A Phase I Open-Label, Dose-Escalation Clinical Trial to Evaluate the Safety, Tolerability and Immunogenicity of Two Doses of an Ebola Sudan Chimpanzee Adenovirus Vector Vaccine, VRC-EBOADC086-00-VP (cAd3-EBO S), in Healthy Adults
Phase: PHASE1
Conditions: Ebola Virus
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

OfficialTitle:APhaseIOpen-Label,Dose-EscalationClinicalTrialtoEvaluatetheSafety,Tolerability
andImmunogenicityofTwoDosesofanEbolaSudanChimpanzeeAdenovirusVectorVaccine,
VRC-EBOADC086-00-VP(cAd3-EBOS),inHealthyAdults
ClinicalTrials.govIdentifier:NCT04041570

DocumentType:
·
RedactedFinalVersionoftheStudyProtocol(StatisticalAnalysisConsiderationslocatedin
Section8oftheProtocol)
·
RedactedFinalVersionsofIRB-approvedInformedConsents

Document/Date:
·
ProtocolVersion1.5:March3,2020
·
FinalIRB-approvedInformedConsents:March3,2020
o Version1.5MainStudy
o Version1.5FutureUseofStoredSpecimens
o Version1.5GeneticTesting
o Version1.5WithdrawSample

RV508/WRAIR#2439
Version1.5
03March2020
ProtocolRV508

APhaseIOpen-Label,Dose-EscalationClinicalTrialtoEvaluatetheSafety,
TolerabilityandImmunogenicityofTwoDosesofanEbolaSudan
ChimpanzeeAdenovirusVectorVaccine,VRC-EBOADC086-00-VP(cAd3-
EBOS),inHealthyAdults


StudyProductProvidedBy
NationalInstitutesofHealth(NIH)
NationalInstituteofAllergyandInfectiousDiseases(NIAID)
VaccineResearchCenter(VRC)
Bethesda,Maryland


StudyConductedBy
MakerereUniversity-WalterReedProject,MakerereUniversity,Kampala,Uganda


InConsultationWith
U.S.MilitaryHIVResearchProgram(MHRP)SilverSpring,MD
VRC,NIAID,NIH


StudySponsoredby
NationalInstitutesofHealth(NIH)
NationalInstituteofAllergyandInfectiousDiseases(NIAID)
VaccineResearchCenter(VRC)
Bethesda,Maryland


StudyFundedBy
NationalInstitutesofHealth(NIH)
and
U.S.MilitaryHIVResearchProgram
throughthe
CooperativeAgreement


IND#16111–heldbyVRC,NIAID,NIH



PrincipalInvestigator:
BettyMwesigwa,MBChB,MScClinicalTrials
INDMedicalOfficer:
LCDRMartinGaudinski,M.D.
DoDResearchMonitor:
MosesKamya,MBChB,MMED,MPH,PhD

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TABLEOFCONTENTS
SCHEMA.......................................................................................................................................6 
LISTOFABBREVIATIONS......................................................................................................9 
1.0 
INTRODUCTION.............................................................................................................11 
1.1 
Background:EbolaInfection.........................................................................................11 
1.2 
RationalefortheEbolaSudanChimpanzeeAdenovirusVectorVaccine,VRC-
EBOADC086-00-VP(cAd3-EBOS)andRV508StudyDesign..............................12 
1.2.1 PreviousHumanExperiencewithVRCFilovirusVaccines................................12 
1.2.2 PreviousHumanExperiencewithChimpanzeeAdenovirusVectorSerotype3
(cAd3)..............................................................................................................16 
1.3 
PreclinicalStudiesSupportingtheSafetyofVRC-EBOADC086-00-VP(cAd3-EBO
S).................................................................................................................................17 
1.4 
NonclinicalImmunogenicityandProtectionStudiesofcAd3Constructs....................18 
1.5 
DoseJustificationforcAd3-EBOS...............................................................................19 
2.0 
STUDYOBJECTIVES.....................................................................................................20 
2.1 
PrimaryObjectives........................................................................................................20 
2.2 
SecondaryObjectives....................................................................................................20 
2.3 
ExploratoryObjectives..................................................................................................20 
3.0 
ENDPOINTS......................................................................................................................21 
3.1 
PrimaryEndpoints:Safety.............................................................................................21 
3.2 
SecondaryEndpoints:Immunogenicity.........................................................................21 
3.3 
ExploratoryEndpoints...................................................................................................21 
4.0 
STUDYDESIGNANDPOPULATION..........................................................................22 
4.1 
Eligibility.......................................................................................................................22 
4.1.1 InclusionCriteria..................................................................................................22 
4.1.2 ExclusionCriteria.................................................................................................23 
5.0 
STUDYPROCEDURES...................................................................................................26 
5.1 
ScheduleofEvaluations.................................................................................................26 
5.2 
Recruitment,Consent,ScreeningandEnrollment.........................................................26 
5.2.1 ConsentProceduresandScreening.......................................................................26 
5.2.2 Day0ThroughWeek48.......................................................................................27 
5.3 
AdministrationoftheStudyInjectionandOn-StudyAssessments...............................28 
5.3.1 7-DaySolicitedReactogenicity............................................................................28 
5.3.2 ManagementofReactogenicityAdverseEventsFollowingStudyVaccinations 29 
5.3.3 ManagementofLaboratoryAbnormalitiesAfterVaccination.............................29 
5.4 
ConcomitantMedications..............................................................................................29 
5.5 
StudyDiscontinuation....................................................................................................30 
5.5.1 EarlyDiscontinuationorWithdrawalofStudyParticipants.................................30 
5.6 
ManagementofParticipantsWhoBecomePregnant....................................................30 
5.7 
ManagementofParticipantsWhoBecomeIncarcerated...............................................31 
5.8 
ManagementandCounselingofParticipantswithPositiveHIVorSyphilisTest........31 
6.0 
PHARMACYANDVACCINEADMINISTRATIONPROCEDURES......................32 
6.1 
Regimens.......................................................................................................................32 
6.2 
StudyProductFormulation,Preparation,andStorage..................................................32 

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6.2.1 Formulation...........................................................................................................32 
6.2.2 StudyProductLabels............................................................................................32 
6.2.3 StudyProductStorage...........................................................................................33 
6.2.4 PreparationofStudyProductforInjection...........................................................33 
6.3 
Pharmacy:ProductSupply,Distribution,andAccountability.......................................33 
6.3.1 StudyProductAcquisition/Distribution................................................................33 
6.3.2 StudyProductAccountability...............................................................................34 
6.3.3 DisposalofClinicalSupplies................................................................................34 
7.0 
PHARMACOVIGILENCE,SAFETY,ANDADVERSEEVENTREPORTING......35 
7.1 
Definitions.....................................................................................................................35 
7.2 
AdverseEventGradingandRecording.........................................................................35 
7.2.1 GradingandRecordingTachypnea......................................................................36 
7.3 
ProtocolSafetyReviewTeam.......................................................................................36 
7.4 
SafetyMonitoringCommittee(SMC)Reviews............................................................37 
7.5 
CriteriaforStudyPauseorTermination........................................................................37 
7.6 
ReportingSeriousandUnexpectedAdverseEvents.....................................................38 
7.6.1 StudyReportingPeriodforSAEs.........................................................................38 
7.6.2 AdverseEventReportingtotheINDSponsor......................................................38 
7.6.3 INDSponsorReportingtotheFDA.....................................................................39 
7.6.4 ReportingSeriousandUnexpectedAdverseEventstotheLocalRegulatory
Bodies&InstitutionalReviewBoards.............................................................39 
7.6.5 ReportingSeriousandUnexpectedAdverseEventstoWRAIRandHRPO........40 
7.7 
UnanticipatedProblemsReporting................................................................................40 
8.0 
STATISTICALCONSIDERATIONS.............................................................................41 
8.1 
Overview........................................................................................................................41 
8.2 
SampleSizeandAccrual...............................................................................................41 
8.2.1 PowerandSampleSizeCalculationsforSafety...................................................41 
8.2.2 PowerandSampleSizeCalculationsforImmunogenicity...................................42 
8.3 
StatisticalAnalysis.........................................................................................................42 
8.3.1 BaselineDemographics........................................................................................42 
8.3.2 SafetyAnalysis.....................................................................................................42 
8.3.3 ImmunogenicityAnalysis.....................................................................................43 
8.3.4 InterimAnalyses...................................................................................................43 
9.0 
SAMPLEANDDATAMANAGEMENT.......................................................................44 
9.1 
PlanforUseandStorageofBiologicalSamples...........................................................44 
9.1.1 UseofSamples,SpecimensandData...................................................................44 
9.1.2 StorageandTrackingofBloodSamplesandOtherSpecimens...........................44 
9.1.3 DispositionofSamples,SpecimensandDataatCompletionoftheProtocol......45 
9.1.4 LossorDestructionofSamples,SpecimensorData............................................45 
9.2 
StudyDocumentationandStorage................................................................................45 
9.3 
DataCollection..............................................................................................................46 
10.0 ETHICALCONSIDERATIONS......................................................................................47 
10.1 Risks...............................................................................................................................47 
10.1.1 RisksofthecAd3EbolaVaccinesandDiluent....................................................47 
10.1.2 OtherRisks............................................................................................................47 
10.2 Benefits..........................................................................................................................48 

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10.3 InformedConsent..........................................................................................................48 
10.4 Language........................................................................................................................49 
10.5 Compensation................................................................................................................49 
10.6 PolicyRegardingResearch-RelatedInjuries.................................................................49 
10.7 ParticipantConfidentiality.............................................................................................49 
10.8 FutureUseandStorageofBloodSamples....................................................................50 
11.0 REGULATORYREPORTINGREQUIREMENTS......................................................51 
11.1 ProtocolDeviationReporting........................................................................................51 
11.2 SafetyReports................................................................................................................51 
11.3 Pregnancies....................................................................................................................51 
11.4 StudyHolds....................................................................................................................51 
11.5 ProtocolModifications..................................................................................................52 
11.6 ContinuingReviews/CloseoutReport...........................................................................52 
11.7 ReportingRequirementstotheMRDCORPHRPO.....................................................53 
11.8 UseofInformationandPublication...............................................................................54 
12.0 CONDUCTOFTHERESEARCHSTUDY...................................................................55 
12.1 RegulatoryAudits..........................................................................................................55 
12.2 ProtocolMonitoringPlan...............................................................................................55 
13.0 PRINCIPALINVESTIGATORAGREEMENT............................................................56 
14.0 REFERENCES...................................................................................................................57 
APPENDIX1:SCHEDULEOFEVALUATIONS..................................................................59 
APPENDIX2:INFORMEDCONSENTFORMS...................................................................61 
APPENDIX2A:MAININFORMEDCONSENTFORM......................................................62 
APPENDIX2B:FUTUREUSEINFORMEDCONSENTFORM........................................75 
APPENDIX2C:INFORMEDCONSENTFORGENETICTESTING...............................79 
APPENDIX2D:WITHDRAWALOFCONSENTFORSAMPLESTORAGE.................83 
APPENDIX3:VOLUNTEEREVENTSCHEDULE.............................................................85 
APPENDIX4:ASSESSMENTOFUNDERSTANDING.......................................................88 
APPENDIX5:BRIEFINGSLIDES.........................................................................................91 
APPENDIX6:GRADINGSEVERITYOFADVERSEEVENTS......................................109 
APPENDIX7:DAIDSTABLEFORGRADINGSEVERITYOFARTHRALGIA
ADVERSEEVENTS....................................................................................................115 
APPENDIX8:STUDYTEAMROSTER...............................................................................116 
APPENDIX9:ROLESANDRESPONSIBILITIES.............................................................121 
APPENDIX10:DIARYCARD...............................................................................................124 
APPENDIX11:RECRUITMENTMATERIALS.................................................................136 
APPENDIX12:APPOINTMENT/EMERGENCYCONTACTCARD.............................142 
APPENDIX13:LISTOFEXTERNALCOLLABORATORS............................................144 

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LISTOFTABLES
Table1: 
RV508StudyDesign...................................................................................................6 
Table2: 
SummaryoftheStudiesforEvaluationofVRCEbolaandMarburg
Vaccines......................................................................................................................13 
Table3. 
PreclinicalProof-of-ConceptStudiesinCynomolgusMacaques..............................18 
Table4. 
Exact95%ConfidenceIntervalsfortheProportionofParticipants
ExperiencingaSafetyEvent.......................................................................................41 
Table5 
MinimumDetectableDifferences,inStandardDeviations,forChangeFrom
BaselinetoaSingleTime(2-sidedα=0.05)...............................................................42 


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SCHEMA
Title
APhaseIOpen-Label,Dose-EscalationClinicalTrialtoEvaluatetheSafety,Tolerabilityand
Immunogenicity of Two Doses of an Ebola Sudan Chimpanzee Adenovirus Vector Vaccine,
VRC-EBOADC086-00-VP(cAd3-EBOS),inHealthyAdults
StudyDesign
This is a Phase I, open-label study to examine safety, tolerability and immunogenicity of an
investigationalEbolavaccinegivenbyintramuscular(IM)injectiontohealthyadults.Thestudy
isadoseescalationofVRC-EBOADC086-00-VP,achimpanzeeadenovirusserotype3vector
vaccine,whichencodeswildtype(WT)glycoprotein(GP)fromtheSudanstrainofEbolavirus.
Table1:
RV508StudyDesign
Group
Participants
Day0*
1
20
cAd3-EBOSat1x1010PU/mL
2
20
cAd3-EBOSat1x1011PU/mL
*Allinjections:administeredin1mLvolume.
It is anticipated that about 100 volunteers will be screened in order to enroll a total of 40
participants.The40participantswillbeevenlysplit,with20ineachofthetwodosagegroups
forcAd3-EBOS.Thedoseescalationplanincludesdailyreviewofanynewsafetydatabya
studyclinician,regularreviewofsafetydatabytheprotocolteamandastagedenrollmentplan
withrequiredinterimsafetyreviews.Thestudywillbeginwithenrollmentof3participantsinto
Group 1 at a rate of 1 participant per day. After at least 7 days of follow-up for the first 3
vaccinated participants, an interim safety review will occur before enrollment of additional
participantsintothegroup.Ifnosafetyissuesareidentified,anadditional17participantswillbe
enrolledtocompleteGroup1.Whenthereisaminimumofsevendaysoffollow-upsafetydata
fromthelastenrolledparticipantinGroup1,aninterimsafetyreviewwilloccur.Oncenosafety
issuesareidentified,enrollmentofparticipantsintothenextdoselevel(Group2)willbeginwith
theenrollmentof3participantsatarateof1participantperday.Afteratleast7daysoffollow-
upforthefirst3vaccinatedparticipantsinGroup2,aninterimsafetyreviewwilloccurbefore
the enrollment of additional participants into Group 2. If no safety issues are identified, an
additional17participantswillbeenrolledtocompleteGroup2.
ProductDescription
VRC-EBOADC086-00-VP(cAd3-EBOS)iscomposedofacAd3vectorthatexpressesEbola
SudanWTGP.Itisformulatedat1x1011PU/mL.
VRC-DILADC065-00-VP(diluent) isthe formulation buffer usedfor vaccine production and
willbeusedwhenneededtopreparethe1x1010PU/mLdoseofcAd3-EBOS.
Participants
HealthyadultsintheKampalaareaaged18-50yearswillbeenrolled.

