
 
 
 
x 
 
x 
x 
HIV DNA (reservoirs) (see volume above) 
 
x 
 
 
 
x 
 
x 
x 
HIV TILDA (reservoirs) (see volume above) 
 
x 
 
 
 
x 
 
x 
x 
*Biobank samples-optional (~35mls) 
 
xb 
 
 
 
x 
 
x 
x 
Total Blood volumes  
(*including optional Biobank sample)  
~ 40mls 
 
~64mls 
(*~89mls) 
~29mls 
 
~29mls 
 
~29mls 
 
~69mls 
(*~94mls) 
~29mls 
 
~52mls 
(*~87mls) 
~52mls 
(*~87mls) 
a. 
Specimens should be obtained for rVSV detection by PCR in through 42 days from skin vesicles, joint fluid, or skin 
biopsies  
b. 
Specimens should be obtained before vaccination 

52 
 
 
CT14B_ACHIV-Ebola Protocol Version 4.0                                           
17 September 2019 
 
 
(COHORT 5) 
Trial Period: 
Screening 
Vaccination 
Follow-up 
Visit Number/Title: 
Screening 
 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11  
12 
13 
14 
Day: 
 
-30 to 0 
0 
3 
7 
14 
28 
42 
56 
3 
day
s 
pos
t 
dos
e 2 
7 
day
s 
pos
t 
dos
e 2 
14 
day
s 
pos
t 
dos
e 2 
28 
day
s 
pos
t 
dos
e 2 
42 
day
s 
pos
t 
dos
e 2 
180 
 
365 
 
Scheduling Window (Days): 
NA 
NA 
±1 
±1 
±3 
±3 
±7 
±3 
±1 
±1 
±3 
±3 
±7 
±14 
±28 
Administrative Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed Consent 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
x 
x 
 
 
 
 
 
x 
 
 
 
 
 
 
 
Subject Identification Card 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medication Review 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Randomisation/ 
 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vaccine Administration 
 
x 
 
 
 
 
 
x 
 
 
 
 
 
 
 
Clinical Procedures/Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Full Physical Examination 
x 
 
 
c. 
 
 
 
 
 
 
 
 
 
 
 

53 
 
 
CT14B_ACHIV-Ebola Protocol Version 4.0                                           
17 September 2019 
 
 
Trial Period: 
Screening 
Vaccination 
Follow-up 
Visit Number/Title: 
Screening 
 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11  
12 
13 
14 
Day: 
 
-30 to 0 
0 
3 
7 
14 
28 
42 
56 
3 
day
s 
pos
t 
dos
e 2 
7 
day
s 
pos
t 
dos
e 2 
14 
day
s 
pos
t 
dos
e 2 
28 
day
s 
pos
t 
dos
e 2 
42 
day
s 
pos
t 
dos
e 2 
180 
 
365 
 
Scheduling Window (Days): 
NA 
NA 
±1 
±1 
±3 
±3 
±7 
±3 
±1 
±1 
±3 
±3 
±7 
±14 
±28 
Height 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital Signs (heart rate, blood pressure, respiratory 
rate, oral/tympanic/axillary temperature) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Post vaccination Monitoring for Hypersensitivity 
Reactions (30 Minutes) 
 
x 
 
 
 
 
 
x 
 
 
 
 
 
 
 
Non-Serious Adverse Events Monitoring 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
Serious Adverse Events Monitoring 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Distribute Patient Memory Aid and Review 
Procedures with Subject 
 
x 
 
 
 
 
 
x 
 
 
 
 
 
 
 
Review Arthralgia/Arthritis, Rash and/or Vesicular 
Lesion Reporting Requirements with Subjecta 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
Review Memory Aid with Subject 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 

54 
 
 
CT14B_ACHIV-Ebola Protocol Version 4.0                                           
17 September 2019 
 
 
Trial Period: 
Screening 
Vaccination 
Follow-up 
Visit Number/Title: 
Screening 
 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11  
12 
13 
14 
Day: 
 
-30 to 0 
0 
3 
7 
14 
28 
42 
56 
3 
day
s 
pos
t 
dos
e 2 
7 
day
s 
pos
t 
dos
e 2 
14 
day
s 
pos
t 
dos
e 2 
28 
day
s 
pos
t 
dos
e 2 
42 
day
s 
pos
t 
dos
e 2 
180 
 
365 
 
Scheduling Window (Days): 
NA 
NA 
±1 
±1 
±3 
±3 
±7 
±3 
±1 
±1 
±3 
±3 
±7 
±14 
±28 
Collect Memory Aid from Subject 
 
 
 
 
 
 
x 
 
 
 
 
 
x 
 
 
Laboratory Procedures/Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology (~4mls) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
Urinalysis  
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chemistry (~8mls) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
Urine Pregnancy Test (if applicable based on 
subject’s age/gender) 
x 
x 
 
 
 
 
 
x 
 
 
 
 
 
 
 
HIV serology (if not previously documented) 
(~8mls) 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HBsAg  (~8mls) 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis B & C serology (combined with HBsAg) 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

55 
 
 
CT14B_ACHIV-Ebola Protocol Version 4.0                                           
17 September 2019 
 
 
Trial Period: 
Screening 
Vaccination 
Follow-up 
Visit Number/Title: 
Screening 
 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11  
12 
13 
14 
Day: 
 
-30 to 0 
0 
3 
7 
14 
28 
42 
56 
3 
day
s 
pos
t 
dos
e 2 
7 
day
s 
pos
t 
dos
e 2 
14 
day
s 
pos
t 
dos
e 2 
28 
day
s 
pos
t 
dos
e 2 
42 
day
s 
pos
t 
dos
e 2 
180 
 
365 
 
Scheduling Window (Days): 
NA 
NA 
±1 
±1 
±3 
±3 
±7 
±3 
±1 
±1 
±3 
±3 
±7 
±14 
±28 
ZEBOV-specific Serum Antibodies (~20mls-
combined with ZEBOV-specific Neutralizing 
antibodies) 
 
xb 
 
 
 
x 
 
xb 
 
 
 
x 
 
x 
x 
ZEBOV-specific Neutralizing antibodies (see 
volume above) 
 
xb 
 
 
 
x 
 
xb 
 
 
 
x 
 
x 
x 
VSV (Blood, Urine and Saliva Sample) (~5mls 
blood) 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
HIV viral load (~8mls) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
CD4/CD8 T Lymphocytes count (~4mls) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Total Blood volumes  
 
~ 40mls 
 
~44mls 
 
~29
mls 
 
~29
mls 
 
~29
mls 
 
~49
mls 
 
~29
mls 
 
~49
mls 
 
 
~29
mls 
 
~29
mls 
 
~29
mls 
 
~49
mls 
 
~29
mls 
 
~32
mls 
 
~32
mls 
 
a Specimens should be obtained for rVSV detection by PCR in through 42 days from skin vesicles, joint fluid, or skin biopsies 
b Specimens should be obtained before vaccination 

56 
 
 
CT14B_ACHIV-Ebola Protocol Version 4.0                                           
17 September 2019 
 
 
 
7.0 TRIAL PROCEDURES 
7.1 
Trial Procedures 
The Trial Flow Chart - Section 6.0 summarizes the trial procedures to be performed at each 
visit.  Individual trial procedures are described in detail below.  It may be necessary to perform 
these procedures at unscheduled time points if deemed clinically necessary by the investigator. 
Furthermore, additional evaluations/testing may be deemed necessary by the investigator and 
or the Sponsor for reasons related to subject safety. In some cases, such evaluation/testing may 
be potentially sensitive in nature (e.g., HIV, Hepatitis C, etc.), and thus local regulations may 
require that additional informed consent be obtained from the subject.  In these cases, such 
evaluations/testing will be performed in accordance with those regulations. 
7.1.1 Administrative Procedures 
7.1.1.1 Informed Consent 
The investigator or qualified designee must obtain documented consent from each potential 
subject or each subject’s legally acceptable representative prior to participating in a clinical 
trial. If there are changes to the subject’s status during the trial (e.g., health or age of majority 
requirements), the investigator or qualified designee must ensure the appropriate consent is in 
place.  
7.1.1.1.1 General Informed Consent 
Consent must be documented by the subject’s dated signature or by the subject’s legally 
acceptable representative’s dated signature on a consent form along with the dated signature 
of the person conducting the consent discussion.  
A copy of the signed and dated consent form should be given to the subject before participation 
in the trial. 
The initial informed consent form, any subsequent revised written informed consent form and 
any written information provided to the subject must receive the IRB/ERC’s 
approval/favorable opinion in advance of use.  The subject or his/her legally acceptable 
representative should be informed in a timely manner if new information becomes available 
that may be relevant to the subject’s willingness to continue participation in the trial.  The 
communication of this information will be provided and documented via a revised consent 
form or addendum to the original consent form that captures the subject’s dated signature or 
by the subject’s legally acceptable representative’s dated signature. 
Specifics about a trial and the trial population will be added to the consent form template at 
the protocol level.   
The informed consent will adhere to IRB/ERC requirements, applicable laws and regulations, 
and Sponsor requirements. 

57 
 
 
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7.1.1.2 Inclusion/Exclusion Criteria 
All inclusion and exclusion criteria will be reviewed by the investigator or qualified designee 
to ensure that the subject qualifies for the trial. 
7.1.1.3 Subject Identification Card 
All subjects will be given a Subject Identification Card identifying them as participants in a 
research trial. The card will contain trial site contact information (including direct telephone 
numbers) to be utilized in the event of an emergency. The investigator or qualified designee 
will provide the subject with a Subject Identification Card immediately after the subject 
provides written informed consent. At the time of treatment allocation/randomization, site 
personnel will add the treatment/randomization number to the Subject Identification Card. 
The subject identification card also contains contact information for the emergency unblinding 
so that a health care provider can obtain information about trial medication/vaccination in 
emergency situations where the investigator is not available. 
7.1.1.4 Medical History 
A medical history will be obtained by the investigator or qualified designee.  Record any pre-
existing conditions or signs and/or symptoms present in a participant prior to the first study 
injection. 
7.1.1.5 Prior and Concomitant Medications Review 
7.1.1.5.1 Prior Medications 
The investigator or qualified designee will review prior medication use, including any 
protocol-specified washout requirement, and record prior medication taken by the subject 
within 6 months before dose of trial vaccination. 
7.1.1.5.2 Concomitant Medications 
The investigator or qualified designee will record medication, if any, taken by the subject 
during the trial. 
7.1.1.6 Assignment of Screening Number 
All consented subjects will be given a unique screening number that will be used to identify 
the subject for all procedures that occur prior to randomization or treatment allocation.  Each 
subject will be assigned only one screening number.  Screening numbers must not be re-used 
for different subjects. 
Any subject who is screened multiple times will retain the original screening number assigned 
at the initial screening visit. 
Specific details on the screening visit requirements (screening/rescreening) are provided in 
Section 7.1.5.1.   

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CT14B_ACHIV-Ebola Protocol Version 4.0                                           
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7.1.1.7 Assignment of Treatment/Randomization Number 
All eligible subjects will be randomly allocated and will receive a treatment/randomization 
number.  The treatment/randomization number identifies the subject for all procedures 
occurring after treatment allocation/randomization.  Once a treatment/randomization number 
is assigned to a subject, it can never be re-assigned to another subject.  
A single subject cannot be assigned more than 1 treatment/randomization number. 
7.1.1.8 Trial Compliance  
Interruptions from the protocol specified vaccination plan require consultation between the 
investigator and the Sponsor and written documentation of the collaborative decision on 
subject management. 
Administration of trial vaccination will be witnessed by the investigator and/or trial staff. 
7.1.2 Clinical Procedures/Assessments 
Cohorts 1 to 5: 
At the screening visit after the Informed consent will be signed a full medical evaluation will 
be performed, including physical examination, vital signs (heart rate, blood pressure, 
oral/tympanic/axillary temperature, respiratory rate), height and weight.  
Cohorts 1 to 4:  
At visit 1 (Randomization /vaccination), the inclusion and exclusion criteria will be reviewed 
by the investigator or qualified designee to ensure that the subject still qualifies for the trial. 
Vital Signs will be taken (including heart rate, blood pressure, oral/tympanic/axillary 
temperature, respiratory rate). Participant will be coming to the center at day 3 (visit 2), day 7 
(visit 3), day 14 (visit 4), day 28 (visit 5), day 42 (visit 6), day180 (visit 7) and day 365 (visit 
8).  Vital Signs will be taken (including heart rate, blood pressure, oral/tympanic/axillary 
temperature, respiratory rate) at all visits.  Non-Serious Adverse Events including solicited and 
unsolicited adverse events will be monitored at every visit through Day 42.  Serious Adverse 
Events will be monitored at every visit through Day 365.  
Cohort 5:  
At visit 1 (Randomization /vaccination), the inclusion and exclusion criteria will be reviewed 
by the investigator or qualified designee to ensure that the subject still qualifies for the trial. 
At visit 1 (first dose of vaccine or placebo) and visit 7 (second dose of matching vaccine or 
placebo), vital signs will be taken (including heart rate, blood pressure, oral/tympanic/axillary 
temperature, respiratory rate) 
Participant will be coming to the study site at Screening (day -30 to 0), day 0 (visit 1), day 3 
(visit 2), day 7 (visit 3), day 14 (visit 4), day 28 (visit 5), day 42 (visit 6), day 56 (visit 7), 3 
days post dose 2 (visit 8), 7 days post dose 2 (visit 9), 14 days post dose 2 (visit 10), 28 days 
post dose 2 (visit 11), 42 days post dose 2 (visit 12), day180 (visit 13) and day 365 (visit 14).  
Vital Signs will be taken (including heart rate, blood pressure, oral/tympanic/axillary 

59 
 
 
CT14B_ACHIV-Ebola Protocol Version 4.0                                           
17 September 2019 
 
 
temperature, respiratory rate) at all visits.  Non-Serious Adverse Events including solicited and 
unsolicited adverse events will be monitored at every visit after first dose of vaccine or placebo 
through Day 42.  Non-Serious Adverse Events including solicited and unsolicited adverse 
events will be monitored at every visit after second dose of matching vaccine or placebo 
through Day 42. Serious Adverse Events will be monitored at every visit through Day 365.  
 
7.1.3 Laboratory Procedures/Assessments 
Details regarding specific laboratory procedures/assessments to be performed in this trial are 
provided below. The total amount of blood to be drawn/collected over the course of the trial 
including approximate blood volumes drawn/collected by visit and by sample type per subject 
will not exceed 10.5mls/kg or 550mls, whichever is less,   in an 8 week period as per NIH 
recommendations (https://irb.research.chop.edu/sites/default/files/documents/g_ nih_blood 
draws. pdf). In addition to anti-Ebola immune assessments blood samples, optional  blood 
samples will be drawn at visits 1, 5, 7, & 8 (cohorts 1-4) if subjects sign a separate consent 
form.  These samples will be conserved in a biobank for future research studies.  These studies 
will serve to add in depth knowledge on the Ebola-specific and HIV-specific immune 
responses as it relates to cytotoxic T cells activation, innate immunity and virological studies.  
All study samples will be managed by the Canadian Center for Vaccinology (CCfV), Halifax, 
NS, under the custody of Dalhousie University on behalf of the Canadian Immunization 
Research Network (CIRN).  Testing of samples will be conducted by Focus Diagnostics 
Clinical Trials, a Q2 Solutions Quintiles Quest Joint Venture Company, located at 33608 
Ortega Highway, San Juan Capistrano, CA 92675 and at the lab of Dr. Cecile Tremblay, the 
Laboratory of Retrovirology, CRCHUM at 900 St- Denis street Tour Viger, Montreal.   
7.1.3.1 Laboratory Evaluations (Hematology, Chemistry and Urinalysis) 
Laboratory tests for hematology, chemistry and urinalysis are specified in Table 3. 
Table 3: Laboratory Tests 
Hematology 
Chemistry 
Urinalysis 
Other 
 Hemoglobin 
Blood Urea Nitrogen 
Blood 
Urine pregnancy test 
  WBC (total 
and differential) 
Creatinine 
Glucose 
Hepatitis B and  C 
Serology 
 Platelets 
Alanine aminotransferase 
(ALT) 
Protein 
HbsAg 
RBC 
Aspartate aminotransferase 
(AST) 
 
 HIV ELISA 
Hematocrit 
Glucose 
Microscopic exam, 
if abnormal results 
are noted 
 HIV viral load 

60 
 
 
CT14B_ACHIV-Ebola Protocol Version 4.0                                           
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Hematology 
Chemistry 
Urinalysis 
Other 
MCV (mean 
corpuscular 
volume) 
 
 
CD4/CD8+ 
Lymphocytes 
MCH (mean 
corpuscular 
hemoglobin) 
 
 
Serum antibodies 
against ZEBROV  and 
Neutralizing antibodies 
(GMT) (sent to Focus 
Laboratory)  
MCHC (mean 
corpuscular 
hemoglobin 
concentration) 
 
 
VSV-urine, saliva, 
plasma and any AE 
samples (sent to Focus 
Laboratory) 
RDW (RBC 
Distribution 
Width) 
 
 
HIV RNA, HIV DNA, 
HIV TILDA and 
optional Biobank 
Samples-sent to 
CRCHUM laboratory 
(Cohort 1 – 4 only)  
 
 
 
C-Reactive Protein 
 
7.1.4 Other Procedures 
7.1.4.1 HIV Viral Load 
HIV viral load will be monitored throughout the study.  Standard of care treatment appropriate 
for the viral load, clinical presentation, and other clinical laboratory evaluation will be 
provided. 
7.1.4.2 Withdrawal/Discontinuation 
Subjects who discontinue/withdraw from completion of all study related procedures should be 
encouraged to continue to be followed for safety assessment at all remaining study visits. 
7.1.4.3 Blinding/Unblinding 
This is a double blind trial; unblinding will be performed after the database is locked.   
A participant may be unblinded during the course of the study if the PI deems that, for health 
purposes, the blind must be broken. Only in the case of an emergency, when knowledge of 
whether the participant has received the investigational product is essential for the clinical 
management or welfare of the participant, the investigator may authorize the unblinding of a 
participant’s treatment assignment. If time permits, the investigator or qualified study staff 

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designee is encouraged to contact the Sponsor coordinating PI, Dr. Joanne Langley, prior to 
breaking the blind. 
 