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StudyDuration
Participantswillbeevaluatedat9clinicvisitsover48weeks.
StudyObjectives
PrimaryObjectives
· ToevaluatethesafetyandtolerabilityofVRC-EBOADC086-00-VPwhenadministered
IMatadoseof1x1010particleunits(PU)tohealthyadults;
· ToevaluatethesafetyandtolerabilityofVRC-EBOADC086-00-VPwhenadministered
IMatadoseof1x1011PUtohealthyadults.
SecondaryObjectives
· ToevaluatetheantibodyresponsetotheGPinsertandcAd3vectorinVRC-
EBOADC086-00-VPat4weeksaftervaccinationasassessedbyGPELISAandvector-
specificneutralizationassays,respectively.
· ToevaluatetheEbolaSudanGP-specificTcellresponsesinVRC-EBOADC086-00-VP
at4weeksaftervaccinationasassessedbyIntracellularcytokinestaining(ICS).
ExploratoryObjectives
· ToevaluatetheimmunogenicityofVRC-EBOADC086-00-VPbyvariousassaymethods
atsomeoralloftheresearchsamplecollectiontimepointsindicatedintheScheduleof
Evaluations(SOE);geneticfactorsassociatedwithimmuneresponsemayalsobe
evaluated.
· Toevaluatevaccine-inducedmRNAexpressionprofilesthroughStudyWeek1.
· ToevaluatethetimecourseanddurabilityofcAd3neutralizingantibodytiters,mediators
ofinflammationfollowingvaccinationandtimecourseanddurabilityofimmune
responsebyavarietyofexploratoryassaysusingsamplescollectedthroughoutthestudy.
· ToisolateMonoclonalAntibodies(MAbs)todetermineepitopespecificityandtheir
functionalcapacity.
StudyClinicalSite
MakerereUniversity-WalterReedProject
Kampala,Uganda
StudyLaboratory
MakerereUniversity–WalterReedProjectLaboratory
Kampala,Uganda

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NIAIDVaccineImmunologyProgram(VIP)
NIAIDVRCImmunologyLaboratory
StudyDataManagementCenter
EMMESCorporation
ReviewingIRBs
MakerereUniversitySchoolofPublicHealth(MUSPH)IRB
HigherDegrees,ResearchandEthicsCommittee
(FWA00011353,IRB00005876)
Kampala,Uganda
LocalRegulatoryAuthorities
UgandaNationalCouncilofScienceandTechnology
(FWA00001293,IORG0001117)
,
Kampala,Uganda
NationalDrugAuthority(NDA)
Kampala,Uganda

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LISTOFABBREVIATIONS
Abbreviation
Term
Ad5
Humanadenovirusserotype5
ADL
Activitiesofdailyliving
AE
Adverseevent
ALT
Alanineaminotransferase
AoU
Assessmentofunderstanding
APA
Anti-phospholipidantibody
BDBV
SpeciesBundibugyoebolavirus
BMI
Bodymassindex
cAd
Recombinantchimpanzeeadenovirus
cAd3
Recombinantchimpanzeeadenovirusserotype3
cAd3-EBO
Recombinant chimpanzeeadenovirustype3-vectoredEbolavirus
vaccine
cAd63
Recombinantchimpanzeeadenovirusserotype63
CBC
Completebloodcount
cGMP
CurrentGoodManufacturingPractices
DNA
Deoxyribonucleicacid
EBOV
SpeciesZaireebolavirus
EHF
Ebolahemorrhagicfever
ELISA
Enzyme-linkedimmunosorbentassay
ELISPOT
Enzyme-linkedimmunospot
EVD
Ebolavirusdisease
FDA
FoodandDrugAdministration
GCP
GoodClinicalPractices
GLP
GoodLaboratoryPractices
GP
Glycoprotein
GP(S)
GlycoproteinfromSudanebolavirus
GP(Z)
GlycoproteinfromZaireebolavirus
HA
Influenzahemagglutininprotein
HAE
Hereditaryangioedema
HCV
HepatitisCvaccine
HIV
Humanimmunodeficiencyvirus
HLA
Humanleukocyteantigen
IB
Investigator’sBrochure
ICS
Intracellularcytokinestaining
ICTV
InternationalCommitteeontheTaxonomyofViruses
IgG
ImmunoglobulinG
IgM
ImmunoglobulinM
IM
Intramuscular
IND
Investigationalnewdrug
IP
Investigationalproduct
IRB
InstitutionalReviewBoard
LIMS
LaboratoryInformationManagementSystem
MAbs
MonoclonalAntibodies

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MHRP
U.S.MilitaryHIVResearchProgram
NHP
Non-humanprimate
NIAID
NationalInstituteofAllergyandInfectiousDiseases
NIH
NationalInstitutesofHealth
NP
Nucleoprotein
NSAID
Nonsteroidalanti-inflammatorydrug
PBMC
Peripheralbloodmononuclearcells
PFU
Particleformingunits
PSRT
ProtocolSafetyReviewTeam
PT
Prothrombintime
PTT
Partialthromboplastintime
PU
Particleunits
rAd
Recombinanthumanadenovirus
rAd5
Recombinanthumanadenovirusserotype5
RESTV
SpeciesRestonebolavirus
RNA
Ribonucleicacid
RPR
Rapidplasmareagin
SAE
Seriousadverseevent
SAS
StatisticalAnalysisSystem
SUDV
SpeciesSudanebolavirus
SUSAR
Suspected,unexpectedandseriousadversereaction
TAFV
SpeciesTaïForestebolavirus
ULN
Upperlimitofnormal
VCMP
VaccineClinicalMaterialsProgram
VIP
NIAIDVaccineImmunology Program
VP
Virusparticle
VPP
VRCPilotPlant
VRC
VaccineResearchCenter
WBC
Whitebloodcell
WHO
WorldHealthOrganization
WRAIR
WalterReedArmyInstituteofResearch
WT
Wildtype


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1.0
INTRODUCTION
1.1
Background:EbolaInfection
In 2013,the InternationalCommitteeon the Taxonomy of Viruses (ICTV) Filoviridae Study
Groupandotherexpertspublishedanupdatedtaxonomyforfiloviruses.ThegenusEbolavirusis
oneofthreegenerainthefamilyFiloviridae,whichalongwiththegenera,Marburgvirusand
Cuevavirus,areknowntoinduceviralhemorrhagicfever.Fivedistinctspeciesincludedinthe
genus Ebolavirus are Bundibugyo (BDBV), Reston (RESTV), Sudan (SUDV), Taï Forest
(TAFV),andZaire(EBOV)[1].
Ebolavirusisalarge,negative-strandRNAviruscomposedof7genesencodingviralproteins,
including a single glycoprotein (GP) [2-5]. The virus is responsible for causing Ebola virus
disease (EVD), formerly known asEbolahemorrhagicfever (EHF), inhumans. Inparticular,
BDBV, EBOV, and SUDV havebeenassociated withlargeoutbreaks ofEVDinAfricaand
reportedcasefatalityratesofupto90%[6].TransmissionofEbolavirustohumansisnotyet
fullyunderstood,butislikelyduetoincidentalexposuretoinfectedanimals[7-9].EVDspreads
throughhuman-to-humantransmission,withinfectionresultingfromdirectcontactwithblood,
secretions, organs or other bodily fluids of infected people, and indirect contact with
environmentscontaminatedbysuchfluids[6].
EVD hasan incubation periodof 2 to 21 days (7 dayson average, dependingon the strain)
followed by a rapid onset of non-specific symptoms such as fever, extreme fatigue,
gastrointestinal complaints, abdominal pain, anorexia, headache, myalgias and/or arthralgias.
Theseinitialsymptomslastforabout2to7daysafterwhichmoreseveresymptomsrelatedto
hemorrhagic fever occur,including hemorrhagicrash, epistaxis, mucosalbleeding, hematuria,
hemoptysis,hematemesis,melena,conjunctivalhemorrhage,tachypnea,confusion,somnolence,
and hearing loss. Laboratory findings include low white blood cell and platelet counts and
elevated liver enzymes [6]. In general, the symptoms last for about 7 to14 days after which
recoverymayoccur.Deathcanoccur6to16daysaftertheonsetofsymptoms[7,10].People
areinfectiousaslongastheirbloodandsecretionscontainthevirus;theviruswasisolatedfrom
semen61daysafteronsetofillnessinamanwhowasinfectedinalaboratory[6].
Immunoglobulin M (IgM) antibodies to the virus appear 2 to 9 days after infection whereas
immunoglobulinG(IgG)antibodiesappearapproximately17to25daysafterinfection,which
coincideswiththerecoveryphase. Insurvivors ofEVD,bothhumoralimmunityandcellular
immunityaredetected,however,theirrelativecontributiontoprotectionisunknown[11].
WhileprioroutbreaksofEVDhavebeenlocalizedtoregionsofAfrica,thereisapotentialthreat
ofspreadtoothercountriesgiventhefrequencyofinternationaltravel.The2014outbreakin
WestAfricawasfirstrecognizedinMarch2014and,asofJune18,2014theknowncaserate
exceededthelargestpriorEVDoutbreakwhichoccurredinUgandain2000-2001with425cases
and224deaths(case-fatalityrate=53%)[12].ByMarch30,2016theWHOdeclaredanendto
the Public Health Emergency of International Concern regarding the Ebola virus disease
outbreakinWestAfrica,withacombinedtotal(laboratory-confirmed,probableandsuspected)
28,646casesand11,323deathsreported(casefatalityrate=40%)[13].Insubsequent years,
therehavebeenmultipleEbolaoutbreakswithcasesdetectedinmany countries, includingat
leastnineoutbreaksintheDemocraticRepublicoftheCongo(DRC).Theoutbreakthatstarted

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in2018intheDRChasbecomethesecondlargestafterthe2014WestAfricanoutbreakwitha
combinedtotal(laboratory-confirmedandprobable)of1,016casesand634deaths(casefatality
rate=62%)asofMarch24,2019[14].
VirusesintheFiloviridaefamilyarealsocategorizedaspotentialthreatsforuseasbiological
weaponsduetoeaseofdisseminationandtransmission,andhighlevelsofmortality.Currently,
noeffectivetherapiesorFDA-licensedvaccinesexistforanymemberofFiloviridaefamilyof
viruses.
1.2
RationalefortheEbolaSudanChimpanzeeAdenovirusVectorVaccine,VRC-
EBOADC086-00-VP(cAd3-EBOS)andRV508StudyDesign
Avaccinationstrategytoachieveimmediateprotectiveimmunityinmostrecipientswithasingle
vaccinationagainstEbolawouldbedesirableinanoutbreaksetting.Vaccinationstrategiesthat
achievedurableprotectiveimmunitywouldbedesirableforpopulationsinareasoftheworld
where outbreaks occur sporadically. Optimally, one approach would serve both needs, but a
differentapproachmaybeneededforrapidimmunitythanisneededfordurableimmunity.
The VRC/NIAID/NIH and GSK have developed and evaluated a recombinant cAd3-EBO
vaccine.Thecandidatevaccineiscomprisedoftwovectors,eachofwhichrespectivelyencodes
WTGP-onefromtheZaire(cAd3-EBOZ)andonefromtheSudanspeciesofEbola(cAd3-
EBOS).ClinicalevaluationofcAd3-EVOZwasacceleratedwiththeoccurrenceoftheWest
AfricanEbolavirusoutbreakin2014.Basedon1)cAd3-EBOvaccinesafety,immunogenicity
andprotectionstudiesinNHP,2)experiencewithotherviralvaccinesusingthecAd3expression
system, and 3)the timing of the severe Ebola outbreak in west Africa, human clinical trials
evaluatingthecAd3vectorswithboththeWTGPoftheEbolavirusZaireandoftheEbolavirus
SudanandthecAd3-EBOZonlyvaccinebeganinSeptember,2014(theVRC207study).VRC
207 and subsequent studies demonstrated both cAd3-EBO and cAd3-EBO Z were safe and
immunogenicinhumansatdosesashighas2x10^11PUIM(VRC207,RV422)[15-19].Bythe
end of 2017, greater than 500 participants will have received the cAd3-EBO Z vaccine in
ongoinginternationalstudies.
ThecAd3EbolavirusSudanvaccine,(cAd3-EBOS)VRC-EBOADV086-00-VP,whichcould
alsobeusedintheeventofanEbolaSudanoutbreak,hasnotbeenevaluatedasastand-alone
vaccinetoconfirmitssafetyandimmunogenicity.RV508willevaluatethesinglevectorcAd3
EbolavirusSudanvaccineatthesamedosesaswereevaluatedinVRC207andRV422.Because
ofthesmallamountofexistingsafetydataoncAd3-EBOSasacomponentofthecAd3-EBO
vaccine, RV 508 will evaluate the two doses of cAd3-EBO S alone in an open-label, dose-
escalationdesigntocollectmoredataonthesafetyandpreliminaryimmunogenicitythatmay
furtherdescribetheextentofcAd3-EBOS’rapidimmunitywithasingleinjection.
1.2.1
PreviousHumanExperiencewithVRCFilovirusVaccines
The VRC/NIAID/NIH has developed seven different investigational Ebola vaccines to date,
whichwerepreviouslyevaluatedinaseriesofPhaseIclinicaltrials.Thevaccineconstructswere
showntobesafe,welltoleratedandimmunogenicinhumanclinicaltrials(Table2).

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Table2:
SummaryoftheStudiesforEvaluationofVRCEbolaandMarburg
Vaccines
Study Identifier
(Clinicaltrials.gov)
StudyDesign
VaccineProduct(s)
Dosage, route,
x N administrations
Accrual
Product/Placebo
VRC204[20]
(NCT00072605)
Phase I,
randomized,
placebo-controlled,
doseescalation
VRC-EBODNA012-00-VP
(EbolaDNA,∆TMGP)
2mgIMx3doses
4mgIMx3doses
8mgIMx3doses
5/2
8/2
8/2
VRC205[21]
(NCT00374309)
Phase I,
randomized,
placebo-controlled,
dose escalation
VRC-EBOADV018-00-VP
(Ebola-rAd5,PMGP)
2x109vp†IMx1dose
2x1010vpIMx1dose
12/4
12/4
VRC206[22,23]
(NCT00605514)
Phase I,
openlabel
VRC-EBODNA023-00-VP
(EbolaDNA,WTGP)

VRC-MARDNA025-00-VP
(MarburgDNA,WTGP)
4mgIMx3or4doses


4mgIMx3or4doses
10/0


10/0
RV247[24]
(NCT00997607)
Phase Ib,
randomized,
placebo-controlled
VRC-EBODNA023-00-VP
(EbolaDNA,WTGP)

VRC-MARDNA025-00-VP
(MarburgDNA,WTGP)

VRC-EBODNA023-00-VP
(EbolaDNA,WTGP)
and
VRC-MARDNA025-00-VP
(MarburgDNA,WTGP)
4mgIMx3doses


4mgIMx3doses


4mgIMx3doses;both
vaccines
30/6


30/6


30/6

RV422
(NCT02354404)
PhaseIb,
randomized,open
label
VRC-EBOADC069-00-VP
(cAd3-EBO,WTGP)


VRC-EBOADC076-00-VP
(cAd3-EBOZ,WTGP)


VRC-EBOMVA079-00-VP
(MVA-EbolaZ)
(prime)
2x1010PUIMx1dose
2x1011PUIMx1dose

(prime)
1x1010PUIMx1dose
1x1011PUIMx1dose

(boost)
1x108PUIMx1dose
30/0
30/0



15/0
15/0


66/0
VRC207[17]
(NCT02231866)
PhaseI/Ib,
openlabel
VRC-EBOADC069-00-VP
(cAd3-EBO,WTGP)

VRC-EBOADC076-00-VP
(cAd3-EBOZ,WTGP)

FurtherevaluatecAd3-EBO
Z*
2x1010PUIMx1dose
2x1011PUIMx1dose

1x1010PUIMx1dose
1x1011PUIMx1dose
10/0
10/0

10/0
10/0

100(finalstudy
accrual–143*)