7.1.4.4 Calibration of Critical Equipment 
The investigator or qualified designee has the responsibility to ensure that any critical device 
or instrument used for a clinical evaluation/test during a clinical trial that provides important 
information about inclusion/exclusion criteria and/or safety or efficacy parameters shall be 
suitably calibrated and maintained to ensure that the data obtained is reliable and/or 
reproducible.  Documentation of equipment calibration must be retained as source 
documentation at the trial site. 
7.1.5 Visit Requirements 
Visit requirements are outlined in Section 6.0 - Trial Flow Chart.   Specific procedure-related 
details are provided above in Section 7.1 - Trial Procedures. 
7.1.5.1 Screening 
Approximately 30 days prior to treatment allocation/randomization, potential subjects will be 
evaluated to determine that they fulfill the entry requirements as set forth in Section 5.1. To 
exclude transient laboratory abnormalities, the investigator may repeat a test once during the 
screening period (ie a maximum of two tests), and if the repeat test is normal, subject may be 
enrolled. If the screening period for a particular study cohort has elapsed, a participant who 
was not eligible for an earlier cohort may be screened for eligibility for a later cohort. 
7.1.5.2 Vaccination Visit 
One dose of study vaccine will be administered at Visit 1 to participants in Cohort 1-4.  Two 
doses of study vaccine will be administered to Cohort 5 participants: first at visit 1 and second 
dose at visit 7. 
7.2 
Assessing and Recording Adverse Events 
An adverse event is defined as any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and which does not necessarily 
have to have a causal relationship with this treatment. An adverse event can therefore be any 
unfavorable and unintended sign (including an abnormal laboratory finding, for example), 
symptom, or disease temporally associated with the use of a medicinal product or protocol-
specified procedure, whether or not considered related to the medicinal product or protocol-
specified procedure.  Any worsening of a preexisting condition that is temporally associated 
with the use of the Study product, is also an adverse event. 
Changes resulting from normal growth and development that do not vary significantly in 
frequency or severity from expected levels are not to be considered adverse events.  Examples 
of this may include, but are not limited to, onset of menses or menopause occurring at a 
physiologically appropriate time. 

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Study product includes any pharmaceutical product, biological product, device, diagnostic 
agent or protocol-specified procedure, whether investigational (including active control 
medication) or marketed (including normal saline placebo), provided by or distributed by the 
Sponsor for human use in this study. 
Adverse events may occur during clinical trials, or as prescribed in clinical practice, from 
overdose (whether accidental or intentional), from abuse and from withdrawal. 
All adverse events that occur after the consent form is signed but before 
allocation/randomization must be reported by the investigator if they cause the subject to be 
excluded from the trial, or are the result of a protocol-specified intervention, including but not 
limited to study procedures. From the time of allocation/randomization through 42 days 
following each vaccination, all adverse events must be reported by the investigator. Such 
events will be recorded at each examination on the Adverse Event case report 
forms/worksheets. The reporting timeframe for adverse events meeting any serious criteria is 
described in section 7.2.3.1. The investigator will make every attempt to follow all subjects 
with non-serious adverse events for outcome. 
Electronic reporting procedures can be found in the Electronic Data Capture (EDC) data entry 
guidelines. Paper reporting procedures can be found in the Investigator Trial File Binder (or 
equivalent). 
Pre-existing conditions or signs and/or symptoms present in a participant prior to the first study 
injection are not considered to be adverse events.  These events will be recorded in the 
participants’ medical history. 
 
7.2.1 Definition of an Overdose and Reporting Overdose to the Sponsor 
In this trial, an overdose is defined as greater than one dose of the investigational V920 
vaccine/placebo. 
 
7.2.2 Events Specific to Post Vaccination 
Study subjects who develop joint pain, swelling or stiffness (arthralgia/arthritis) symptoms, a 
rash and/or small vesicles from day of vaccination until day 42 following each vaccination 
are instructed to notify the study site.  They will be assessed by the investigator, and it will be 
determined if they require any additional samples collected, and/or a referral for specialist 
care, if needed. Specific instructions are provided to the sites in a guidance document for the 
assessment and work-up of these specific post vaccination events. 
7.2.3 Reporting of Pregnancy and Lactation to the Sponsor  
Although pregnancy and lactation are not considered adverse events, it is the responsibility of 
investigators or their designees to report any pregnancy or lactation in a subject (spontaneously 
reported to them) that occurs during the trial. 

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Pregnancies and lactations that occur after the consent form is signed but before treatment 
allocation/randomization must be reported by the investigator if they cause the subject to be 
excluded from the trial, or are the result of a protocol-specified intervention, including but not 
limited to washout or discontinuation of usual therapy, diet, placebo treatment or a procedure.  
Pregnancies and lactations that occur from the time of treatment allocation/randomization 
through 42 days following any vaccination must be reported by the investigator.  All reported 
pregnancies must be followed to the completion/termination of the pregnancy. Pregnancy 
outcomes of spontaneous abortion, missed abortion, benign hydatidiform mole, blighted ovum, 
fetal death, intrauterine death, miscarriage and stillbirth must be reported as serious events 
(Important Medical Events). If the pregnancy continues to term, the outcome (health of infant) 
must also be reported. 
Such events must be reported within 24 hours to the Sponsor either by electronic media or 
paper. Electronic reporting procedures can be found in the EDC data entry guidelines. Paper 
reporting procedures can be found in the Investigator Trial File Binder (or equivalent). 
7.2.4 Immediate Reporting of Adverse Events to the Sponsor 
7.2.4.1 Serious Adverse Events 
A serious adverse event is any adverse event occurring at any dose or during any use of Study 
product that: 
● results in death; 
● is life threatening; 
● results in persistent or significant disability/incapacity; 
● results in or prolongs an existing inpatient hospitalization; 
● is a congenital anomaly/birth defect; 
● is another important medical event.  
Note: In addition to the above criteria, adverse events meeting either of the below criteria, 
although not serious per ICH definition, are reportable to the Sponsor in the same timeframe 
as SAEs to meet certain local requirements. Therefore, these events are considered serious by 
the Sponsor for collection purposes. 
● Is a cancer; 
● Is associated with an overdose. 
Refer to Table 4 for additional details regarding each of the above criteria.   
For the time period beginning when the consent form is signed until treatment 
allocation/randomization, any serious adverse event, or follow up to a serious adverse event, 
including death due to any cause, that occurs to any subject must be reported within 24 hours 
to the Sponsor if it causes the subject to be excluded from the trial, or is the result of a protocol-
specified intervention or procedure. 
For the time period beginning at treatment allocation/randomization through 365 days 
following first vaccination, any serious adverse event, or follow up to a serious adverse event, 
including death due to any cause, whether or not related to the Study product, must be reported 
within 24 hours to the Sponsor either by electronic media or paper. Electronic reporting 

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procedures can be found in the EDC data entry guidelines. Paper reporting procedures can be 
found in the Investigator Trial File Binder (or equivalent). 
Additionally, any serious adverse event brought to the attention of an investigator who is a 
qualified physician at any time outside of the time period specified in the previous paragraph 
also must be reported immediately to the Sponsor if the event is either: 
1.  A death that occurs prior to the subject completing the trial, but outside the time period 
specified in the previous paragraph. 
or 
2.  A serious adverse event that is considered by an investigator who is a qualified physician 
to be vaccine related. 
All subjects with serious adverse events must be followed up for outcome. 
7.2.4.2 Events of Clinical Interest 
Selected non-serious and serious adverse events are also known as Events of Clinical Interest 
(ECI) and must be reported to the Sponsor. 
For the time period beginning when the consent form is signed until treatment 
allocation/randomization, any ECI, or follow up to an ECI, that occurs to any subject must be 
reported within 24 hours to the Sponsor if it causes the subject to be excluded from the trial, 
or is the result of a protocol-specified intervention, including but not limited to washout or 
discontinuation of usual therapy, diet, placebo treatment or a procedure. 
For the time period beginning at treatment allocation/randomization through 42 days following 
vaccination, any ECI, or follow up to an ECI, whether or not related to the Study product, must 
be reported within 24 hours to the Sponsor, either by electronic media or paper.  Electronic 
reporting procedures can be found in the EDC data entry guidelines.  Paper reporting 
procedures can be found in the Investigator Trial File Binder (or equivalent). 
Events of clinical interest for this trial include: 
1. 
An overdose of Study product, as defined in Section 7.2.1 - Definition 
of an Overdose for This Protocol and Reporting of Overdose to the 
Sponsor, that is not associated with clinical symptoms or abnormal 
laboratory results. 
 
7.2.5 Evaluating Adverse Events 
An investigator who is a qualified physician will evaluate all adverse events with respect to 
the elements outlined in Table 4. The investigator’s assessment of causality is required for 
each adverse event.  Refer to Table 4 for instructions in evaluating adverse events. 

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Table4: Evaluating Adverse Events 
 
Maximum 
Mild 
awareness of sign or symptom, but easily tolerated (for pediatric trials, awareness of symptom, but easily tolerated) 
Intensity 
Moderate 
discomfort enough to cause interference with usual activity (for pediatric trials, definitely acting like something is wrong) 
 
Severe 
incapacitating with inability to work or do usual activity (for pediatric trials, extremely distressed or unable to do usual activities) Injection 
site redness or swelling from the day of vaccination (D0) through Day 14 post-vaccination will be evaluated by maximum size. 
Seriousness 
A serious adverse event (AE) is any adverse event occurring at any dose that: 
 
†Results in death; or 
 
†Is life threatening; or places the subject, in the view of the investigator, at immediate risk of death from the event as it occurred [Note: This does not include an adverse 
event that, had it occurred in a more severe form, might have caused death.]; or 
 
†Results in a persistent or significant disability/incapacity (substantial disruption of one’s ability to conduct normal life functions); or 
 
†Results in or prolongs an existing inpatient hospitalization (hospitalization is defined as an inpatient admission, regardless of length of stay, even if the hospitalization 
is a precautionary measure for continued observation.   (Note: Hospitalization for an elective procedure to treat a pre-existing condition that has not worsened is not a 
serious adverse event.  A pre-existing condition is a clinical condition that is diagnosed prior to the use of study product and is documented in the patient’s medical 
history.); or 
 
†Is a congenital anomaly/birth defect  (in offspring of subject taking the product regardless of time to diagnosis); or 
 
Is a cancer (although not serious per ICH definition, is reportable to the Sponsor within 24 hours to meet certain local requirements; or 
 
Is associated with an overdose (whether accidental or intentional).  Any adverse event associated with an overdose is considered a serious adverse event for collection 
purposes. An overdose that is not associated with an adverse event is considered a non-serious event of clinical interest and must be reported within 24 hours. 
 
Other important medical events that may not result in death, not be life threatening, or not require hospitalization may be considered a serious adverse event when, 
based upon appropriate medical judgment, the event may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed 
previously (designated above by a †). 
Duration 
Record the start and stop dates of the adverse event.  If less than 1 day, indicate the appropriate length of time and units 
Action taken  
Did the adverse event cause the test vaccine to be discontinued? 
Relationship 
to test vaccine  
Did the test vaccine cause the adverse event?   The determination of the likelihood that the test vaccine caused the adverse event will be provided by an investigator 
who is a qualified physician.  The investigator’s signed/dated initials on the source document or worksheet that supports the causality noted on the AE form, ensures 
that a medically qualified assessment of causality was done.  This initialed document must be retained for the required regulatory time frame.  The criteria below are 
intended as reference guidelines to assist the investigator in assessing the likelihood of a relationship between the test vaccine and the adverse event based upon the 
available information.   
The following components are to be used to assess the relationship between the test vaccine and the AE; the greater the correlation with the components and their 
respective elements (in number and/or intensity), the more likely the test vaccine caused the adverse event: 
 
Exposure 
Is there evidence that the subject was actually exposed to the test vaccine such as:  reliable history, acceptable compliance assessment (e.g., 
diary), seroconversion or identification of vaccine virus in bodily specimen? 
 
Time Course 
Did the AE follow in a reasonable temporal sequence from administration of the test vaccine?  
Is the time of onset of the AE compatible with a vaccine-induced effect? 
 
Likely Cause 
Is the AE not reasonably explained by another etiology such as underlying disease, other drug(s)/vaccine(s), or other host or environmental 
factors 

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Relationship 
The following components are to be used to assess the relationship between the test vaccine and the AE:  (continued) 
to test vaccine  
Dechallenge 
(not applicable for vaccines) 
(continued)  
Rechallenge 
Was the subject reexposed to the test vaccine in this trial? 
      If yes, did the AE recur or worsen? 
          If yes, this is a positive rechallenge.    If no, this is a negative rechallenge. 
(Note:  This criterion is not applicable if:  (1) the initial AE resulted in death or permanent disability, or (2) the trial is a single-dose vaccine 
trial.) 
NOTE:  IF A RECHALLENGE IS PLANNED FOR AN ADVERSE EVENT WHICH WAS SERIOUS AND WHICH MAY HAVE BEEN 
CAUSED BY THE TEST VACCINE, OR IF REEXPOSURE TO THE TEST VACCINE POSES ADDITIONAL POTENTIAL 
SIGNIFICANT RISK TO THE SUBJECT, THEN THE RECHALLENGE MUST BE APPROVED IN ADVANCE BY THE SPONSOR 
CLINICAL DIRECTOR AND THE INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE. 
 
Consistency with Trial 
Vaccine Profile 
Is the clinical/pathological presentation of the AE consistent with previous knowledge regarding the test vaccine or vaccine class 
pharmacology or toxicology? 
The assessment of relationship will be reported on the case report forms /worksheets by an investigator who is a qualified physician according to his/her best clinical judgment, including 
consideration of the above elements.   
Record one of the following: 
Use the following criteria as guidance (not all criteria must be present to be indicative of a vaccine relationship). 
Yes, there is a reasonable possibility of 
vaccine relationship. 
There is evidence of exposure to the test vaccine.  The temporal sequence of the AE onset relative to the administration of the test vaccine 
is reasonable.  The AE is more likely explained by the test vaccine than by another cause. 
 
No, there is not a reasonable possibility of 
vaccine relationship 
Subject did not receive the test vaccine OR temporal sequence of the AE onset relative to administration of the test vaccine is not reasonable 
OR the AE is more likely explained by another cause than the Study product.  (Also entered for a subject with overdose without an 
associated AE.) 
 

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7.2.6 Sponsor Responsibility for Reporting Adverse Events 
All Serious Adverse Events will be reported to regulatory authorities, IRB/IECs and 
investigators in Guidelines for Good Clinical Practice.  
7.3 
TRIAL GOVERNANCE AND OVERSIGHT 
7.3.1 Stakeholder Group 
This trial was developed in collaboration with a group of stakeholders comprised of Dalhousie 
University, CIRN, IDRC, Merck and the trial P.I. 
7.3.2 Trial Steering Committee 
This trial will be conducted in consultation with a Trial Steering Committee.  The Trial Steering 
Committee comprises: 
• Sponsor Representatives 
• Investigators participating in the trial  
• Manufacturer Representative  
The Trial Steering Committee will provide guidance on the operational aspects of the trial, and 
will receive and implement recommendations from the DSMB.  
7.3.3 Data Safety and Monitoring Board 
To supplement the routine trial monitoring outlined in this protocol, an external DSMB will 
monitor the interim data from this trial.  The voting members of the committee are external to 
the Sponsor.  The members of the DSMB must not be involved with the trial in any other way 
(e.g., they cannot be trial investigators) and must have no competing interests that could affect 
their roles with respect to the trial.  
The DSMB will make recommendations to the Trial Steering Committee regarding steps to 
ensure both subject safety and the continued ethical integrity of the trial.  Also, the DSMB will 
review interim safety results, consider the overall risk and benefit to trial participants and 
recommend to the Trial Steering Committee if the trial should continue in accordance with the 
protocol. Specific stopping rules can be found in Section 14. Appendix 3. 
Specific details regarding composition, responsibilities, and governance, including the roles 
and responsibilities of the various members and the sponsor protocol team; meeting 
facilitation; the trial governance structure; and requirements for and proper documentation of 
DSMB reports, minutes, and recommendations will be described in a separate charter that is 
reviewed and approved by the DSMB.  The DSMB will monitor the trial at an appropriate 
frequency, as described in the detailed DSMB charter.  The DSMB will also make 
recommendations to the TSC regarding steps to ensure both subject safety and the continued 
ethical integrity of the trial. 
 A DSMB recommendation will be communicated to the Sponsor as agreed to in the 
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8.0 STATISTICAL ANALYSIS PLAN 
This section outlines the statistical analysis strategy and procedures for the study. If, after 
the study has begun, but prior to any final database lock, changes are made to primary and/or 
key secondary hypotheses, or the statistical methods related to those hypotheses, then the 
protocol will be amended (consistent with ICH Guideline E-9). Changes to exploratory or 
other non-confirmatory analyses made after the protocol has been finalized, but prior to final 
database lock, will be documented in a supplemental Statistical Analysis Plan (sSAP) and 
referenced in the Clinical Study Report (CSR) for the study. Post-hoc exploratory analyses 
will be clearly identified in the CSR. 
 