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Study Identifier
(Clinicaltrials.gov)
StudyDesign
VaccineProduct(s)
Dosage, route,
x N administrations
Accrual
Product/Placebo
VRC208
(NCT02408913)
PhaseI/Ib,open
label,dose
escalationand
rolloverstudyof
VRC207
VRC-EBOMVA079-00-VP
(MVA-EbolaZ)

VRC-EBOMVA079-00-VP
(MVA-EbolaZ)

VRC-EBOADC069-00-VP
(cAd3-EBO,WTGP)
+
VRC-EBOMVA079-00-VP
(MVA-EbolaZ)
[ReceivedinVRC207]
[VRC-EBOADC069-00-VP]
[VRC-EBOADC069-00-VP]
[VRC-EBOADC076-00-VP]
[VRC-EBOADC076-00-VP]
+

VRC-EBOMVA079-00-VP
(MVA-EbolaZ)
1x107PFU*IMx1dose


1x108PFUIMx1dose

(prime)
2x1011PUIMx1dose
+

(boost)
1x108PFUIMx1dose

(prime)
2x1010PUx1dose
2x1011PUx1dose
1x1010PUx1dose
1x1011PUx1dose
+
(boost)
1x108PFUx1dose

5/0


5/0


13/0




ongoing
(upto140)/0

MaliandMaryland[19]
(NCT02231866;
NCT02267109)
PhaseIsingleblind,
randomized;
PhaseIb,openlabel
andnesteddouble-
blind,dose
escalationofMVA-
BN®-Filo
VRC-EBOADC076-00-VP
(cAd3-EBOZ,WTGP)










VRC-EBOADC076-00-VP
(cAd3-EBOZ,WTGP)
+
MVA-BN®-Filo
(Maryland)
1x1010PUIMx1dose
1x1011PUIMx1dose

(Mali)
1x1010PUx1dose
2.5x1010PUx1dose
5x1010PUx1dose
1x1011PUx1dose

nestedstudy(from
above)
1x1010PUx1dose
2.5x1010PUx1dose
5x1010PUx1dose
1x1011PUx1dose

10/0
10/0


10/0
35/0
35/0
11/0



5/5
7/6
10/9
5/5
GSKmonovalent
ChAd3EbolaZaire[16]
(NCT02240875)
PhaseIa,openlabel,
longterm
immunology

VRC-EBOADC076-00-VP
(cAd3-EBOZ,WTGP)




(prime)
1x1010PUx1dose
2.5x1010PUx1dose
5x1010PUx1dose

(prime)
(reducedprimeboost
interval,7or14days)

20/0
20/0
20/0



8/0(7days)

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Study Identifier
(Clinicaltrials.gov)
StudyDesign
VaccineProduct(s)
Dosage, route,
x N administrations
Accrual
Product/Placebo



MVA-BN®-Filo
2.5x1010 PUx1dose


(boost)
1.5x108PUx1dose
3x108PUx1dose
8/0(14days)



34/0
12/0
GSKmonovalent
ChAd3EbolaZaire[25]
(NCT02289027)
PhaseI/IIa,double-
blind,placebo
controlled,dose
finding

VRC-EBOADC076-00-VP
(cAd3-EBOZ,WTGP)
(potentiallydeployed)
2.5x1010PUx1dose
5x1010PUx1dose

(non-deployed)
2.5x1010PUx1dose
5x1010PUx1dose

9/0
9/0


42/42/2
†viralparticles
^particleunits
*plaqueformingunits
#MVA-BN®-FiloisanMVAvaccineexpressingEbola-ZaireGP,-SudanGP,MarburgGP,andTai-ForestEbola
nucleoprotein

Eachclinicaltrialhascontributedtoproductdevelopmentandabetterunderstandingofhuman
immuneresponsestofilovirusantigens.Thefirstinvestigationalvaccinestudy,VRC204,was
initiatedin2003.Thiswasa3-plasmidrecombinantDNAvaccine,VRC-EBODNA012-00-VP,
that encoded for nucleoprotein (NP) from the Zaire strain of Ebola and for transmembrane
deleted(ΔTM)EbolaGPsequencesfrombothZaireandSudanstrains.Atthattime,deletionof
the TMregionofthe GPwasincluded inthe vaccineconstruct design toaddresstheoretical
concernsrelatedtocellulartoxicitythathad beenobservedduringinvitroexperimentswhen
plasmidsexpressingfulllength,WTGPproteinsweretransfectedintocellculture[26].
The second investigational vaccine study, VRC 205, evaluated a replication-defective,
recombinant adenovirus serotype 5 vaccine, VRC-EBOADV018-00-VP (Ebola-rAd5). The
constructsinthisvaccineencodedGPgeneswithapoint-mutation[asparticacidsubstitutedfor
glutamic acid at position 71(E71D)], which had been found to be safe and immunogenic in
animalstudies.ThevaccineinducedhumoralandTcellresponsestothepointmutantGPinserts
withasinglevaccination,butpre-existingimmunitytotheAd5viruspartiallybluntedantibody
responses to the rAd5-expressed antigen [21]. Because complete protection in macaques
vaccinatedwiththisEbola-rAdvaccineencodingforE71DGP(Z)combinedwithE71DGP(S)
wasdemonstrated,thevaccinewasfurtherevaluatedinpeople(VRC205)[27].
Non-humanprimate(NHP)studies,ongoinginparallelwiththeconductofthesehumanclinical
trials, demonstrated that ∆TM GP- and PM GP-expressed antigens were partially protective
against Ebola virusinfection, butWT GP constructsprovidedthe highest level ofprotection
[27]. Therefore, the WT GP antigen became the focus of Ebola vaccine research and
developmentatVRC/NIAID.
ThethirdinvestigationalEbolavaccinetoundergoNHPevaluation,VRC-EBODNA023-00-VP
(EbolaDNAWT),wasarecombinantDNAvaccinecomposedof2plasmids,eachencodingfor
thewildtype(WT)GPoftheZaireorSudanstrainofEbolavirus.Atthesametime,aDNA

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vaccine encoding for GP of the Angola strain of Marburgvirus, VRC-MARDNA025-00-VP
(MarburgDNA),wasevaluated.TheplasmidDNAvaccinesencodingforEbolaWTGPand
Marburg WT GP evaluated in both the VRC 206 and RV 247 studies were safe and
immunogenic butrepetitive DNA-GPvaccinationswith 3or 4doses were needed toachieve
highresponseratestosomeoftheantigens.Importantly,theevaluationofWTGPconstructshas
notbeenassociatedwithcoagulopathyorseriousadverseevents[22-24].
Asnotedabove,emergenceofthe2014EbolaepidemicrapidlyadvancedthenextEbolavirus
candidatevaccinesintotrial.ThevaccineantigenswerechosenbasedontheaboveDNAdataof
theWTGPantigensfromtheZaireandSudanstrainsofEbola.ThechimpanzeeAd3vector
(cAd3)wasselectedbecause1)ithaslittletonopre-existingimmunityinhumanpopulations,2)
itssuperiorimmunogenicityinhumans(asrAd5vectorswerenolongerbeingpursuedbyVRC)
relative toDNAvaccinesforotherviral diseases, and 3)itsperformanceinNHP Ebolavirus
challengestudies.
To further buildon theimmunogenicityof thecAd3-EBO GPcandidate vaccine,aModified
Vaccinia Ankara (MVA) Ebola vaccine has also been developed. VRC-EBOMVA079-00-VP
(MVA-EbolaZ) is also undergoing staged clinicalevaluationboth as a single IM injection at
dosesof1x107PFUand1x108PFUandasaboosttostudyparticipantswhopreviouslyreceived
cAd3-EBO(acombinationofcAd3-EBOZandEBOS)andcAd3-EBOZ(n=30,ongoing)in
VRC208as wellasin internationalstudies beingconducted byothers.To date,cAd3-EBO,
cAd3-EBOZ,andMVA-EbolaZhavebeenwelltoleratedandappearsafeforfurtherevaluation
inhumans.
1.2.2
PreviousHumanExperiencewithChimpanzeeAdenovirusVectorSerotype3
(cAd3)
Recombinantchimpanzeeadenovirusserotype3(cAd3orChAd3)isasubgroupCadenovirus
withpropertiessimilartothoseofhumanadenovirusserotype5(Ad5).BothcAd3andcAd63
vectorswereinitiallyconsideredfordevelopmentofanewEbolavirusvaccinebasedontheir
immunological properties and because the vectors had already advanced into Phase I human
clinicaltrials.Boththe cAd3 andcAd63 wereshown tobesafe andimmunogenicinhuman
studies evaluating candidate vaccines for hepatitis C virus (HCV) [28] and malaria [29],
respectively.Afterinitialconsiderationoftheseadenoviralvectors,thecAd3vectorwaschosen
for further development as a candidate vaccine because it appeared more protective against
EbolainfectionintheNHPmodel.
SerologicalstudiesshowedalowseroprevalenceinhumanseraforantibodiestocAd3[30][and
unpublishedVRCdata],andwhenpresent,antibodytitersarelow.Ad5pre-existingimmunity
didnotappeartocross-reactwithcAd3inmice[31,32][andunpublishedVRCdata].ThecAd3-
based vaccines were capable of inducing an immune response comparable to human Ad5
vectoredvaccines[31,32].VRCinvestigatorsshowedthatcAd3vectorshadsimilarlevelsof
potencyasrAd5withvariousantigensincludinginfluenzaHAandHIVEnv[unpublishedVRC
data].
InaPhaseIstudy,Barnesetal.testedtworareserotypeadenovirusvectors,cAd3andhuman
adenovirusserotype6,eachexpressingHCVantigens.Atotalof41participantswerevaccinated
byintramuscular(IM)injectionwithdosages upto7.5x1010viralparticles(vp) perinjection.

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Severalprime-boostscheduleswereevaluatedwith4-6participantspertreatmentgroup.Overall,
these vaccines were assessed as safe and well tolerated. Mostly mild, self-limited local and
systemicreactogenicitywasobservedwhichwasdose-dependentbutdidnotdiffersignificantly
between priming and boosting.The vaccinationsinducedHCV-specific immunity with broad
specificity that was sustainedfor at least1 year afterthe boost with heterologous adenoviral
vector[28].Chimpanzeeadenoviralvectortype3vaccineshavebeensafeinhealthyadultsat
dosagesupto2x1011PUperinjectionincompletedandongoingclinicaltrials[28,29].
Published data supporting evaluation of the cAd3-EBO S comes from the Phase I, dose-
escalation, open-label trial of cAd3-EBO (cAd3-EBO Z and –EBO S) performed by
Ledgerwood, et. al. [17] Twenty healthy adults, sequentially enrolled in two groups of 10,
received IM dosesof2×1010 particle units or2×1011 particle units. Nosafety concerns were
identified,althoughtransientfeverdevelopedwithin1dayaftervaccinationintwoparticipants
in the high dose group. Glycoprotein-specific antibodies were induced in all 20 participants,
howeverthehighdosegroupdevelopedantibodiesofhighermagnitudeandmorefrequentCD4
andCD8Tcellresponsestovaccineantigen.Theantibodylevelsofthehighdosegroupwerein
therangeassociatedwithvaccine-inducedprotectiveimmunityinNHPchallengestudies,and
theantibodyresponsesweresustainedtoweek48.OtherstudiesofcAd3-EBOandcAd3-EBOZ
inU.S.,SwissandMalianadultsshowedthevaccinestobesafeandimmunogenic[16,17,19,
25].EquivalentcAd3EbolaSudanWTGPdoseswillbetestedinthisslowlyenrolling,staged,
dose-escalationstudy.
It has been noted the 2x1011 PU dose of cAd3-EBO vaccine was associated with more
reactogenicity than the 2x1010 PU dose, and the pattern is similar to other adenoviral vector
vaccines.Thefirstsetsofclinicaldatasuggestthatabout70%ofparticipantswillhaveatleast
onesystemicreactogenicitysymptom.Reactogenicitytypicallyoccursonthedayofordayafter
vaccination and may include headache, malaise, myalgia, with a smaller percentage also
experiencingfeverorchills.Whenpresent,feveronsetwaswithinonedayofvaccinationand
resolved within 24 hours of onset. A pattern of fever, occurring later than one day after
vaccinationorlastinglongerthanaday,mayrequireevaluationforadditionaletiology[33].
1.3
PreclinicalStudiesSupportingtheSafetyofVRC-EBOADC086-00-VP(cAd3-EBO
S)
Prior to evaluation as an Ebola antigen vector, cAd3 underwent nonclinical toxicology
evaluations as both an investigational HCV vaccine product, AdCh3-HCV (BB-IND 14818,
Okairos, Inc.) and an investigational HIV vaccine product, VRC-HIVADC064-00-VP. In
addition, DNAplasmidvaccines expressingthe EbolavirusZaireor theSudan DNA WTGP
antigenshavebeenevaluatedinbothaGLPtoxicitystudyandtwoPhaseIclinicaltrials(BB-
IND 13609, RCHSPB). The March 2014 Ebola outbreak in West Africa [34] prompted the
VRC/NIAIDtoaccelerateevaluationofVRC-cAd3-EBO[EBOADC069-00-VP–amixoftwo
vectors - one expressing the WT GP Zaire and one expressing the WT GP Sudan]; and the
VRC/NIAID proposed to the FDA that the prior, related nonclinical and clinical studies
(AdCH3-HCV,cAd3-HIV,EbolaDNAWTGP)supportedevaluationofthecAd3-EBOvaccine
throughastaged,doseescalationPhaseIstudydesignwithouttheconductofaGLPtoxicity
study. The FDA concurred and no preclinical GLP toxicology study was performed prior to
phaseIinitiation.TheVRC/NIAIDwithitscollaboratingresearchersthensoughtandreceived
approvaltoevaluatethecAd3EBOWTGPZairevaccinealoneasavaccineunderthesame

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IND.ThiswasdesignatedVRC-EBOADC076-00-VP(cAd3-EBOZ).Thecurrentproposalis
nowtore-evaluatetheothercomponentofcAd3-EBO,cAd3-EBOSasaseparatevaccinewith
thesamestaged,doseescalationPhaseIstudydesign.
1.4
NonclinicalImmunogenicityandProtectionStudiesofcAd3Constructs
Several non-GLP studies were performed in cynomolgus macaques to select the cAd3-based
EBOconstructsforfurtherdevelopmentandtoprovideanimalproof-of-conceptdatabeforethe
Phase I clinical studies. Research-grade materials, made with the same constructs as clinical
material,of1)cAd3EBOZ(containingGPfromEbolavirusZaire),2)cAd3EBOS(containing
WTGPfromEbolavirusSudan),3)cAd3-EBO(composedofa1:1ratioofcAd3EBOZand
cAd3EBOS)[18]wereusedinallrespectiveviralchallengestudiessummarizedbelowinTable
3.
Table3.
PreclinicalProof-of-ConceptStudiesinCynomolgusMacaques
Study Purpose
Study Outcome
Demonstrateprotectionagainstlethalchallenge
withEbolavirusZaireincynomolgusmacaques
aftersingleIMdoseofcAd3-EBOZ
100%protectionafterasingleIMdoseof
cAd3-EBOZat1010and1011VP
Demonstrate protection against lethal challenge
withEbolavirusZaireincynomolgusmacaques
aftersingleIMdoseofcAd3-EBO
100% protection after a single IM dose of
cAd3-EBOat2x1010VP

50%protectionaftercAd3-EBOat2x109VP
Demonstrateprotectionagainstlethalchallenge
withEbolavirusSudanincynomolgusmacaques
aftersingleIMdoseofcAd3-EBO
100%protectionagainstEbolavirusSudan
afterasingleIMdoseofcAd3-EBOat
2x1010VP
Demonstrate generation of humoral and cellular
immuneresponsesaftersingleIMdoseofcAd3-
EBOat2x109or2x1010VP
Single IM dose of cAd3-EBO at 2x109VP or
2x1010VPelicitedantibodyandantigen-
specificCD4+andCD8+Tcellresponses.
Thelowercellularimmuneresponses
correlatedwiththelowerlevelofprotection
(50%)observedafterthe2x109VPdose.
Demonstrate durability of the immune responses
aftersingleIMdoseofcAd3-EBOZat1011VP
orcAd3-EBOat2x1010VPadministered10
monthsbeforethelethalchallengewith
EbolavirusZaire.
Protective immune responses measured
duringtheacutephaseofinfectiondeclined
overtime.Whenchallenged10monthsafter
vaccination,2/4macaqueswereprotected
afterasingleIMdoseofcAd3-EBOZat
1011VPwhile0/4wereprotectedaftera
singleIMdoseofcAd3-EBOat2x1010VP.