8.1 
Statistical Analysis Plan Summary 
Key elements of the statistical analysis plan are summarized below; the comprehensive plan is 
provided in Sections 8.2.   
Study Design Overview 
V920 (rVSVΔG-ZEBOV-GP) Ebola Virus Vaccine Candidate in HIV-
Infected Adults and Adolescents 
Treatment Assignment 
Participants in Cohort 1-4, will be randomly assigned to receive one dose 
of ≥2 x 107 pfu of the study vaccine or the placebo control in a ratio of 4 
to 1 (200:50).  Participants in Cohort 5 will be randomly assigned to 
receive one dose of ≥2 x 107 pfu of the study vaccine or the placebo control 
in a ratio of 4 to 1 (40:10) on Day 0, followed by booster vaccination at 
Day 56. 
Primary Endpoint(s) 
Safety, and ZEBOV-specific antibody responses. 
Analysis Populations 
The Per-Protocol population (PP) will serve as the primary population for 
the analysis of immunogenicity data in this study. The Per-Protocol 
population excludes subjects due to important deviations from the 
protocol that may substantially affect the results of the primary 
immunogenicity endpoint(s). For example, subjects who are seropositive 
at baseline will be excluded from the Per-Protocol population. All subjects 
who meet the inclusion criteria, were seronegative at baseline, and do not 
have a major protocol deviation will be included in the per-protocol 
analysis. 
The All Subjects as Treated (ASaT) population will be used for the 
analysis of safety data in this study. The ASaT population consists of all 
randomized subjects who received at least one dose of study vaccination. 
Subjects will be included in the treatment group corresponding to the 
study treatment they actually received for the analysis of safety data using 
the ASaT population.  For most subjects this will be the treatment group 
to which they are randomized. Subjects who received incorrect study 
vaccine will be included in the treatment group corresponding to the study 
vaccine actually received.   
Statistical 
Methods 
for 
Immunogenicity Analyses 
Immunogenicity summaries will include: means and 95% CIs of the 
Geometric Mean Titers (GMT) and Geometric Mean Fold Increase from 
baseline (GMFI) of ZEBOV-specific antibody responses at baseline and 
Day 28, Day 84 (Cohort 5 only), Day 180, and Day 365.  
Immunogenicity summaries will include: counts, percentages, and 95% 
CIs of subjects who achieve seroconversion (e.g. 4-fold increase) for 

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ZEBOV-specific antibody responses at baseline and Day 28, Day 84 
(Cohort 5 only), Day 180, and Day 365. 
Immunogenicity summaries will include: counts, percentages, and 95% 
CIs of subjects who achieve seroprotection for ZEBOV-specific antibody 
responses at baseline and Day 28, Day 84 (Cohort 5 only), Day 180, and 
Day 365 based on correlate of protection thresholds, if found.  
Fisher’s exact (primary) or Chi-square test (secondary if sample size 
warrants) will be used to compare the frequency of ZEBOV-specific 
antibody responses and Student’s t (primary) or Wilcoxon rank-sum test 
(secondary if not normally distributed) will be used to compare ZEBOV-
specific GMT ZEBOV-specific antibody between treatment groups.  All 
hypotheses will be evaluated using two-sided tests at α = 0.05.  Superiority 
of immune response will be defined as a statistically significant difference.  
Statistical Methods for Safety 
Analyses 
Counts and percentages of solicited local and systemic reaction frequency 
and severity among study cohorts (various CD4 counts and ages) will be 
summarized.   
Fisher’s exact or Chi-square test will be used to compare the frequency of 
local and systemic reactions between treatment groups as specified in the 
SAP. 
Multiplicity 
Adjustment for multiplicity will not be performed.  
Sample Size and Power  
For immunogenicity assessment, there is 80% power to detect a Geometric 
Mean Ratio (GMR) of 1.6 (V920 GP-ELISA GMT of 58 EU/mL vs. 
Placebo GP-ELISA GMT of 36 EU/mL, the lower limit of quantification 
[LLOQ]) and 90% power to detect a GMR of 1.7 (V920 GP-ELISA GMT 
of 62 EU/mL) if comparing all five cohorts (N=200 V920 vs. N=50 
Placebo) combined.  This power analysis assumes a 10% dropout, a 
standard deviation of 1 on the log scale, and a 2-sided 5%. 
There is 80% power to detect a GMR of 2.9 (V920 GP-ELISA GMT of 
105 EU/mL) and 90% power to detect a GMR of 3.4 (V920 GP-ELISA 
GMT of 124 EU/mL) if comparing each cohort independently (N=40 
V920 vs. N=10 Placebo).  This power analysis assumes a 10% dropout, a 
standard deviation of 1 on the log scale, and a 2-sided 5%. 
For safety assessment, there is 80% power to detect a 12% difference in 
event rates that occur with a frequency of 1% in the control group if 
comparing all four cohorts (N=200 V920 vs. N=50 Placebo) combined 
and a 46% difference if comparing each cohort independently (N=40 
V920 vs. N=10 Placebo). 
Subgroup 
Analyses 
and 
Effect of Baseline Factors 
Safety, immunogenicity, seroprotection, and seroconversion will be 
summarized for these pre-specified subgroups: CD4 cell count (≥ 500 
cells/mm3, > 350 and < 500 cells/mm3, CD4 ≥ 200 and ≤ 350 cells/mm3), 
and age (adults, adolescents). 
Interim Analyses 
Four safety analyses will be conducted, one for each of the first four 
cohorts, when each cohort will have completed 42 days of follow-up post-
vaccination 
 

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8.2 
Statistical Analysis Plan Detailed Description 
8.2.1 Responsibility for Analyses/In-House Blinding 
The statistical analysis of the data obtained from this study will be the responsibility of the 
CIRN Biostatistics department.  
8.2.2 Objectives/Hypotheses 
(1) Objective:  Evaluate the safety and tolerability of V920 in HIV-infected adults and 
adolescents. 
 (2) Objective:  Evaluate the immunogenicity of V920 via ZEBOV-specific antibody 
responses induced by V920 at D28 in HIV-infected adults and adolescents. 
Primary Hypotheses:   
1) The geometric mean titer (GMT) of GP-ELISA in V920 vaccinated HIV-infected 
adults and adolescents will be superior to the GMT of the GP-ELISA in placebo 
vaccinated HIV-infected adults at Day 28 in Cohorts 1-5 combined.  
 
8.2.3 Analysis Endpoints 
8.2.3.1 Immunogenicity Endpoints 
The V920 vaccine candidate is a live recombinant vesicular stomatitis virus (VSV) expressing 
the glycoprotein (GP) of Zaire Ebola virus (ZEBOV). Two independent serological and 
molecular assays are currently being developed to clinically evaluate the immunogenicity of 
V920: 
▪ GP-ELISA measures the total IgG antibody response and can also be correlated to the 
plaque reduction neutralization assay (PRNT) titer result. 
▪ Plaque reduction neutralization assay (PRNT) is a functional assay for quantitating the 
neutralizing antibody response elicited by the vaccine.  
Participants who consent to bio-bank will undergo up to four blood draws in cohorts 1-4: at 
baseline on the day of vaccination before vaccine or placebo is administered; at D28 post-
vaccination; at D180 post-vaccination; and at D365 post-vaccination. 
 
8.2.4 Analysis Populations 
8.2.4.1 Immunogenicity Analysis Populations 
The Per-Protocol population (PP) will serve as the primary population for the analysis of 
immunogenicity data in this study. The Per-Protocol population excludes subjects due to 
important deviations from the protocol that may substantially affect the results of the primary 

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immunogenicity endpoint(s). For example, subjects who are seropositive at baseline will be 
excluded from the Per-Protocol population. All subjects who meet the inclusion criteria, were 
seronegative at baseline, and do not have a major protocol deviation will be included in the 
per-protocol analysis.  
The final determination of subjects with major protocol deviations, and thereby the 
composition of the Per- Protocol population, will be made prior to the unblinding of the 
database for the primary CSR (see Section 8.2.1) and will be documented in a separate memo. 
A supportive analysis using the Full Analysis Set (FAS) population may be performed. The 
FAS population consists of all randomized subjects with serology data. 
 
8.2.4.2 Safety Analysis Populations 
The All Subjects as Treated (ASaT) population will be used for the analysis of safety data in 
this study. The ASaT population consists of all randomized subjects who received at least one 
dose of study vaccination. Subjects will be included in the treatment group corresponding to 
the study treatment they actually received for the analysis of safety data using the ASaT 
population.  For most subjects this will be the treatment group to which they are randomized. 
Subjects who received incorrect study vaccine will be included in the treatment group 
corresponding to the study vaccine actually received.   
Details on the approach to handling missing data for safety analyses are provided in Section 
8.2.5 Statistical Methods. 
 
8.2.5 Statistical Methods 
8.2.5.1 Statistical Methods for Immunogenicity Analyses 
Immunogenicity summaries will include: means and 95% CIs of the Geometric Mean Titers 
(GMT) and Geometric Mean Fold Increase from baseline (GMFI) of ZEBOV-specific 
antibody responses at baseline and Day 28, Day 84 (Cohort 5 only), Day 180, and Day 365.  
Immunogenicity summaries will include: counts, percentages, and 95% CIs of subjects who 
achieve seroconversion (e.g. 4-fold increase) for ZEBOV-specific antibody responses at 
baseline and Day 28, Day 84 (Cohort 5 only), Day 180, and Day 365. 
Immunogenicity summaries will include: counts, percentages, and 95% CIs of subjects who 
achieve seroprotection for ZEBOV-specific antibody responses at baseline and Day 28, Day 
84 (Cohort 5 only), Day 180, and Day 365 based on correlate of protection thresholds, if found.  
Fisher’s exact (primary) or Chi-square test (secondary if proportion size warrants) will be used 
to compare the frequency of ZEBOV-specific antibody responses and Student’s t (primary) or 
Wilcoxon rank-sum test (secondary if not normally distributed) will be used to compare 
ZEBOV-specific GMT ZEBOV-specific antibody between treatment groups.  All hypotheses 
will be evaluated using two-sided tests at α = 0.05.  Superiority of immune response will be 
defined as a statistically significant difference. 

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8.2.5.2 Statistical Methods for Safety Analyses 
Safety parameters will be compared between V920 and placebo control.  Fisher’s exact or Chi-
square test will be used to compare the frequency of local and systemic reactions between 
treatment groups as specified in the SAP. 
 
Vaccine reactogenicity 
 
Counts and percentages of solicited local and systemic reaction frequency and severity among 
study cohorts (various CD4 counts and ages) will be summarized. 
 
Adverse events will be classified by Medical Dictionary for Regulatory Activities 
(MedDRA®) system organ class and preferred term, severity, seriousness, investigator 
causality assessment, and time since vaccination. 
 
Safety listings will display all safety events, including a separate display of solicited post-
treatment reactions, and all other AEs. 
 
Vital signs & clinical laboratory measures 
 
Mean values for each measure, including ± one standard deviation, will be summarized for 
each treatment group.  Shift tables may also be generated if a significant frequency of 
abnormalities is noted.  Extreme values will be discussed individually. 
 
8.2.5.3 Summaries of Baseline Characteristics, Demographics, and Other Analyses 
Continuous variables, such as age and weight, will be characterized by descriptive statistics.  
Categorical variables, such as ethnicity, will be displayed by percentage frequencies. 
8.2.6 Multiplicity 
Adjustment for multiplicity will not be performed.  
8.2.7 Sample Size and Power Calculations 
For immunogenicity assessment, there is 80% power to detect a Geometric Mean Ratio (GMR) 
of 1.6 (V920 GP-ELISA GMT of 58 EU/mL vs. Placebo GP-ELISA GMT of 36 EU/mL, the 
lower limit of quantification [LLOQ]) and 90% power to detect a GMR of 1.7 (V920 GP-
ELISA GMT of 62 EU/mL) if comparing all five cohorts (N=200 V920 vs. N=50 Placebo) 
combined.  This power analysis assumes a 10% dropout, a standard deviation of 1 on the log 
scale, and a 2-sided 5%. 
There is 80% power to detect a GMR of 2.9 (V920 GP-ELISA GMT of 105 EU/mL) and 90% 
power to detect a GMR of 3.4 (V920 GP-ELISA GMT of 124 EU/mL) if comparing each 
cohort independently (N=40 V920 vs. N=10 Placebo).  This power analysis assumes a 10% 
dropout, a standard deviation of 1 on the log scale, and a 2-sided 5%. 

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For safety assessment, there is 80% power to detect a 12% difference in event rates that occur 
with a frequency of 1% in the control group if comparing four cohorts (N=200 V920 vs. N=50 
Placebo) combined and a 46% difference if comparing each cohort independently (N=40 V920 
vs. N=10 Placebo). 
 
8.2.8 Subgroup Analyses and Effect of Baseline Factors 
Safety, immunogenicity, seroprotection, and seroconversion will be summarized for these pre-
specified subgroups: CD4 cell count (≥500 cells/mm3, >350 and <500 cells/mm3, CD4 ≥200 
and ≤350 cells/mm3), and age (adults, adolescents). 
8.2.9 Interim Analysis 
Four safety analyses will be conducted, one for each of the first four cohorts, when each cohort 
will have completed 42 days of follow-up post-vaccination. 
9.0 LABELING, PACKAGING, STORAGE AND RETURN OF CLINICAL 
SUPPLIES 
9.1 
Investigational Product  
The investigator shall take responsibility for and shall take all steps to maintain appropriate 
records and ensure appropriate supply, storage, handling, distribution and usage of 
investigational product in accordance with the protocol and any applicable laws and 
regulations. 
V920 vaccine supplies will be provided by the Manufacturer as summarized in Table 5 . 
Clinical supplies will be packaged to support enrollment as required.   
All subjects in Cohorts 1 to 4 will receive on D0 either the V920 (rVSVΔG-ZEBOV-GP) 
vaccine at a dose of ≥2x107 PFU in 1mL, or normal saline (0.9%) placebo control in 1mL. 
Subjects in Cohort 5 will also receive on D56 a matching dose of V920 at a dose of ≥2x107 
PFU in 1mL, or normal saline (0.9%) placebo control in 1mL. 
Placebo Control  
Normal saline (0.9%) has been chosen as an inert substance to serve as placebo control.  
Mode of Administration: 
The vaccine product is supplied as a single 1.0 mL dose in a sterile vial. Each vial contains 
vaccine virus frozen in a mixture of water for injection, 2.5 g/L recombinant human serum 
albumin, and 10 mM Tris.  After thawing, the content of the vial is a clear liquid. The V920 
vaccine candidate will be administered via intramuscular injection into the deltoid region 
of the upper extremity, using a 3-mL syringe with a 1-inch #23-gauge sterile needle 
(suggested). 
Treatment allocation 

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Participants will be randomized 4:1 (study vaccine: placebo control), with a total of 
approximately 200 study vaccine recipients and 50 placebo control recipients. 
 
Table 5: Product Descriptions 
 
Treatment 
Group 
 
Product Name 
and Dosage 
Form 
Dose/Potency 
Dose 
Frequency 
Total 
Dosage 
Forms 
Additional 
Information 
A 
V920 
≥2x107 PFU in 
1mL 
Once 
(Cohorts 1-
4) 
Twice 
(Cohort 5) 
IM 
Experimental 
B 
Normal 
saline 
(0.9%) 
1 mL 
Once 
(Cohorts 1-
4) 
Twice 
(Cohort 5) 
IM 
Placebo control 
V920 vaccine supplies will be provided by Manufacturer and shipped by Fisher Clinical 
Services. 
Any commercially available product not included in Table  will be provided by the trial site, 
subsidiary or designee. Every attempt should be made to source these supplies from a single 
lot/batch number. The trial site is responsible for recording the lot number, manufacturer, and 
expiry date for any locally purchased product as per local guidelines unless otherwise 
instructed by the Sponsor. 
9.2 
Packaging and Labeling Information 
Clinical supplies will be affixed with a clinical label in accordance with regulatory 
requirements. 
9.3 
Clinical Supplies Disclosure  
This trial is blinded but provided open label; therefore, an unblinded pharmacist or qualified 
trial site personnel will be used to prepare the vaccine. Both study vaccine and placebo are 
clear, and indistinguishable from one another once in the syringe.  Once the syringe is prepared, 
blinded personnel will administer the 1.0 ml study vaccine or placebo control to the subject.  
 
Vaccine identification information is to be unmasked ONLY if necessary for the welfare of the 
subject.  Every effort should be made not to unblind the subject unless necessary. 
In the event that unblinding has occurred, the circumstances around the unblinding (e.g., date 
and reason) must be documented promptly, and the Medical Monitor notified as soon as 
possible. Only the principal investigator or delegate and the respective subject’s code should 
be unblinded. Trial site personnel and Sponsor personnel directly associated with the conduct 
of the trial should not be unblinded. 

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9.4 
Storage and Handling Requirements 
Clinical supplies must be stored in a secure, limited-access location under the storage 
conditions specified on the label.   
Receipt and dispensing of trial medication must be recorded by an authorized person at the 
trial site.  
Clinical supplies may not be used for any purpose other than that stated in the protocol. 
9.5 
Discard/Destruction/Returns and Reconciliation 
The investigator is responsible for keeping accurate records of the clinical supplies received 
from the Sponsor or designee, the amount dispensed to and returned by the subjects and the 
amount remaining at the conclusion of the trial. For all trial sites, the local country Sponsor 
personnel or designee will provide appropriate documentation that must be completed for drug 
accountability and return, or local discard and destruction if appropriate.  Where local discard 
and destruction is appropriate, the investigator is responsible for ensuring that a local 
discard/destruction procedure is documented. 
9.6 
Standard Policies 
After unblinding, a letter is to be sent by the investigator to those subjects who received placebo 
control to provide the following:  
“You have participated in a trial of the Merck Ebola vaccine. This is to advise you that you 
were among those who received a placebo control.” 
A letter sent to subjects who received study vaccine should provide the following: 
“You have participated in a trial of the Merck Ebola vaccine. This is to advise you that you 
were among those who received the Ebola vaccine.” 
 