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Demonstrateprotectionagainstlethalchallenge
withEbolavirusZaireincynomolgusmacaques
afterprimewithsingleIMdoseofcAd3-EBO
andweek8boostwithsingleIMdoseofMVA
(expressingGPsfromEBOVandSUDV)
100%protectionafteraprimewithasingle
IMdoseofcAd3-EBOat1010VPandweek
8boostwithasingleIMdoseofMVA
(expressingGPsfromEBOVandSUDV)at
108PFU**
Demonstrateimmunogenicityandprotection
againstlethalIMoraerosolchallengewith
EbolavirusSudanincynomolgusmacaquesafter
singleIMdoseofcAd3-EBOS
100%protectionagainstIMchallengewith
EbolavirusSudanafterasingleIMdoseof
cAd3-EBOSat1010VP;4of5animals
survivedaerosolchallengeafterasingleIM
doseofcAd3-EBOSat1010VP.Pre-
challengeplasmaanti-GPtiterswere
comparableinbothgroupsofanimals.
*VP– ViralParticles
**PFU–Plaqueformingunits=Ameasureofthequantityofindividualinfectiousparticles(e.g.virusparticles)
basedonthenumberofplaqueformedperunitvolume.

1.5
DoseJustificationforcAd3-EBOS
QuantificationofthevaccineisbasedoncAd3particleunits(PU).ThecAd3-EBOSvaccine
willbeevaluatedinhumansat1x1010PUand1x1011PUdoses.Thesedoseswereselectedbased
onagoodsafetyprofile,easeofadministration,andreliableimmunogenicityfromdatacollected
in non-human primate studies. In addition, the doses were shown to provide partial to full
protection in the accepted challenge model. Doses between 1x1010 PU and 1x1011 PU
demonstratedEbola-SudanGP-elicitedimmunogenicitywasalsocomparabletothatseentothe
Ebola-ZaireandMarburgGPantigenswhenexpressedbythesamecAd3vector.Thedosesof
cAd3vectorproposedforthisstudy,whenexpressingavarietyofviralinserts,havealsobeen
demonstratedtobesafeinhumans.PleaserefertotheIBforadditionaldetails.

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2.0
STUDYOBJECTIVES
2.1
PrimaryObjectives
· ToevaluatethesafetyandtolerabilityofVRC-EBOADC086-00-VPwhenadministered
IMatadoseof1x1010particleunits(PU)tohealthyadults;
· ToevaluatethesafetyandtolerabilityofVRC-EBOADC086-00-VPwhenadministered
IMatadoseof1x1011PUtohealthyadults.
2.2
SecondaryObjectives
· ToevaluatetheantibodyresponsetotheGPinsertandthecAd3vectorinVRC-
EBOADC086-00-VPat4weeksaftervaccinationasassessedbyGPELISAandvector-
specificneutralizationassays,respectively.
· ToevaluatetheEbolaSudanGP-specificTcellresponsesinVRC-EBOADC086-00-VP
at4weeksaftervaccinationasassessedbyICS.
2.3
ExploratoryObjectives
· ToevaluatetheimmunogenicityofVRC-EBOADC086-00-VPbyvariousassaymethods
atsomeoralloftheresearchsamplecollectiontimepointsindicatedintheSOE;genetic
factorsassociatedwithimmuneresponsemayalsobeevaluated.
· Toevaluatevaccine-inducedmRNAexpressionprofilesthroughStudyWeek1.
· ToevaluatethetimecourseanddurabilityofcAd3neutralizingantibodytiters,mediators
ofinflammationfollowingvaccinationandtimecourseanddurabilityofimmune
responsebyavarietyofexploratoryassaysusingsamplescollectedthroughoutthestudy.
· ToisolateMAbstodetermineepitopespecificityandtheirfunctionalcapacity.

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3.0
ENDPOINTS
3.1
PrimaryEndpoints:Safety
Assessment of product safety will include clinical observation and monitoring of clinical
chemistry and hematology parameters. Safety will be closely monitored after injection and
evaluatedthrough48weeksafterthestudyinjection.Thefollowingparameterswillbeassessed:
· Occurrenceofsolicitedlocalreactogenicitysignsandsymptomsfor7daysfollowingthe
vaccination
· Occurrenceofsolicitedsystemicreactogenicitysignsandsymptomsfor7daysfollowingthe
vaccination
· Changefrombaselineforsafetylaboratorymeasures
· Occurrenceofadverseeventsofallseveritiesthrough28daysafterthestudyinjection
· Occurrenceofseriousadverseeventsandnewchronicmedicalconditionsthroughthelast
studyvisit
3.2
SecondaryEndpoints:Immunogenicity
Antibody titers, response rates andmagnitudes willbe the immunogenicity endpointsforthe
followingassayswhererelevant:ELISAandneutralizationantigen-specificassaysforantibody
responsesandICSassaysforTcellresponses.Theprincipaltimepointforassessingantibody
andTcellresponsesisWeek4aftervaccination.
3.3
ExploratoryEndpoints
ELISpot assays to assess T and B cell responses will be performed with research samples
collectedatstudytimepointsshownintheSOE(Appendix1),aswellasevaluationofgenetic
factors associated with immune responses and time courses of immune responses (i.e. AUC
evaluation) may be completed as exploratory evaluations. MAbs may be isolated from
cryopreservedperipheralbloodmononuclearcells(PBMC)andevaluatedtodetermineamong
other characteristics, epitope specificity, and functional capacity. Vaccine-induced mRNA
expressionprofilesthrough1weekaftervaccinationmayalsobeperformedasanexploratory
evaluation. Plasmablasts will be isolated from whole blood at day 7 to evaluate immediate
developmentofantibodiestoEbolaGP.

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4.0
STUDYDESIGNANDPOPULATION
ThisisaPhaseIopen-label,dose-escalationclinicaltrialtoevaluatethesafety,tolerabilityand
immunogenicityofarecombinantvectorfortheSudanstrainoftheEbolavirus.Thisstudywill
beconductedattheMUWRPinKampala,Uganda.
Atotalof40healthyadults,20ineachdosagegroup,willreceiveasinglevaccineinjectionof
cAd3-EBOSat1x1011PU/mLor1x1010PU/mL.Thestudywillbeginwithenrollmentof3
participantsintoGroup1.Afteratleast7daysoffollow-upforthefirst3vaccinatedparticipants,
aninterimsafetyreviewwilloccurbeforeenrollmentofadditionalparticipantsintothegroup.If
nosafetyissuesareidentified,anadditional17participantswillbeenrolledtocompleteGroup1.
When there is a minimum of seven days of follow-up safety data from the last enrolled
participantinGroup1,aninterimsafetyreviewwilloccur.Oncenosafetyissuesareidentified,
enrollment of participants into the next dose level will begin with the enrollment of 3
participants.Afteratleast7daysoffollow-upforthefirst3vaccinatedparticipantsinGroup2,
aninterimsafetyreviewwilloccurbeforeenrollmentofadditionalparticipantsintoGroup2.If
nosafetyissuesareidentified,anadditional17participantswillbeenrolledtocompleteGroup2.
Forthefirst3participantsineachgroup,onlyoneparticipantperdaywillbeenrolled.Thestudy
groupsandvaccinationschemaisshowninTable1.
StudyagentadministrationwillbeonDay0.Thestudyincludesdailyreviewofanynewsafety
databyastudyclinicianandweeklyreviewofsafetydatabytheProtocolSafetyReviewTeam
(PSRT).Thestagedenrollmentplanandplanforinterimsafetyreviews(Section7.3)appliesto
bothGroup1andGroup2.TheinterimsafetyreviewswillbeconductedbythePSRT.
4.1
Eligibility
Screeningforeligiblevolunteerswillbeperformedwithin8weeksbeforethefirstadministration
ofstudyvaccineatWeek0.Studyparticipantsmustbehealthy(onthebasisofmedicalhistory,
physical examination, vital signs measurement, and laboratory assessments), adult men and
women,aged18to50years.
4.1.1
InclusionCriteria
Avolunteermustmeetallofthefollowingcriteria:
1. 18to50yearsold.
2. Availableforclinicalfollow-upthroughWeek48afterenrollment.
3. Abletoprovideproofofidentitytothesatisfactionofthestudycliniciancompleting
theenrollmentprocess.
4. Ableandwillingtoprovidefingerprintsandhavetheirphotographstakenincluding
injectionsitephotographs.
5. Mustallowhomevisits
6. MustcompleteanAssessmentofUnderstanding(AoU)priortoenrollmentby
answering9outof10questionsatleastoncein3attempts.

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7. Abletoread(EnglishorLuganda)andwillingtocompletetheinformedconsent
process.
8. Ingoodgeneralhealthwithoutclinicallysignificantmedicalhistory.
9. Physicalexaminationandlaboratoryresultswithoutclinicallysignificantfindingsanda
bodymassindex(BMI)≤40withinthe56dayspriortoenrollment.
LaboratoryCriteriawithin56dayspriortoenrollment:
10.Hemoglobin≥11.0g/dLforwomen;≥12.5g/dLformen.
11.Whitebloodcells(WBC)=2,500-12,000cells/mm3.
12.Totallymphocytecount≥800cells/mm3.
13.Platelets=125,000–400,000/mm3.
14.Alanineaminotransferase(ALT)≤1.25xupperlimitofnormal.
15.Serumcreatinine≤1xupperlimitofnormal.
16.HIV-uninfectedasevidencedbyanegativeHIVdiagnostictest.
Female-SpecificCriteria:
17.Negativeβ-HCG(humanchorionicgonadotropin)pregnancytest;serumβ-HCGat
screeningandurineβ-HCGatenrollmentifwomanisofreproductivepotential.
18.Agreestouseaneffectivemeansofbirthcontrolfromatleast21dayspriorto
enrollmentthrough24weeksafterstudyvaccinationifassessedtobeofreproductive
potential.
4.1.2
ExclusionCriteria
Avolunteerwillbeexcludedifoneormoreofthefollowingconditionsapply:
Volunteerhasreceivedanyofthefollowingsubstances:
1. InvestigationalEbolaorMarburgvaccineinapriorclinicaltrialorpriorreceiptofa
cAd3adenoviralvectoredinvestigationalvaccine.
2. Chronicuseofimmunomodulatorsandsystemicglucocorticoidsindailydosesof
glucocorticoidequivalence>20mgofprednisolone,forperiodsexceeding10days.
Non-steroidalanti-inflammatorydrugs[NSAIDS]arepermitted.Participantsthathave
usedlessthanthestatedglucocorticoiddosemaystillbeexcludedattheInvestigator’s
discretion.
3. Bloodproductswithin112days(16weeks)priortoenrollment.
4. Investigationalresearchagentswithin28days(4weeks)priortoenrollment.

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5. Liveattenuatedvaccineswithin28days(4weeks)priortoenrollment.
6. Subunitorkilledvaccineswithin14days(2weeks)priortoenrollment.
7. Currentanti-tuberculosisprophylaxisortherapy.
Female-specificcriteria:
8. Womanwhoispregnant,breast-feedingorplanningtobecomepregnantduringthefirst
24weeksafterstudyvaccineadministration.
Volunteerhasahistoryofanyofthefollowingclinicallysignificantconditions:
9. Seriousadversereactionstovaccinessuchasanaphylaxis,urticaria(hives),respiratory
difficulty,angioedema,orabdominalpain.
10.Allergicreactiontoexcipientsinthestudyvaccineincludinggentamycin,neomycinor
streptomycin.
11.Clinicallysignificantautoimmunediseaseorimmunodeficiency.
12.Asthmathatisnotwellcontrolled.
13.PositiveresultonanRPRtest.
14.Diabetesmellitus(typeIorII).
15.Thyroiddiseasethatisnotwellcontrolled.
16.Ahistoryofhereditaryangioedema(HAE),acquiredangioedema(AAE),oridiopathic
formsofangioedema.
17.Idiopathicurticariawithinthelast1year.
18.Hypertensionthatisnotwellcontrolled.
19.Bleedingdisorderdiagnosedbyadoctor(e.g.factordeficiency,coagulopathy,or
plateletdisorderrequiringspecialprecautions)orsignificantbruisingorbleeding
difficultieswithIMinjectionsorblooddraws.
20.Amalignancythatisactive,currentlybeingtreated,ornotsurgicallycured.
21.Seizureinthepast3yearsortreatmentforseizuredisorderinthepast3years.
22.Aspleniaorfunctionalasplenia.
23.Psychiatricconditionthatprecludescompliancewiththeprotocol;pastorpresent
psychoses;orwithinfiveyearspriortoenrollment,historyofasuicideplanorattempt.

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24.Anymedical,psychiatric,socialcondition,occupationalreasonorotherresponsibility
that,inthejudgmentoftheinvestigator,isacontraindicationtoprotocolparticipation
orimpairsavolunteer’sabilitytogiveinformedconsent.