 
 

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10.0 LIST OF REFERENCES 
1. Intelligence CA. Ebola in West Africa:  The long term impact of the 2014 outbreak. 
Johannesburg: Consultancy Africa Intelligence; 2014. 
2. Team WHOER, Agua-Agum J, Ariyarajah A, et al. Ebola virus disease among children in 
West Africa. N Engl J Med 2015;372:1274-7. 
3. Mupapa K, Massamba M, Kibadi K, et al. Treatment of Ebola hemorrhagic fever with 
blood transfusions from convalescent patients. International Scientific and Technical 
Committee. J Infect Dis 1999;179 Suppl 1:S18-23. 
4. Jahrling PB, Geisbert TW, Geisbert JB, et al. Evaluation of immune globulin and 
recombinant interferon-alpha2b for treatment of experimental Ebola virus infections. J Infect 
Dis 1999;179 Suppl 1:S224-34. 
5. Jahrling PB, Geisbert J, Swearengen JR, et al. Passive immunization of Ebola virus-
infected cynomolgus monkeys with immunoglobulin from hyperimmune horses. Arch Virol 
Suppl 1996;11:135-40. 
6. Wilson JA, Hevey M, Bakken R, et al. Epitopes involved in antibody-mediated protection 
from Ebola virus. Science 2000;287:1664-6. 
7. Parren PW, Geisbert TW, Maruyama T, Jahrling PB, Burton DR. Pre- and postexposure 
prophylaxis of Ebola virus infection in an animal model by passive transfer of a neutralizing 
human antibody. J Virol 2002;76:6408-12. 
8. Oswald WB, Geisbert TW, Davis KJ, et al. Neutralizing antibody fails to impact the course 
of Ebola virus infection in monkeys. PLoS Pathog 2007;3:e9. 
9. Takada A, Ebihara H, Jones S, Feldmann H, Kawaoka Y. Protective efficacy of 
neutralizing antibodies against Ebola virus infection. Vaccine 2007;25:993-9. 
10. Qiu X, Wong G, Audet J, et al. Reversion of advanced Ebola virus disease in nonhuman 
primates with ZMapp. Nature 2014;514:47-53. 
11. Thi EP, Mire CE, Ursic-Bedoya R, et al. Marburg virus infection in nonhuman primates: 
Therapeutic treatment by lipid-encapsulated siRNA. Sci Transl Med 2014;6:250ra116. 
12. Quiroz E, Moreno N, Peralta PH, Tesh RB. A human case of encephalitis associated with 
vesicular stomatitis virus (Indiana serotype) infection. Am J Trop Med Hyg 1988;39:312-4. 
13. Cline BL. Ecological associations of vesicular stomatitis virus in rural Central America 
and Panama. Am J Trop Med Hyg 1976;25:875-83. 
14. Marzi A, Feldmann H, Geisbert TW, Falzarano D. Vesicular Stomatitis Virus-Based 
Vaccines for Prophylaxis and Treatment of Filovirus Infections. J Bioterror Biodef 2011;S1. 
15. Mire CE, Miller AD, Carville A, et al. Recombinant vesicular stomatitis virus vaccine 
vectors expressing filovirus glycoproteins lack neurovirulence in nonhuman primates. PLoS 
Negl Trop Dis 2012;6:e1567. 
16. Jones SM, Feldmann H, Stroher U, et al. Live attenuated recombinant vaccine protects 
nonhuman primates against Ebola and Marburg viruses. Nat Med 2005;11:786-90. 
17. Garbutt M, Liebscher R, Wahl-Jensen V, et al. Properties of replication-competent 
vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses. J 
Virol 2004;78:5458-65. 
18. TP M. Recombinant, chimeric, live, attenuated vaccines against flaviviruses and 
alphaviruses. In: Dormitzer PR MC, Rappuoli R, ed. Replicating Vaccines: Basel:  Springer 
Basel AG; 2011:349-438. 

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19. Jones SM, Stroher U, Fernando L, et al. Assessment of a vesicular stomatitis virus-based 
vaccine by use of the mouse model of Ebola virus hemorrhagic fever. J Infect Dis 2007;196 
Suppl 2:S404-12. 
20. Qiu X, Fernando L, Alimonti JB, et al. Mucosal immunization of cynomolgus macaques 
with the VSVDeltaG/ZEBOVGP vaccine stimulates strong ebola GP-specific immune 
responses. PLoS One 2009;4:e5547. 
21. Geisbert TW, Daddario-Dicaprio KM, Geisbert JB, et al. Vesicular stomatitis virus-based 
vaccines protect nonhuman primates against aerosol challenge with Ebola and Marburg 
viruses. Vaccine 2008;26:6894-900. 
22. Marzi A, Robertson SJ, Haddock E, et al. EBOLA VACCINE. VSV-EBOV rapidly 
protects macaques against infection with the 2014/15 Ebola virus outbreak strain. Science 
2015;349:739-42. 
23. Feldmann H, Jones SM, Daddario-DiCaprio KM, et al. Effective post-exposure treatment 
of Ebola infection. PLoS Pathog 2007;3:e2. 
24. Geisbert TW, Daddario-Dicaprio KM, Lewis MG, et al. Vesicular stomatitis virus-based 
ebola vaccine is well-tolerated and protects immunocompromised nonhuman primates. PLoS 
Pathog 2008;4:e1000225. 
25. Kennedy SB, Neaton JD, Lane HC, et al. Implementation of an Ebola virus disease vaccine 
clinical trial during the Ebola epidemic in Liberia: Design, procedures, and challenges. Clin 
Trials 2016. 
26. Henao-Restrepo AM, Longini IM, Egger M, et al. Efficacy and effectiveness of an rVSV-
vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring 
vaccination cluster-randomised trial. Lancet 2015;386:857-66. 
27. Gunther S, Feldmann H, Geisbert TW, et al. Management of accidental exposure to Ebola 
virus in the biosafety level 4 laboratory, Hamburg, Germany. J Infect Dis 2011;204 Suppl 
3:S785-90. 
28. Lai L, Davey R, Beck A, et al. Emergency postexposure vaccination with vesicular 
stomatitis virus-vectored Ebola vaccine after needlestick. JAMA 2015;313:1249-55. 
29. Cnops L, Gerard M, Vandenberg O, et al. Risk of Misinterpretation of Ebola Virus PCR 
Results After rVSV ZEBOV-GP Vaccination. Clin Infect Dis 2015;60:1725-6. 
30. Agnandji ST, Huttner A, Zinser ME, et al. Phase 1 Trials of rVSV Ebola Vaccine in Africa 
and Europe - Preliminary Report. N Engl J Med 2015. 
 
 

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11.0  APPENDIX 1: LIST OF ABBREVIATIONS: 
Abbreviation/Acrony
m 
Definition 
AE 
Adverse Event 
AR 
Adverse Reactions 
CD 
Cluster Designation 
CDC 
Centers for Disease Control and Prevention 
CIRN 
Canadian Immunization Research Network 
cDNA 
Complementary Deoxyribonucleic Acid 
cGLP 
Current Good Laboratory Practices 
D 
Day 
CMH 
Cochran-Mantel-Haenszel 
CVA 
Cerebrovascular Accident 
DHHS 
Department of Health and Human Services 
DNA 
Deoxyribonucleic Acid 
DSMB 
Data and Safety Monitoring Board 
EBOV 
Ebola virus 
ELISA 
Enzyme-Linked Immunosorbent Assay 
EU 
European Union 
EVD 
Ebola Virus Disease 
FLW 
Front Line Workers 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMO 
Genetically Modified Organism 
GMR 
Geometric Mean Ratio 
GMT 
Geometric Mean Titer 
GP 
Glycoprotein 
HIV 
Human Immunodeficiency Virus 
HSA 
Human Serum Albumin 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation 
IEC 
Institutional Ethics Committee 
IRB 
Institutional Review Board 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
IM 
Intramuscular 
LLOQ 
Lower Limit of Quantification 
MARV 
Marburg Virus 
MedDRA 
Medical Dictionary for Regulatory Activities 
mL 
Milliliter(s) 
MRI 
Magnetic Resonance Imaging 
MSF 
Médecins Sans Frontières 
NIH 
National Institutes of Health 