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5.0
STUDYPROCEDURES
5.1
ScheduleofEvaluations
Evaluationofthesafetyofthisvaccinewillincludelaboratorystudies,medicalhistory,physical
assessmentby clinicians,andparticipantself-assessmentrecordedon a 7-daydiarycard. The
scheduleofevaluationislocatedinAppendix1.Totalbloodvolumedrawnfromeachparticipant
willnotexceed450mLinany3-monthperiod.
5.2
Recruitment,Consent,ScreeningandEnrollment
Participants will be recruited through IRB-approved recruitment materials (to include flyers,
posters,newspaperadsandradioscripts).Volunteersinterestedinthestudywillbeinvitedand
scheduledtoabriefingsessionattheirconvenience.Briefingsessionswillbeconductedbythe
PrincipalInvestigator(PI)ordesigneeattheMUWRPfacilityatregularintervalsthroughoutthe
recruitmentphase.Thebriefingsessionwillbefollowedbyanopportunityforquestionsfrom
the volunteers. All volunteers interested in this study will subsequently, individually be
administeredinformedconsent.
5.2.1
ConsentProceduresandScreening
ThePIortheirdesigneewillreviewtheconsentformindetailwithpotentialparticipantsand
answeranyquestions.Writteninformedconsentwillbeobtainedfromeachparticipantbefore
any study procedures are performed. All informed consent forms will be administered
individually,inaprivatesetting,withstrictrespectofconfidentiality.Participantswillbegiven
ample time and opportunity to inquire about details of the study, discuss with close family
membersorfriendsandaskanyquestionsbeforedatingandsigningtheconsentforms.Acopy
ofthesignedinformedconsentformwillbegiventotheparticipantalongwithacopyofthe
volunteereventschedule(Appendix3).Theconsentingprocesswillbedocumentedinthecase
reportforms(CRFs).
After providing signed informed consent the volunteer will complete an Assessment of
Understanding (AoU). Volunteers areallowed to takethe AOUthree times, butmust havea
passingscoreof90%orgreaterbythethirdattempttoparticipateinthestudy.Ifafter3attempts
topasstheAOUthevolunteerisunabletodoso,thevolunteerwillbecomeineligibleforstudy
participation.
VolunteerswhohavepassedtheAoUandhavegivenwritteninformedconsentwillundergoa
complete medical history, physical examination, and screening laboratory assessments to
determine eligibility for trial participation. The following screening assessments will be
completedaftertheinformedconsentprocesshasbeencompleted:
· Medicalhistory
· Physicalexam
· Vitalsignsandweight
· Serumpregnancytestforallfemales
· CBCwithtotallymphocytecount
· Creatinine
· ALT

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· HIVtesting(includingpre/post-testcounseling),andreferralasappropriate
· Syphilisserologytesting
· Pre-existingvectorimmunitytesting
· Peripheralbloodmononuclearcells(PBMC)andplasmaforstorage
Screeningevaluationsforspecificeligibilitycriteriamustbecompletedwithinthescreeningvisit
windowspecified(Appendix1)priortoenrollment,butmayberepeatedone timewithinthe
screeningvisitwindow,iftheinitiallaboratoryresultisnotdeemedmedicallysignificantinthe
clinicaljudgmentoftheinvestigator,inordertoconfirmeligibility.Counselingonthepotential
risksofbecomingpregnantduringthistrialwillbeprovided.Pre-HIVtestcounselingandpost-
HIVtestcounselingwillbeprovidedduringthescreeningprocess.
StudyvolunteersmaybescheduledforasecondScreeningVisittoevaluatelaboratoryandtest
resultsifanabnormalityorillnesshadbeenidentifiedatthefirstscreening.Thisapproachwill
allowstudystafftoevaluatetherecoveryfromanyillnessidentifiedatthefirstscreeningaswell
as to repeat screening laboratory tests that were abnormal at the first screen due to transient
illness.
ThePIorInvestigatoratthesitemaydiscoveranillnessorcondition,whichrequirestreatment
forthevolunteer.ThesitewillprovidebasiccareandtreatmentasperNationalguidelinesand
referthesesubjectstoanappropriatehealthcarefacilityforfurtherevaluationandtreatment.
Eligible and willing volunteers will be scheduled for an appointment for enrollment and the
initialvaccinationvisitwithin56daysofhavingsatisfiedeligibilityrequirements.
5.2.2
Day0ThroughWeek48
Day 0 is defined as the day of enrollment and study injection. Study eligibility criteria are
reviewedonDay0aspartoftheenrollmentprocess.IfclinicalassessmentonDay0suggests
significantchangesmayhaveoccurredsincethescreeningvisit,thenthephysicalexamination,
hematology tests, and blood chemistries done at screening must be repeated, as appropriate,
before the participant can receive a study vaccination. Pregnancy test results for women of
childbearing potential must be obtained prior to the study injection. Day 0 evaluations
immediatelypriortothefirstinjectionarethebaselineforsubsequentsafetyassessments.
RefertothetableinAppendix1fordetailsontheScheduleofEvaluationsandthewindow(s)
permitted. After Day 0, deviations from the visit windows in completing study visits are
discouragedandwillberecordedasprotocoldeviations,butarepermitted,atthediscretionof
the PI (or designee),in consultation with the sponsor, inthe interest of obtainingparticipant
safetyandimmunogenicityevaluationsfollowingexposuretotheinvestigationalvaccine.
StudyvisitproceduresandteststhroughWeek48includethefollowingasindicatedintheSOE
(Appendix1):
1. Signatureofstudyparticipationinformedconsentform
2. AOU(priortoenrollment)
3. Clinicalevaluations:vitalsigns;targetedphysicalexaminationonanyvisitifindicated
byinterimcomplaintsorlaboratoryfindings
4. Interimmedicalhistory,includinganynewmedicationstaken

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5. Counselingonavoidanceofpregnancy
6. Post-injectionvitalsignsandassessmentofinjectionsiteat30to60minutespost-
injection(withtargetof30to45minutes,whenpossible)
7. DiaryCard:Intheeveningonthedayofinjection;7-daysforself-assessmentby
participant
8. Urinepregnancytestforfemalesofreproductivepotential
9. CBC,totallymphocytecount,plateletcounts
10.BloodcreatinineandALT
11.HLAType
12.Serum,PBMCs,andplasmaforprotocolassessments,includingintracellularRNAand
archiving
Stored samples with consent for genetic testing may be used to elucidate genetic factors
associatedwithimmuneresponsetoavaccineandtofurtherevaluateresponsestothevaccine.
Resultsfromgenetictestingwillnotbeprovidedtoparticipantsastheresultsarenotvalidated
for clinical use. Any remainingcells, serum,orplasma will bestored at the NIAID Vaccine
ImmunologyProgram(VIP)forfutureexploratoryvirologicalandimmunologicalassaysasper
individualparticipant’sconsentforfutureuse.
5.3
AdministrationoftheStudyInjectionandOn-StudyAssessments
InjectionswillbeadministeredIMina1mLvolumebyneedleandsyringe.Itisrecommended,
butnotrequired,thattheinjectionbeadministeredintothenon-dominantarm.Whenchoosing
anarmfortheinjection, cliniciansshouldconsiderwhetherthereisanarminjury,localskin
problem or significant tattoo that precludes administering the injection or will interfere with
evaluatingthearmafterinjection.
Followingthestudyinjection,participantswillbeobservedforaminimumof30minutes.Vital
signs (temperature, blood pressure, and pulse) will be taken 30 to 60 minutes post-injection
(targetof30to45minutes).Theinjectionsitewillbeinspectedforevidenceoflocalreaction
duringthisperiod.Inkeepingwithgoodmedicalpractice,acutemedicalcarewillbeprovidedto
participantsforanyimmediateallergicreactionsorotherinjuryresultingfromparticipationin
thisresearchstudy.
5.3.1
7-DaySolicitedReactogenicity
Temperatureandsolicitedlocalandsystemicsigns/symptomswillberecordedintheclinicprior
tovaccinationandataminimumof30minutespostinjectionandthendailybytheparticipant
for7days.
Participantswillbegivena“DiaryCard”,athermometer,andaruler.Thediarycardwillbeused
asamemoryaid,onwhichtheparticipantwillrecordtemperature,localandsystemicsymptoms
andconcomitantmedicationsdailyfor7daysaftertheinjection.Participantswillbetrainedto
completethepaperdiarycard,howtousethethermometer,andhowtomeasureinjectionsite
swelling and redness using the ruler. Completion of the diary card training will be noted in
sourcedocuments.Thewritten(paper)diarycardwillbetranscribedintothestudydatabaseand
willbestoredintheparticipantfileformonitoringpurposes.

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The solicited signs and symptoms on the diary card (among others) will include: joint pain,
malaise(feelingunwell),myalgias(musclesachesotherthanatinjectionsite),headache,chills,
nausea, and pain at injection site. Where multiple assessments are taken on the same day,
participantswillberequestedtorecordtheday’shighestmeasuredtemperatureandmeasurement
oflargestdiameterforrednessandswellingattheinjectionsite.Thecompleteddiarycardsare
collectedatthefirstvisitfollowingcompletionofthe7-daydiarycard(about2weeksafterthe
injection).
Follow-uponparticipantwell-beingwillbeperformedbytelephoneorclinicvisitontheday
followingvaccinationandbyclinicvisitonDay3followingtheinjectiontoassesstheirclinical
status. Participants may call or come to the clinic at any time-point for evaluation, if they
experienceunusual,moderateorseveresignsandsymptoms.Diarycardswillbereviewedwith
the clinician at any visit from day of vaccination through the first study visit following
completion of the diary card. If upon reviewing the clinician finds that general symptom or
injectionsitesymptominformation(exceptswellingorrednessmeasurements)ismissingfrom
thediarycards,theparticipantwillbeaskedtoprovidethemissinginformationtothebestof
theirrecollection.
Ateveryvisitthroughstudyday28,allparticipantswillbeaskedabout otherinterimadverse
experiences,whichwill berecordedin sourcedocumentsandenteredintothestudydatabase
within3businessdays.Afterstudyday28,onlyseriousadverseeventsandnewchronicmedical
conditionsthatrequireongoingmedicalmanagementwillberecordedinsourcedocumentsand
enteredintothedatabase,throughthelaststudyvisit.Allotheradverseeventswillberecorded
onsourcedocumentsonly.ThePIordesigneewillassesstherelationshipofthestudyproductto
theevents.
5.3.2
ManagementofReactogenicityAdverseEventsFollowingStudyVaccinations
Participantswillbeinformedthatafeverof38.5˚C(Grade2)orhigherlastinggreaterthan24
hours, rash,urticaria,or significant impairment in theactivitiesofdaily living(ADL)should
promptavisittotheclinic.Feverlessthan38.5˚Corlastinglessthan24hoursmayprompta
clinicvisitatthediscretionofthestudyclinicians.Anyconditionwhichinthejudgmentofthe
clinicianshouldbeevaluatedclinicallyorbylaboratorytestingwouldrequireaclinicalvisit.
Participantsarepermittedtoinitiateanunscheduledclinicvisitattheirdiscretionbutthesevisits
willbecompensatedasperSection10.5.
5.3.3
ManagementofLaboratoryAbnormalitiesAfterVaccination
If any lab result is a Grade 3 or Grade 4, then repeat testing of the abnormal test will be
performedwithin48hours.ThespecifictimingofrepeattestingforaGrade2laboratorytest
changewillbedeterminedbythestudycliniciansasmedicallyappropriate.
5.4
ConcomitantMedications
Currentconcomitantmedicationsarerecordedinthestudydatabaseatenrollmentandfor7days
post-vaccination.Subsequently,concomitantmedicationswillbeupdatedinthestudydatabaseif
thereisanoccurrenceofanadverseeventthatisconsideredrelatedtotheIPorthatrequires
expeditedreportingordevelopmentofanewchronicmedicalconditionthatrequiresongoing
medicalmanagement.

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CliniciansshoulddiscusswithstudyparticipantswithregardtothetimingofFDAorlocally-
approvedvaccines.Receiptofalicensedvaccineduringstudyparticipationwillberecordedin
thestudydatabase.Otherwise,arecordofotherconcomitantmedicationchangesthroughoutthe
studywillnotberecordedinthestudydatabase.
5.5
StudyDiscontinuation
Thestudymaybestoppedorcancelledatanytimebydecision ofthePI,WalterReedArmy
Institute of Research (WRAIR) IRB, the United States Army Medical Research and
Development Command’s (USAMRDC) Office of Research Protections (ORP), Human
ResearchProtectionOffice(HRPO),NIAID,theU.S.FDA,U.S.DoD,theOfficeforHuman
Research Protection (OHRP), Uganda National Drug Authority (NDA), Uganda National
Council of Science and Technology (UNCST), or the Makerere University School of Public
Health(MUSPH)IRB.ThePIwillnotifytheIRBinwritingofanystoppageorcancellationof
thestudy.
5.5.1
EarlyDiscontinuationorWithdrawalofStudyParticipants
Aparticipantwillbetakenoutofthestudyentirelyunderthefollowingcircumstances:
· Repeatedfailuretocomplywithprotocolrequirements
· Participantrequestswithdrawal
· Participant develops amedical conditionthatis acontraindicationtocontinuing study
participation
· ThePIassessesthatitisnotinthebestinterestoftheparticipanttocontinueparticipation
inthestudy
Eachparticipanthastherighttowithdrawfromthestudyatany timeforanyreasonwithout
affectingtherighttotreatmentbytheinvestigator.Theinvestigatorshouldmakeanattemptto
contact participants who did not return for scheduled visits or follow-up. Although the
participantisnotobligedtogivereason(s)forwithdrawingprematurely,theinvestigatorshould
makeareasonableefforttoascertainthereason(s)whilefullyrespectingtheparticipant’srights.
Anyparticipantwhowithdrawsconsentwillnothaveanyfurtherdatacollectedafterconsenthas
been withdrawn. However, samples and data that were collected prior to a participant’s
withdrawalofconsentwillbeused/includedinsampleanddataanalysis.
Ifaparticipantwithdrawsfromthestudypriortoreceivingthestudyinjection,thenextavailable
participantwillbeplacedinthevacatedslot.Participantswhowithdrawpriortoreceivingthe
studyinjectionwillnotcounttowardthetotalparticipantsenrolledinthestudy.Replacements
for participants who withdraw from the study after receiving the study injection are not
permitted.
5.6
ManagementofParticipantsWhoBecomePregnant
Pregnantwomenandwomenwhoplantobecomepregnantduringthefirst24weeksafterstudy
vaccineadministrationareexcludedfromenrollment.Ifaparticipantbecomespregnantduring

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thecourseofthestudy,theywillcontinuetobefollowedfortheremainderofthestudyperiod
perprotocolSOE;however,forallsubsequentstudyvisits,blooddrawswillbelimitedtosafety
testsonly(samplesforresearchimmunologywillnotbedrawn).Fullblooddrawscanresume
post-pregnancyorpost-abortiononlyifdeemedsafefortheparticipant,pertheclinicaljudgment
of the PI in consultation with the IND Medical Officer. The PI or designated AI will be
responsibleforreportinganypregnancy.Newpregnancieswillbereviewedweeklyinaggregate
withothersafetydataandforwardedasnecessarytoIRBsandstudysponsors.
Ifaparticipantbecomespregnantwithin24weeksafterthestudyvaccination,everyeffortwill
bemadetoremainincontactwiththepregnantparticipanttorecordtheoutcomeofpregnancy
forthestudydatabase.PregnancyoutcomeswillberecordedviaastandardizedpregnancyCRF.
Informationdocumentedonthisformwillincludedateoflastmenstrualperiod,datepregnancy
confirmed,historyofcomplicationsduringpriorpregnancies(suchascongenitalabnormalities
or spontaneous abortions). A separate pregnancy outcome CRF will be completed for the
outcome of the pregnancy including date of termination or delivery, any complications of
pregnancy,thegender,weight,presenceofanycongenitalabnormalities,APGARscore,other
complicationsofdeliveryandthestatusofthechild.
Reportingoutcomesofpregnanciesthatbeginlaterthan24weeksisnotrequiredbytheIND
Sponsor,noristhereanINDSponsorrequirementforannualevaluationrequirementforchildren
borntovaccinerecipients. However,allchildrenconceived within24weeks post-vaccination
and born tovaccine recipients will beannually evaluated for a minimum of2 yearsto meet
requirementssetbyregulatoryauthoritiesinUganda.Afterterminationofthestudy,thesitewill
besolelyresponsibleformaintainingandreportingapplicabledataobtainedinthislong-term
follow-up.
5.7
ManagementofParticipantsWhoBecomeIncarcerated
Participationofprisonersisnotplannedandanyparticipantwillbesuspendedfromstudyvisits
while incarcerated, except visits or telephone contact for the purpose of ensuring participant
safety. The IRB will be notified of the period of incarceration and safety assessments to be
conducted.Dataandsamplesthatwerecollectedbeforetheperiodofincarcerationmaystillbe
storedandusedforanalyses.Afterreleasefromincarceration,theparticipantmayeitherreturnto
participationinstudyvisitsaccordingtotheSOEorstudyparticipationmaybeterminatedatthe
discretionofthePI.
Participants who have returned to the clinic after a period of incarceration of more than 12
monthswillreviewpertinentsectionsoftheconsentformwithastudystaff.Anotetotheeffect
thatthereviewwasdonewillbewrittenintheprogressnotesintheparticipant'sbinder.
5.8
ManagementandCounselingofParticipantswithPositiveHIVorSyphilisTest
Participants found to be infected with HIV or syphilis at screening will be counseled
appropriatelybyastudyphysician/nurseandreferredtoalocal healthcarefacilityforcareor
treatment.