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Abbreviation/Acrony
m 
Definition 
NHP 
Non-Human Primates 
NSAID 
Non-Steroidal Anti-Inflammatory Drugs 
OD 
Optical Density 
PCR 
Polymerase Chain Reaction 
PFU 
Plaque Forming Units 
PHAC 
Public Health Agency of Canada 
PRNT 
Plaque Reduction Neutralization Assay 
PsVNA 
Pseudovirion Neutralizing Assay 
qRT-PCR 
Quantitative Reverse-Transcriptase Polymerase Chain 
Reaction 
RNA 
Ribonucleic Acid 
RT-PCR 
Reverse-Transcriptase Polymerase Chain Reaction 
rVSVΔG-ZEBOV-GP 
Recombinant Vesicular Stomatitis Virus with Envelope 
Glycoprotein replaced by Zaire ebolavirus (Kikwit Strain) 
Glycoprotein (V920) 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
sSAP 
Supplemental Statistical Analysis Plan 
SEBOV 
Sudan ebolavirus 
SHIV 
Simian Immunodeficiency Virus 
siRNA 
Small Interfering Ribonucleic Acid 
SMC 
Safety Monitoring Committee 
TCID 
Tissue Culture Infective Dose 
TILDA 
Tat/rev Induced Limiting Dilution Assay 
TSC 
Trial Steering Committee 
USAMRIID 
United States Army Medical Research Institute for 
Infectious Diseases 
USP 
United States Pharmacopeia 
VSV 
Vesicular Stomatitis Virus 
WBC 
White Blood Cell 
WHO 
World Health Organization 
WRAIR 
Walter Reed Army Institute of Research 
V920 
rVSVΔG-ZEBOV-GP  
ZEBOV 
Zaire ebolavirus 
 
 
 

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12.0 APPENDIX 2: LABORATORY ABNORMALITIES* 
Grade 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4)** 
Serum * 
Sodium – Hyponatremia mEq/L 
132 – 134 
130 – 131 
125 – 129 
< 125 
Sodium – Hypernatremia mEq/L 
144 – 145 
146 – 147 
148 – 150 
> 150 
Potassium – Hyperkalemia mEq/L 
5.1 – 5.2 
5.3 – 5.4 
5.5 – 5.6 
> 5.6 
Potassium – Hypokalemia mEq/L 
3.5 – 3.6 
3.3 – 3.4 
3.1 – 3.2 
< 3.1 
Glucose – Hypoglycemia mg/dL 
65 – 69 
55 – 64 
45 – 54 
< 45 
Glucose – Hyperglycemia 
Fasting – mg/dL 
Random – mg/dL 
  
100 – 110 
110 – 125 
  
111 – 125 
126 – 200 
  
>125 
>200 
Insulin requirements 
or hyperosmolar 
coma 
Blood Urea Nitrogen 
BUN mg/dL 
23-26 
27 – 31 
> 31 
Requires dialysis 
Creatinine – mg/dL 
1.5 – 1.7 
1.8 – 2.0 
2.1 – 2.5 
> 2.5 or requires 
dialysis 
Calcium – hypocalcemia mg/dL 
8.0 – 8.4 
7.5 – 7.9 
7.0 – 7.4 
< 7.0 
Calcium – hypercalcemia mg/dL 
10.5 – 11.0 
11.1 – 11.5 
11.6 – 12.0 
> 12.0 
Magnesium – hypomagnesemia 
mg/dL 
1.3 – 1.5 
1.1 – 1.2 
0.9 – 1.0 
< 0.9 
Phosphorous – hypophosphatemia 
mg/dL 
2.3 – 2.5 
2.0 – 2.2 
1.6 – 1.9 
< 1.6 
CPK – mg/dL 
1.25 – 1.5 x 
ULN*** 
1.6 – 3.0 x 
ULN 
3.1 –10 x ULN > 10 x ULN 
Albumin – Hypoalbuminemia g/dL 
2.8 – 3.1 
2.5 – 2.7 
< 2.5 
-- 
Total Protein – Hypoproteinemia 
g/dL 
5.5 – 6.0 
5.0 – 5.4 
< 5.0 
-- 
Alkaline phosphate – increase by 
factor 
1.1 – 2.0 x 
ULN 
2.1 – 3.0 x 
ULN 
3.1 – 10 x 
ULN 
> 10 x ULN 
Liver Function Tests –ALT, AST 
increase by factor 
1.1 – 2.5 x 
ULN 
2.6 – 5.0 x 
ULN 
5.1 – 10 x 
ULN 
> 10 x ULN 
Bilirubin – when accompanied by 
any increase in Liver Function Test 
increase by factor 
1.1 – 1.25 x 
ULN 
1.26 – 1.5 x 
ULN 
1.51 – 1.75 x 
ULN 
> 1.75 x ULN 

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Bilirubin – when Liver Function Test 
is normal; increase by factor 
1.1 – 1.5 x 
ULN 
1.6 – 2.0 x 
ULN 
2.0 – 3.0 x 
ULN 
> 3.0 x ULN 
Cholesterol 
201 – 210 
211 – 225 
> 226 
--- 
Pancreatic enzymes – amylase, lipase 1.1 – 1.5 x 
ULN 
1.6 – 2.0 x 
ULN 
2.1 – 5.0 x 
ULN 
> 5.0 x ULN 
Hematology * 
Hemoglobin (Female) - gm/dL 
11.0 – 12.0 
9.5 – 10.9 
8.0 – 9.4 
< 8.0 
Hemoglobin (Female) change from 
baseline value - gm/dL 
Any decrease – 
1.5 
1.6 – 2.0 
2.1 – 5.0 
> 5.0 
Hemoglobin (Male) - gm/dL 
12.5 – 13.5 
10.5 – 12.4 
8.5 – 10.4 
< 8.5 
Hemoglobin (Male) change from 
baseline value – gm/dL 
Any decrease – 
1.5 
1.6 – 2.0 
2.1 – 5.0 
> 5.0 
WBC Increase - cell/mm3 
10,800 – 
15,000 
15,001 – 
20,000 
20,001 – 25, 
000 
> 25,000 
WBC Decrease - cell/mm3 
2,500 – 3,500 
1,500 – 2,499 
1,000 – 1,499 
< 1,000 
Lymphocytes Decrease - cell/mm3 
750 – 1,000 
500 – 749 
250 – 499 
< 250 
Neutrophils Decrease - cell/mm3 
1,500 – 2,000 
1,000 – 1,499 
500 – 999 
< 500 
Eosinophils - cell/mm3 
650 – 1500 
1501 - 5000 
> 5000 
Hypereosinophilic 
Platelets Decreased - cell/mm3 
125,000 – 
140,000 
100,000 – 
124,000 
25,000 – 
99,000 
< 25,000 
PT – increase by factor (prothrombin 
time) 
1.0 – 1.10 x 
ULN** 
ï€ 1.11 – 1.20 
x ULN 
1.21 – 1.25 x 
ULN 
> 1.25 ULN 
PTT – increase by factor (partial 
thromboplastin time) 
1.0 – 1.2 x 
ULN 
1.21 – 1.4 x 
ULN 
1.41 – 1.5 x 
ULN 
> 1.5 x ULN 
Fibrinogen increase - mg/dL 
400 – 500 
501 – 600 
> 600 
-- 
Fibrinogen decrease - mg/dL 
150 – 200 
125 – 149 
100 – 124 
< 100 or associated 
with gross bleeding 
or disseminated 
intravascular 
coagulation (DIC) 
Urine * 
Protein 
Trace 
1+ 
2+ 
Hospitalization or 
dialysis 
Glucose 
Trace 
1+ 
2+ 
Hospitalization 
forhyperglycemia 

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Blood (microscopic) - red blood cells 
per high power field (rbc/hpf) 
1 - 10 
11 - 50 
> 50 and/or 
gross blood 
Hospitalization or 
packed red blood 
cells (PRBC) 
transfusion 
 
* The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal 
parameters. Institutional normal reference ranges should be provided to demonstrate that they are appropriate. 
** The clinical signs or symptoms associated with laboratory abnormalities might result in characterization of 
the laboratory abnormalities as Potentially Life Threatening (Grade 4). For example. a low sodium value that 
falls within a grade 3 parameter (125-129 mE/L) should be recorded as a grade 4 hyponatremia event if the 
subject had a new seizure associated with the low sodium value. 
***ULN" is the upper limit of the normal range. 
 

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13.0 APPENDIX 3: STOPPING RULES 
The DSMB will be provided with the following stopping rules as guidance for temporarily 
halting or terminating the study: 
If any of the following events occurs, administration of study vaccine will be temporarily 
on hold until a thorough review of accumulated safety data is undertaken by the DSMB, 
the investigator, and /or the SPONSOR’s representative. 
• Death in any subject if considered related to administration of the test vaccine; 
• Unexpected life-threatening event in any subject if considered related to administration 
of the test vaccine, unless already reported for V920; 
• Serious adverse event in any subject if considered related to administration of the test 
vaccine, unless already reported for V920; 
• Event which in the opinion of the investigator and/or safety monitoring committee 
contraindicates further dosing of additional subjects.