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PHARMACYANDVACCINEADMINISTRATIONPROCEDURES
Study treatment is defined as VRC-EBOADC086-00-VP (cAd3-EBO S). Refer to the
Investigator’sBrochureforfurtherinformationaboutthestudyagent.
6.1
Regimens
FortyhealthyadultvolunteersintheKampalaarea,ages18-50years,willbeenrolledintooneof
twogroupsof20participantseachasshowninTable1.ParticipantsinGroup1willreceivea
single injection IM of cAd3-EBOSat 1x1010PUand participantsin Group 2willreceivea
singleinjectionofcAd3-EBOSat1x1011PU.
6.2
StudyProductFormulation,Preparation,andStorage
6.2.1
Formulation
ThedrugsubstancewasmanufacturedbyAdventS.r.l.(Pomezia,Italy,asubsidiaryofOkarios,
Inc.)andthevaccine,VRC-EBOADC086-00-VP(cAd3-EBOS)anddiluentweremanufactured
at the VRC Pilot Plant (VPP) operated by the Vaccine Clinical Materials Program (VCMP),
LeidosBiomedicalResearchInc.,Frederick,MD(formerlySAIC-Frederick,MD),accordingto
cGMPregulations.Thedrugproductisasterile,aqueous,bufferedsolutioncomposedofcAd3-
EBOSdrugsubstancefilledintosingledosevialsat1x1011PU/mL.Vialsareasepticallyfilled
undercGMPtoanominalfillvolumeof1.2mL±0.1mLtoallowwithdrawalof1.0mLforIM
administration.Vialsare intendedforsingleuseonlyandthusdo notcontain a preservative.
AdditionaldetailsonVRC-EBOADC086-00-VP(cAd3-EBOS)compositionandmanufacturing
canbefoundintheInvestigatorBrochure.
The diluent, VRC-DILADC065-00-VP, was manufacturedat the VPP.It is comprised of the
formulationbufferandwillbeusedtodilutethecAd3-EBOSvaccinetopreparethe1x1010
PU/mLdosagetobeadministeredinthisstudy.TheformulationbufferispH7.4andconsistsof
10mMTris,10mMHistidine,5%Sucrose(w/v),75mMSodiumChloride,1mMMagnesium
Chloride, 0.02%Polysorbate 80(PS-80)(w/v), 0.1 mMEDTA,and0.5%(v/v)Ethanol. The
diluent is supplied in glass vials at a nominal fill volume of 1.2 mL ± 0.1 mL to allow
withdrawalof1.0mL.Vaccinedoselevelsareachievedbyadministeringtheappropriatevolume
directly from the vial or dilution to the appropriate dosage. Additional diluent VRC-
DILADC065-00-VP composition and manufacturing information can be found in the
InvestigatorBrochure.
6.2.2
StudyProductLabels
The labels for VRC-EBOADC086-00-VP (cAd3-EBO S) and VRC-DILADC065-00-VP,
diluent, will have specific product information (e.g., part number, lot number, fill volume,
storage temperature) included on the product vial labels. The vaccine label will contain an
InvestigationalUseStatement(“Caution:LimitedbyFederalLawtoInvestigationalUse”),and
manufacturerinformation.

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6.2.3
StudyProductStorage
VRC-EBOADC086-00-VP(cAd3-EBOS)willbestoredat≤-60°C,andVRC-DILADC065-00-
VP (diluent) will be stored at -45°C to -10°C, each in a qualified, continuously monitored,
temperature-controlledfreezer.
Ifdeviationsinstoragetemperatureoccurfromthenormalallowanceforthepharmacyfreezer,
thesitepharmacistmustreportthestoragetemperatureexcursionpromptlytothePIandtheIND
sponsor.Theexcursionmustbeevaluatedandinvestigatedandactionmustbetakentorestore
andmaintainthedesiredtemperaturelimits.Followingtheoutcomeoftheinvestigation,theIND
sponsorwillnotifythepharmacistifcontinuedclinicaluseoftheproductisacceptable.
6.2.4
PreparationofStudyProductforInjection
To prepare the vaccine for injection, the vial containing cAd3-EBO S and/or diluent will be
thawedatambienttemperature(15-25ºC).
Preparation will be donein a clean preparation biosafety hood with limited access. Only the
required vials will be present in the preparation unit during dilution, and medication labels
shouldbestrictlysegregatedtoavoidmix-ups.AllinjectionswillbeadministeredIMintothe
deltoidmusclebyneedleandsyringeandmustbeadministeredwithin4hoursafterremoving
thevaccinevialfromthefreezer.
ProductdilutionswillbepreparedinaClassIIbiosafetycabinet.
PreparationofVRC-EBOADC086-00-VP(cAd3-EBOS)at1x1010PUDose
Preparationofthe1x1010PUdosageofcAd3-EBOSrequiresoneserialdilution.Removeone
vial of cAd3-EBO S vaccine and two vials of diluent from the freezer and allow them to
equilibrate to roomtemperature. Using sterile syringes, draw up1.0 mL of diluent from one
diluentvialand0.35mLfromtheotherdiluentvialandinjectthesevolumesintoasterilevial.
Then,usingasterilesyringedrawup0.15mLofthe1x1011PU/mLvaccineandinjectthisinto
thevialwiththediluenttoachieveatotalvolumeof1.5mL.Vortexthevialathalfspeedfor3-5
seconds.Thisvialnowcontains1.5x1010PUcAd3-EBOSin1.5mLandhasaconcentrationof
1x 1010PU/mL. One 1 mL injection ofthis preparation will beadministered for each dose.
Discardremnantvaccineinvialinabiohazardcontainerforincineration.
PreparationofVRC-EBOADC086-00-VP(cAd3-EBOS)at1x1011PUDose
No dilution is needed for preparation of the 1 x 1011 PU dosage of cAd3-EBO S vaccine.
Removeonevialofvaccinefromthefreezerandallowittoequilibratetoroomtemperatureina
biosafetyhood.Usingasterilesyringe,withdraw1.0mLfromthevial.One1mLinjectionof
thepreparationwillbeadministered.Discardremnantvaccineinavialinabiohazardcontainer
forincineration.
6.3
Pharmacy:ProductSupply,Distribution,andAccountability
6.3.1
StudyProductAcquisition/Distribution
Thestudyproduct(s)forthisprotocolaresuppliedbytheVaccineResearchCenter,NIHand
shouldbeobtainedbyfollowingtheinstructionsintheManualofProcedures.

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6.3.2
StudyProductAccountability
The study pharmacist will be responsible for maintaining an accurate record of the codes,
inventory, and an accountability record of vaccine supplies for this study. Electronic
documentationaswellaspapercopiesmaybeused.
TheVRCwillreceivecopiesofpharmacyrecordsattheendofthestudy.
6.3.3
DisposalofClinicalSupplies
The empty vials and the unused portion of the vial should be discarded in a biohazard
containmentbag andincinerated.Anyunopenedvials(pastthe re-testdateorotherwise)that
remainwillbedestroyedatthediscretionofthesponsorinaccordancewithpoliciesthatapplyto
investigational agents in Uganda. Partially used vials or expired prepared doses will not be
administeredtootherparticipantsorusedforinvitroexperimentalstudies.Theywillbedisposed
of in accordance with institutional pharmacy policy. Retest dates shall be updated as per
analyticalanalysesof theIP.No IPshall beadministeredtoa participant beyondthe current
retestdate.

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7.0
PHARMACOVIGILENCE,SAFETY,ANDADVERSEEVENTREPORTING
7.1
Definitions
Anadverseevent(AE)isanyuntowardmedicaloccurrenceinaclinicalinvestigationparticipant
administeredapharmaceuticalproductanddoesnotnecessarilyhaveacausalrelationshipwith
this product. An AE can therefore be any unfavorable and unintended sign (including an
abnormal laboratory finding), symptom, or disease temporally associated with the use of a
medicinal (investigational) product, whether or not related to the medicinal (investigational)
product. (International Conference on Harmonization (ICH) E6) (Synonym: Adverse
Experience).
Aseriousadverseevent(SAE):Anadverseeventorsuspectedadversereactionisconsidered
"serious"if,intheviewofeithertheinvestigatororsponsor,itresultsinanyofthefollowing
outcomes: Death,a life-threatening adverseevent, inpatienthospitalization orprolongationof
existing hospitalization, a persistent or significant incapacity or substantial disruption of the
abilitytoconductnormallifefunctions,oracongenitalanomaly/birthdefect.Importantmedical
events that may not result in death, be life-threatening, or require hospitalization may be
considered serious when, based upon appropriate medical judgment, they may jeopardize the
participant and may require medical or surgical intervention to prevent one of the outcomes
listed in this definition. Examples of such medical events include allergic bronchospasm
requiringintensivetreatmentinanemergencyroomorathome,blooddyscrasiasorconvulsions
thatdonotresult ininpatienthospitalization,orthedevelopmentofdrugdependencyordrug
abuse(21CFR312.32).
“Life-threatening”referstoanadverseeventthatatoccurrencerepresentsanimmediateriskof
deathtotheparticipant.Aneventthatmaycausedeathifitoccursinamoresevereformisnot
considered life-threatening. Similarly, a hospital admission for an elective procedure is not
consideredanSAE.
All AEs will have their possible relationship to study vaccine assessed and will be graded
accordingtothetableforgradingseverityofadverseevents(seeAppendix6).Arthralgia(joint
pain)andarthritisAEswillbegradedinaccordancewiththecriteriainAppendix7.
7.2
AdverseEventGradingandRecording
RecordingofallAEswilloccurduringtheperiodfromstudyagentadministrationthrough28
daysafterstudyagentadministration.SolicitedAEswillberecordedinthestudydatabasefor7
daysafterinjectionwithoutthecollectionofattributeassessments.AllunsolicitedAEsandSAEs
thatoccurduringtheperiodfromstudyagentadministrationthrough28daysafterstudyagent
administrationwillberecordedinthestudydatabase.Afterstudyday28,onlySAEsandnew
chronicmedicalconditionsthatrequireongoingmedicalmanagementwillberecordedasAEsin
thestudydatabase.BecausethisisanEbolavaccinestudy,intheunlikelycircumstanceofEbola
virusdisease(EVD)diagnosisinastudyparticipantatanytimethroughoutthestudy,thiswillbe
recorded on an “EVD CRF”, rather than an AE form, without requiring an investigator
attribution(“relatednesstostudyagent”)orseveritygrade.
TheFDAGuidanceforIndustry(September2007):“ToxicityGradingScaleforHealthyAdult
andAdolescentVolunteersEnrolledinPreventiveVaccineClinicalTrials”wasadaptedforthe

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severitygradingofadverseeventsinthisprotocol.TheFDAGuidanceofIndustryontoxicity
grading scale is modified for criteria on absolute neutrophil counts and other parameters as
describedinAppendix6,whichalsoincludesthedefinitionsforseveritygradingparametersthat
donothavespecificguidelinesinthetable.Duetotheabsenceofspecificgradingcriteriafor
arthralgias on the FDA toxicity grading scale, the “DAIDS AE Grading Table Corrected”
(Version2.1-July2017)(Appendix7)willbeusedtogradearthralgiaAEs.
TheclinicalinvestigatorswillmonitorandanalyzestudydataincludingallAEandlabdataas
they become available and will make determinations regarding the severity of the adverse
experiencesandtheirrelationtostudyproduct.AECRFswillbecompletedbytheresearchstaff
on a daily basis as the data become available from the clinic or laboratory. AEs are also
subjectedtoanalysistoidentifythosethatmayinvokestudypauserules.ToensurethatallAEs
arecapturedinatimelymanner,AECRFswillbeenteredintothedatabasewithin24hours.All
otherCRFswillbeenteredintothedatabasewithin3businessdays.AllCRFswillbesubjected
toanalysistoidentifyAEsthatmayinvokestudypauserules.
Although post injection reactogenicity (PIR)/Solicited AEs are documented separately from
unsolicitedAEs,theywillbereportediftheymeetSAEorstudypauseruledefinitionsasnoted
below.ThereforethePIordesigneemustreviewbothPIRandAECRFstoensurepromptand
completeidentificationofalleventsthatrequireexpeditedreportingasSAEs,studypauserules
orotherseriousandunexpectedevents.
AEswillbefollowedbytheclinicalresearchteamuntilresolved,andstabilityorchronicityhas
beenestablishedanddocumented.
7.2.1
GradingandRecordingTachypnea
TheUgandaMinistryofHealth(MoH)hasputforthguidelinesforpractitionersthatindicatea
respiratory rate of 20 or more breaths per minute as abnormal, however respiratory rates in
Kampala(atanaltitudeof3900feet),whilenotwelldefined,havebeencommonlyobservedata
rateof20breathsperminute(orabove)withoutanyunderlyingoracuteillness.Giventhehigher
respiratory rate noted in guidelines and observations, any instances of a respiratory rate that
meetsthegrade1criteriainAppendix6willnotberecordedasanAEunlessitisanincrease
fromtheparticipant’sbaselinerespiratoryrateandallinstancesofgradablerespiratoryratewill
beconsideredunrelatedtotheIPintheabsenceofanyevidenceofpathologythatmayindicate
otherwise.
7.3
ProtocolSafetyReviewTeam
ThePSRTwillreviewallAEs(includingreportableAEs)onaregularandexpeditedbasisas
needed.Inaddition,thePSRTwillreviewaggregatesafetydatareportsonaweeklybasisuntil4
weeksafterallparticipantshavecompletedthevaccination,thenthesafetyreviewswilloccur
monthly.ThePSRTwillreviewSAEsthatpotentiallymeetstudypausecriteriaonanexpedited
basisandwilldecideifthestudyshouldbepausedforparticipantsafetypurposes.Thisteam
includes the following: PI or designee, Associate Investigators, Protocol Consultants, DoD
ResearchMonitor,sponsorINDMedicalOfficerordesignee,andotherVRCRepresentatives.
Additionalparticipantscouldincludestudypersonnelandseniorclinicalresearchnursingstaff.
A quorum is established with the PI or designee, one AI or designee, one MHRP protocol
consultantortheirdesignee,andINDMedicalOfficerortheirdesignee.IftheDoDResearch

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Monitor is not available for the PSRT call, they must provide input by email and then be
immediatelyemailedtheoutcomeofthePSRTdiscussion.
Inadditiontotheregularandexpeditedmeetings,thePSRTwillconductthefollowingthree
interimsafetydatareviewstoassesswhetherornotthesafetydatameetcriteriaformovingonto
thenextstageofthestudy.
ReviewforContinuationof1x1010PUDoseofVRC-EBOAD086-00-VP:Nomorethan1
participantperdaywillbeenrolledintothegroupforthefirst3participants.Whenthefirst3
participantswhohavereceivedthe1x1010PUdosehavecompletedpostvaccinationfollowup
throughatleastthe“StudyDay7”visit,aninterimsafetydatareviewwillbeconductedbythe
PSRT. Enrollment of the remaining 17 participants in the group may proceed if the PSRT
assessesthedataassafetocontinue.
ReviewforDoseEscalationto1x1011PUDoseofVRC-EBOAD086-00-VP:Whenthelast
participantwhohasreceivedthe1x1010PUdosehas completedpostvaccination followup
throughatleastthe“StudyDay7”visit,aninterimsafetydatareviewwillbeconductedbythe
PSRT.Ifthesafetydatasupportproceedingtothe1x1011dose,thenenrollmentofGroup2will
begin.
ReviewforContinuationof1x1011PUDoseofVRC-EBOAD08600-VP:Nomorethan1
participantperdaywillbeenrolledintothegroupforthefirst3participants.Whenthefirst3
participantswhohavereceivedthe1x1011PUdosehavecompletedpostvaccinationfollowup
throughatleastthe“StudyDay7”visit,aninterimsafetydatareviewwillbeconductedbythe
PSRT. Enrollment of the remaining 17 participants in the group may proceed if the PSRT
assessesthedataassafetocontinue.
After each of these interim safety reviews, the IRB, NDA and VRC will be provided with
documentationofthesafetyreviewandnotificationoftheplan.
7.4
SafetyMonitoringCommittee(SMC)Reviews
TheSMCforthisstudywillbecomprisedofanindependentgroupofexpertswhoreviewsafety
dataduringtheclinicaltrial.TheSMCwillmeetasneededtodeliberateuponthedispositionof
studypausesand/ortoprovideotherrecommendationsregardingthesafeconductofthestudyas
requestedbythePIandstudyteam.OtherwisetheSMCwillreviewstudydata,ataminimum
annuallyfromthetimethestudyopened.TheSMCExecutiveSecretarywillprovidethePIand
studyteamwithSMCrecommendations,andthePIandMHRPConsultantswillinformIRBs
and regulatory authorities as appropriate. The VRC will notify the FDA of the SMC
recommendationasneeded.
7.5
CriteriaforStudyPauseorTermination
The PI will closely monitor and analyze study data as they become available and will make
determinations regarding the presence and severity of adverse events. The administration of
study injections and new enrollments will be paused and the IND Sponsor will be promptly
notifiedaccordingtothefollowingcriteria:

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· One(ormore)participantexperiencesaSAEthatisassessedaspossibly,probablyor
definitelyrelatedtostudyagent,or

· Two(ormore)participantsexperiencethesameGrade3or4adverseeventassessedas
possibly,probablyordefinitelyrelatedtostudyagent.
PlanforReviewofPausesandResumingRules:
The study injectionsand enrollments wouldresumeonlyif review oftheadverse events that
caused the pause resulted in a recommendation to permit further study injections and study
enrollments.Thereviewstomakethisdecisionwilloccurasfollows:
PausesforSAEs:TheINDSponsorandPSRTwillconsultwiththeSMCtoconductthereview
andmakethedecisiontoresume,amendorclosethestudyforanySAEsthatmeetthecriteria
forpausingthestudy.TheFDAwillbenotifiedofanySAEpausereview.
PausesforGrade3or4AEs:TheINDSponsorandPSRTwillconductthereviewandmake
thedecisiontoconsulttheSMC,resume,amendorclosethestudyfortheGrade3or4events
thatmeetthecriteriaforpausingthestudy.Aspartofthepausereview,thereviewerswillalso
adviseonwhetherthestudyneedstobepausedagainforanysubsequentGrade3or4eventof
thesametype.TheFDAwillbenotifiedofallGrade3or4pausereviews.
Whenindicated,safetydatareportsandchangesinstudystatus(studypauses)willbesubmitted
totheIRBinaccordancewithinstitutionalpolicy.
7.6
ReportingSeriousandUnexpectedAdverseEvents
7.6.1
StudyReportingPeriodforSAEs
The protocol-defined expedited event reporting period is 48 weeks after study agent
administration(studycompletion)ordiscontinuationoftheparticipantfromstudyparticipation
foranyreason.Aftertheendoftheprotocol-definedSAEReportingPeriodstatedabove,sites
must report suspected unexpected serious adverse reactions (SUSARs) if the study site staff
becomesawareoftheeventfromaparticipantonapassivebasis(i.e.,frompubliclyavailable
information).
7.6.2
AdverseEventReportingtotheINDSponsor
AllSAEsmustbereportedandsubmittedbytheclinicalsiteonanexpeditedbasistotheIND
sponsor,VRC/NIAID/NIH,accordingtosponsorguidelinesasfollows:
· resultsindeath
· islifethreatening
· resultsinpersistentorsignificantdisability/incapacity
· requiresunplannedinpatienthospitalizationorprolongationofexistinghospitalization
· isacongenitalanomaly/birthdefectintheoffspringofastudyparticipant
·
isanimportantmedicaleventthatmayjeopardizetheparticipantormayrequireintervention
topreventoneoftheotheroutcomeslistedabove

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Inaddition,anyevent,regardlessofseverity,whichinthejudgmentofaninvestigatorrepresents
aseriousadverseevent,maybereportedonanexpeditedbasis.
AninvestigatorwillcommunicatetheinitialSAEreportwithin24hoursofsiteawarenessof
occurrencetotheINDsponsorthroughoutthestudyreportingtimeperiod.NotificationofSAEs
willbesentviaemailtothePSRT,whichincludestheINDMedicalOfficer.
AwrittenreportbyinvestigatorshouldbesubmittedtotheINDSponsorwithin3workingdays.
In order for the IND Sponsor to comply with regulations mandating sponsor notification of
specified SAEs to the FDA within 7 calendar days, the investigator must submit additional
informationassoonasitisavailable.
7.6.3
INDSponsorReportingtotheFDA
TheINDSponsorisresponsibleformakingthedeterminationofwhichSAEsareSUSARsthat
meetcriteriaforexpeditedreportingasdefinedin21CFR312.32.
· Suspectedadversereactionmeansanyadverseeventforwhichthereisareasonable
possibilitythatthedrugcausedtheadverseevent.
· UnexpectedAdverseEventmeansanAEthatisnotlistedintheInvestigator’sBrochure
orisnotlistedatthespecificityorseveritythathasbeenobserved.
The INDSponsorwillsubmitwrittenINDSafetyReportsto theFDAinaccordancewith21
CFR312.32assoonaspossibleand,innoevent,laterthan15calendardaysafterdetermining
thattheinformationqualifiesforreporting.
TheINDSponsorisresponsibleforprovidingcopiesofINDSafetyReportsforsubmissionto
theMUSPHIRB,UNCSTandNDAasapplicable.
7.6.4
ReportingSeriousandUnexpectedAdverseEventstotheLocalRegulatory
Bodies&InstitutionalReviewBoards
AllSAEsregardlessofrelationshiptotheinterventionandallunexpectedevents(whosenature,
severityorfrequencyhadnotbeenidentifiedintheInvestigator’sBrochureortheprotocol)of
greaterthanmoderateseverityregardlessofrelationshiptotheintervention,toincludeSUSAR,
mustbereportedtotheMUSPHIRBandtheNDAassoonaspossibleandinanycasenolater
than7calendardaysofbecomingawareoftheevent.Thereafter,adetailedreportoftheSAE
shouldbesubmittedwithin7days.
AllotherreportableadverseeventsshouldbereportedtotheIRBassoonaspossibleandinany
casenolaterthan14calendardays.Theseinclude:
a. Alleventsassociatedwithprotocolviolationsregardlessofseverityandrelationshipto
theintervention;
b. Whenthecriteriaforstoppingorpausingastudyasstipulatedintheprotocolismet;
c. Anyeventmandatedbyregulatoryauthorities;
d. Anyeventstipulatedintheprotocolasreportabletotheregulatorybodies.

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Followupreportswillbesubmittedasadditionalinformationbecomesavailable.Asummaryof
thenon-seriousadverseeventsandSAEs(bothrelatedandunrelated)thatoccurredduringthe
reportingperiodwillbeincludedinthecontinuingreviewreport(CRR)totheMUSPHIRB.
7.6.5
ReportingSeriousandUnexpectedAdverseEventstoWRAIRandHRPO
AllSAEsthatareconsideredrelatedorpossiblyrelated,andalldeaths,willbepromptly(within
48hours)reportedtotheWRAIRHSPB.Writtenreportswillbesubmittedwithin10working
daystotheWRAIRHSPB.TheWRAIRHSPBwillreportSAEstoUSAMRDCORPHRPOas
perSOPUWZ-C-636.Followupreportswillbesubmittedasadditionalinformationbecomes
available.
TheWRAIRHSPBwillbeimmediatelynotifiedifanystudypausecriteriaaremet.WRAIR
HSPBwillforwardtoUSAMRDCORPHRPOasperSOPUWZ-C-636.
7.7
UnanticipatedProblemsReporting
Allnon-seriousunanticipatedproblems(eventsnotinvolvingrisktoparticipantsorothers)will
bereportedinthecontinuingreviewreporttotheMUSPHIRB.
Allseriousunanticipatedproblemsinvolvingrisktosubjectsorothers(UPIRTSOs)(including
butnotlimitedtodisclosureofpersonalhealthinformation,breachofconfidentiality,destruction
orlossofstudyrecords,unaccountedforstudydrug,etc.)shouldbepromptly(within48hours)
reportedtotheWRAIRHSPBandtheINDsponsorviaemail.ThePIwillthenforwardawritten
reportwithin10workingdaystotheWRAIRHSPB.
All unanticipated events of greater than moderate severity, regardless of relationship to the
intervention,willbereportedtotheMUSPHIRBassoonaspossibleandinanycasenolater
than7calendardaysofbecomingawareoftheevent.Adetailedreportoftheunanticipatedevent
shouldbesubmittedwithin7calendardaysfromthedateitisreportedtotheMUSPHIRB.
Followupreportsshouldbesubmittedassoonasadditionalinformationbecomesavailable.A
summaryoftheseriousunanticipatedproblemswillalsobeincludedinthecontinuingreview
reportsubmittedtotheMUSPHIRBandNDA.
Unanticipatedproblemsrelatedtotheinvestigationalproduct,suchasproblemswiththeactual
product itself (e.g. visible discoloration or particulate matter not consistent with product
description), will be promptly reported to the study sponsor (for reporting to the US FDA),
MUSPHIRBandNDAbythePI.
The DoD medical monitor should also review all unanticipated events involving risk to
participants orothers andprovidean independentassessment for submissionto VRC/NIAID,
WRAIRHSPB,MUSPHIRB,andNDA(asapplicable).TheWRAIRHSPBwillreportserious
unanticipatedproblems,followupreportsandDoDmedicalmonitorreportstotheUSAMRDC
ORPHRPOasperUWZ-C-636.

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8.0
STATISTICALCONSIDERATIONS
8.1
Overview
TheprimaryobjectiveofthisstudyistoassessthesafetyandtolerabilityofcAd3-EBOSattwo
doselevels.ThesecondaryobjectiveistoevaluatetheantibodyandEbolaSudanGP-specificT-
cellresponsestotheGPinsertandcAd3vectorat4weeksaftervaccination.Anexploratory
evaluation of immunogenicity, including assays with samples collected at different study
timepoints, profiling vaccine-induced mRNA expression, and isolating MAbs to determine
epitopespecificity,willalsobeperformed.Atotalof40participantswillbeenrolledwith20to
receivea1x1010PU/mLdoseand20toreceivea1x1011PU/mLdoseofthecAD3-EBOSand
followedupthrough48weekspost-vaccination.
8.2
SampleSizeandAccrual
8.2.1
PowerandSampleSizeCalculationsforSafety
The goal ofthesafety evaluationforthis study isto identifysafety concerns associatedwith
vaccination.Occurrenceofsolicitedlocalandsystemicreactogenicitysymptoms,occurrenceof
adverse and serious adverse events will be assessed as the proportion of participants
experiencingsuchsafetyevent.Table4belowshows95%confidenceintervalsfor0,1,2,5,and
10participantswithobservedeventsineachgrouporamongallstudyparticipants.
Table4.
Exact95%ConfidenceIntervalsfortheProportionofParticipants
ExperiencingaSafetyEvent

Ifnoparticipantsexperienceanevent,theupperlimitofatwo-sidedexact95%CIwouldbe
16.8% for an individual group and 8.8% for the entire study group. While this study is not
necessarilypoweredtodetectdifferencesbetweengroups,wewouldhave82%powertodetecta
differenceof40%(p1=0.1andp2=0.50)usingBarnard’sexactunconditionaltestata5%two-
sidedlevelofsignificance.
Changes in laboratory measures from baseline will also be described. For continuous safety
measures,Table5belowshowsminimumdetectablechangesfrombaselinetoaspecifiedtime
pointusingapairedt-testwithatwo-sided5%leveltest.
Group
Sample
Size
NumberofParticipantswithanEvent(s)Observed
0
1
2
5
10
Each
Individual
StudyGroup
20
0%
(0%-16.8%)
5%
(0.1%-24.9%)
10%
(1.2%-31.7%)
25%
(8.6%-49.1%)
50%
(27.2%-72.8%)
All
participants
40
0%
(0%-8.8%)
2.5%
(0.06%-13.2%)
5%
(0.6%-16.9%)
12.5%
(4.2%-26.8%)
25%
(12.7%-41.2%)

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Table5
MinimumDetectableDifferences,inStandardDeviations,forChangeFrom
BaselinetoaSingleTime(2-sidedα=0.05)
Group
SampleSizes
Power
80%
85%
90%
1(1x1010 PU/mL)
15
0.78
0.83
0.9
2(1x1011 PU/mL)
20
0.66
0.71
0.76
AllActive
35
0.49
0.52
0.56

Ifcomparingthetwostudy groups,wewouldhave80%powertodetectadifferenceof0.91
standard deviations usingatwo-sample t-testwith atwo-sided5% alpha andassumingequal
variances.
8.2.2
PowerandSampleSizeCalculationsforImmunogenicity
The precisionand power calculations forsafety shown in Table4 andTable 5 also apply to
immunogenicityresults.Resultsofimmunogenicityassessmentscanbeshownasproportionof
responders (Table 4 applied) or continuous measures (Table 5 applied). For example, if we
observe 10 positive responses from an ELISA assay in an individual group, the 95% exact
confidence interval of the true response rate will range from 0.272 to 0.728. Note that
immunogenicityisasecondaryobjectiveforthisprotocol.
8.3
StatisticalAnalysis
Allanalyseswillbedescribedoverallandbyvaccinationgroup(Group1andGroup2).The
safety and immunogenicity analysis will include all vaccinated participants. All statistical
analyses will be performed using Statistical Analysis System (SAS), R, or S-Plus statistical
software.Noformalmultiplecomparisonadjustmentswillbeemployedforsafetyendpointsor
secondaryendpoints.
8.3.1 BaselineDemographics
Baselinedemographicsandlaboratorymeasurementswillbesummarizedforindividualgroups
and overall. Categorical variables will be reported in numbers and percents with exact 95%
Clopper-Pearson confidence intervals. Continuous variables will be reported in means and
standarddeviationsormediansandIQRasappropriate.
8.3.2 SafetyAnalysis
Safety and tolerability will be assessed by both clinical and laboratory monitoring. If
comparisons are performed between groups, then Barnard’s exact unconditional test will be
performedforbinaryvariablesandt-tests(orWilcoxonRankSumasappropriate)forcontinuous
measures.
Reactogenicity
The number and percentage of participants experiencing each type of reactogenicity sign or
symptomwillbetabulatedbystudygroupandseverity.Exact95%Clopper-Pearsonconfidence
intervals will be calculated for each set of events. For a given sign or symptom, each
participant’s reactogenicity will be counted once under the maximum severity for all
assessments.

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AdverseExperiences
Adverse experiences are codedinto Medical Dictionary forRegulatory Activities (MedDRA)
system organ classes and preferred terms. The number and percentages of participants
experiencing each specific adverse event will be tabulated by dose level, severity and
relationshiptotreatment.Forthetabulationoftheadverseexperiencesbysystemorganclass,a
participantwascountedonlyonceinagivenbodysystem.Forexample,aparticipantreporting
gastritisanddiarrheawillbereportedasoneparticipant,butthesymptomswillbelistedastwo
separateAEswithintheclass.Acompletelistingofadverseexperiencesforeachparticipantwill
providedetailsincludingpreferredterm,systemorganclass,severity,relationshiptotreatment,
onsettime,durationandoutcome.
LocalLaboratoryValues
Boxplotsoflocallaboratoryvalueswillbegeneratedforbaselinevaluesandforvaluesmeasured
duringthecourseofthestudy.Eachboxplotwillshowthe1stquartile,themedian,andthe3rd
quartile.Outliers,orvaluesoutsidetheboxplot,willalsobeplotted.Ifappropriate,horizontal
linesrepresentingboundariesforabnormalvalueswillbeplotted.Tableswillbeprovidedfor
changesfrombaseline.
8.3.3 ImmunogenicityAnalysis
Immunogenicityanalysiswillconsistofallvaccinatedparticipants.Ifassaydataarequalitative
(i.e., positive or negative) then analyses will be performed by tabulating the frequency of
positiveresponseforeachassayateachtimepointthatanassessmentisperformed.Binomial
response rates will be presented with their corresponding exact 95% confidence interval
estimates.Barnard'sunconditionalexacttestswillbeusedtocomparethetwo groupstoeach
other. For quantitativeresults, mean andstandarddeviation willbecalculated.One-sample t-
tests will be used to assess the changes from baseline. Two-sample t-tests will be used to
comparethetwostudygroups.Missingresponseswillbeassumedtobemissingatrandom,i.e.,
conditionalontheobserveddatathemissingnessisindependentoftheunobservedresponses.
Graphicaldescriptionsofthelongitudinalimmuneresponseswillalsobegiven.
Some immunologic assays have underlying continuous or count-type readout that is often
dichotomizedintoresponder/non-responder categories.Fortheseassays,graphicalandtabular
summariesoftheunderlyingdistributionswillbemade.Thesesummariesmaybeperformedon
transformed data (e.g., log transformation) to better satisfy assumptions of symmetry and
homoscedasticity.
8.3.4 InterimAnalyses
SafetyReviews:ThePSRTwillreviewsafetydataroutinelythroughoutthestudy.Thestudy
willutilizebothelectronicdatabasefeaturesandreviewsbydesignatedsafetyreviewpersonnel
toidentifyinatimelymannerifanyofthesafetypauserulesofthestudyaremet.TheSMCwill
reviewstudydataonanannualbasisfromthetimethestudyopened.
Immunogenicity Review: Periodic analyses of immunogenicity for each group may be
performedduringthestudyforthepurposeofinformingfuturevaccine-relateddecisions ina
timely manner once there are at least 3 participants in the group with the 4 weeks post
vaccinationfollow-upcompleted.Theresultswillnotinfluencetheconductofthetrialinterms
ofearlyterminationorlatersafetyorimmunogenicityendpointassessments.

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9.0
SAMPLEANDDATAMANAGEMENT
9.1
PlanforUseandStorageofBiologicalSamples
9.1.1
UseofSamples,SpecimensandData
Samples, specimens and data collected under this protocol will be used to conduct protocol-
relatedsafetyandimmuneresponseevaluations,exploratorylaboratoryevaluationsrelatedtothe
type of infection the study agentwas designed to prevent, exploratory laboratory evaluations
related to vaccineorinfectious disease research in general and for research assay validation.
Genetic testing will be performed in accordance with the information included in the study
informed consent for genetic testing (Appendix 2c). Results from genetic testing will not be
providedtoparticipantsasthetestresultsarenotvalidatedforclinicaluse.Allsafetylabswillbe
performedatthestudysite.
Immunogenicity of the vaccine will be evaluated as humoral and cellular immune responses
assessed byELISAandintracellular cytokinestaining(ICS) assay. TheELISA assay willbe
performed at the VRC or VIP and the exploratory evaluation of Ebola-specific neutralizing
antibodies will be conducted at the VRC, using previouslypublished methods [21]. The pre-
existingandpost-vaccinationpresenceofcAd3neutralizingantibodyalsowillbeevaluated[32].
The ICSassayquantitatesthefrequencyofCD4+andCD8+cellsthatproduceinterleukin-2,
interferon-gamma and/or tumor necrosis factor in response to pools of overlapping peptides
representingEbolaGPantigensandisbaseduponpreviouslypublishedmethods[35].
Other evaluations of vaccine-induced immune responses may be conducted as exploratory
evaluations.SpecificpeptidesmaybeusedtodetectT-cellresponsivenessbyanenzyme-linked
immunospot (ELISpot) assay, modified from a previously published method [33]. Genetic
factorsassociatedwithimmuneresponsesmayalsobeevaluated;isolationofMAbstodetermine
epitope specificity and functional capacity may be performed; and time courses of immune
responsesmaybeanalyzedincludingdurabilityofcAd3neutralizingantibodytiters,mediators
of inflammation following vaccination, and, for the first week, vaccine-induced mRNA
expressionprofiles.
Storedsamplesfromvaccinestudyparticipantsmayalsobeusedinthefutureforevaluationof
immune response to the vaccine as measured by other assays. The experimental laboratory
proceduresfortheexploratoryobjectivesmaybeconductedusingfreshorstoredsamplesatthe
NIHoratthelaboratoriesofitsaffiliatesand/orcollaborators(seeAppendix13).
9.1.2
StorageandTrackingofBloodSamplesandOtherSpecimens
AllofthestoredstudyresearchsampleswillbelabeledwithaparticipantIDnumberthatonly
thesitecanlinktotheparticipant.SampleswillbestoredatVIPorattheVRCImmunology
Laboratory in Building 40; all are secure facilities with limited access. Data will be kept in
password-protected computers. Only investigators or their designees will have access to the
samplesanddata.SampleswillbetrackedintheLaboratoryInformationManagementSystem
(LIMS)databaseorusinganothersoftwaredesignedforthispurpose(e.g.,Freezerworks).

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9.1.3
DispositionofSamples,SpecimensandDataatCompletionoftheProtocol
Atthetimeofprotocoltermination,sampleswillremainatVIP,VRCor,afterIRBapproval,
transferredtoanotherrepository.Atthistime,alistofallparticipantswhorefusedfutureuseof
theirsampleswillbegeneratedfromthestudydatabaseandthecorrespondingsampleswillbe
destroyed.DatawillbearchivedbytheVRCincompliancewithallrequirementsforretentionof
researchrecords, orafterthe IRBandthe IND sponsorapproval, may beeitherdestroyedor
transferredtoanotherrepository.
9.1.4
LossorDestructionofSamples,SpecimensorData
Anylossorunanticipateddestructionofsamples(forexample,duetofreezermalfunction)or
data(forexample,misplacingaprintoutofdatawithidentifiers)thatcompromisesparticipant
confidentialityorthescientificintegrityofthestudywillbereportedtotheIRBinaccordance
withSection7.7.ThePIwillalsonotifytheIRBifthedecisionismadetodestroytheremaining
samples.
9.2
StudyDocumentationandStorage
Theinvestigatorwillmaintainalistofappropriatelyqualifiedpersonstowhomtrialdutieshave
beendelegated.
Sourcedocumentsareoriginaldocuments,data,andrecordsfromwhichtheparticipant’sdata
areobtained.Theseincludebutare notlimitedtohospitalrecords, clinicaland office charts,
laboratoryandpharmacyrecords,diaries,radiographs,andcorrespondence.
The investigator and staff are responsible for ensuring maintenance of a comprehensive and
centralizedfilingsystemofallstudy-related(essential)documentation,suitableforinspectionat
anytimebyrepresentativesofUSAMRDCORPHRPO,WRAIR,FDA,theU.S.DoD,MUSPH
IRB, UNCST, NDA, the sponsor, and other regulatory agencies. Essential documents for all
studyparticipantsaretobemaintainedbytheinvestigatorsinasecurestoragefacility.Elements
include:
· Participant files containing completed informed consent forms, and copies of source
documentation
· Study files containing the protocol will include all amendments and copies of
correspondencebetweenthestudysite,protocolteamandtheIRB
· AllEssentialDocumentsoutlinedintheICHGoodClinicalPracticeGuideline.
Inaddition,alloriginalsourcedocumentationmustbemaintainedandbereadilyavailablefor
monitoringorauditingpurposes.
AllessentialdocumentationwillbecollectedbyEMMESintheRegulatoryTrackingSystem
andshouldberetainedforthesameperiodoftimerequiredformedicalrecordretention.The
FDArequiresstudyrecordstoberetainedfor2yearsaftermarketingapprovalorrefusal(21
CFR 312.62), the NIH requires study record retention for a minimum of 7 years after study
closure,andtheUNCSTguidelinesrequirerecordstoberetainedforaminimumof5yearspost-
studyclosure.StudyrecordswillberetainedforatleastaslongasisrequiredbytheFDA,NIH
and UNCST record retention requirements. No study document or data should be destroyed

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withoutpriorwrittenagreementbetweenVRC,theMHRPConsultantsandthePI.ShouldthePI
wishtoassignthestudyrecordstoanotherpartyormovethemtoanotherlocation,VRCmustbe
notifiedinwritingofthenewresponsiblepersonand/ornewlocation.
TheVRCmayrequesttoreceiveacopyofallessentialdocuments.FDAform1572,CVsand
IRBapprovalsmustbesubmittedtotheVRCasINDSponsor.
9.3
DataCollection
Clinicalresearchdatawillbecollectedinasecureelectronicdatamanagementsystemthrougha
contractorganization,EMMES(Rockville,MD).Data enteredintothe electronicdatasystem
shallbeperformedbyauthorizedindividuals.Correctionstotheelectronicdatasystemshallbe
tracked electronically (password protected) with time, date, individualmaking the correction,
andwhatwaschanged.
The investigator is responsible for assuring that the data collected is complete, accurate, and
recordedinatimelymanner.Sourcedocumentation(thepointofinitialrecordingofinformation)
shouldsupportthe data collected inthesystem, andmust be signed anddatedbythe person
recordingand/orreviewingthedata.Extracteddatawithoutparticipantidentifierswillbesentto
theProtocolStatisticianforstatisticalanalysis.
ThisdatawillnotcontainparticipantnamesorSocialSecurityorothernationalidentification
number,butisreferencedonlybythestudyspecificidentificationcode.
Everyattemptmustbemadetoadheretotheapprovedprotocolandtoobtainandrecordalldata
requestedforeachparticipantatthespecifiedtimes.However,ethical considerationsorother
eventsmayresultinthefailuretoobtainandrecordcertaindata,ortorecorddataatthetimes
specified.Ifthisoccurs,theeventsand,thereasonsfortheeventmustbeclearlydocumentedon
theCRFfordeviationsandreportedasapplicable.
AnalysisfilesarecreatedonaperiodicbasisandmadeavailabletotheMHRPConsultants,PI,
andAIs.Othercollaboratorsmaybegivenaccesstotheseanalysisfiles,ordatagatheredfrom
them,atthedirectionofthePI.

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10.0
ETHICALCONSIDERATIONS
10.1
Risks
10.1.1
RisksofthecAd3EbolaVaccinesandDiluent
Potential side effects resulting from intramuscular injection include pain, stinging, arm
discomfort,rednessoftheskin,soreness,itchiness,swellingormildbruisingatvaccineinjection
sites. Study participants can receive medications such as acetaminophen, NSAIDs, or
antihistaminesasrequired.
Participantsmayexhibitgeneralsignsandsymptomsassociatedwithadministrationofavaccine
includingfever,chills,rash,achesandpains,nausea,headache,dizzinessandfatigue.Theseside
effectswillbemonitored,butaregenerallyshorttermanddonotrequiretreatment.Aswithall
vaccines,anallergicreactionispossibleandwillbemanagedaspersiteSOPforanaphylaxis.To
mitigatethisrisk,participantswillremainunderobservationintheclinicforatleast30minutes
post-injection.
Chimpanzeeadenoviralvectorvaccineshavebeengenerallysafeinhealthyadultsatdosagesup
to 1011 PU per injection in completed and ongoing clinical trials [17, 28, 29]. Systemic
reactogenicitytypicallyoccursonthedayofordayaftervaccinationandmayincludeheadache,
malaise,myalgia,chills,andfever.Whenpresent,feveronsetoccurswithin1dayofvaccination
andtypicallyresolveswithin24hoursofonset.Apatternoffeveroccurringlaterthan1dayafter
vaccinationorlastinglongerthan1daymayrequireevaluationforadditionaletiology.
Risksofthevaccinetopregnantandnursingwomenandtotheunbornfetusareunknown.
Theremaybeotherunknownsideeffects.
10.1.2
OtherRisks
Blood drawing with needles, like injections, may cause pain, bruising, feeling lightheaded,
fainting,and,rarely,infectionatthesitewherethebloodistaken.
Therisktopregnantwomenandfetusesiscurrentlyunknown.Assuch,womenofreproductive
potentialwillberequiredtoagreetousebirthcontrolforsexualintercoursebeginningatleast21
dayspriortoenrollmentandcontinuethrough24weeksafterthestudyinjection.Becausethisis
aresearchstudy,womenofreproductivepotentialwillbeaskedtonotifythesiteimmediately
upon learning of a pregnancy during this study and will be tested for pregnancy prior to
administrationofthestudyinjection.Theamountofblooddrawnwillbereducedatfollow-up
visitsforpregnantparticipantsasbloodwillonlybedrawnforsafetytesting.Theparticipantwill
becontactedtoaskabouttheoutcomeofapregnancythatbeginsduringthestudy.
Itispossiblethatthestandardmedicaltestsperformedaspartofthisresearchprotocolwillresult
innewdiagnoses.Dependingupon themedicalfindingsand consequences ofbeingprovided
withthenewmedicalinformationabouthealthstatus,thestudyparticipantmayviewthisaspect
of study participation as either a risk or a benefit. Any such information will be shared and
discussed with the participant and, if requested by the participant, will be provided to the
participantforreviewbytheprimaryhealthcareproviderforfurtherworkupandmanagement.

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10.2
Benefits
Althoughstudyvolunteersmay benefitfrom clinicaltestingandphysicalexaminations,study
participantswillreceivenodirectbenefitfromparticipation.
InlightoftherecentEbolaoutbreakin6countriesinWestAfricathatkilledmorethan5,160
people (of an estimated 14,000 cases) and its potential for international spread, the general
populationinUganda(andWestAfricainparticular),maybenefitfrominformationgainedfrom
thedevelopmentofavaccineagainstEbola.Further,Ugandahasitselfexperienced3outbreaks
ofEbolabetween2000and2012withacasefatalityraterangingfrom25%to71%.Whileprior
outbreaks of EVDhave been localized to various regions within Africa, there is a continued
potentialthreatofspreadtoothercountriesgiventhefrequencyofinternationaltravel.
Othersmaybenefitfromknowledgegainedinthisstudythatmayaidinthedevelopmentofan
Ebolavirusvaccine.
10.3
InformedConsent
ThestudyinformedconsentsareprovidedinAppendix2.Themainstudyconsentdescribesthe
IPtobeusedandallaspectsinvolvedinprotocolparticipation.
Beforeavolunteermayparticipateinthestudy,itistheinvestigator’sresponsibilitytoobtain
writteninformedconsentfromthepotentialparticipant,afteradequateexplanationoftheaims,
methods,anticipatedbenefits,andpotentialhazardsofthestudyandbeforeanyprotocol-specific
proceduresorstudymedicationsareadministered. Informationwillbe giveninbothoraland
writtenformwheneverpossibleasdeemedappropriatebytheIRBs.Theinvestigatorordesignee
(e.g.,studycoordinator)shallgivetheparticipantampleopportunitytoinquireaboutdetailsof
thestudy,discusswithotherpeopleandaskanyquestionsbeforedatingandsigningtheconsent
forms. Participant information and consent form language will be at a reading level fully
comprehensibletotheprospectiveparticipants.Informedconsentwillbeobtainedinaccordance
with21CRF50,DoDCommonrule,32CFR219,ICHharmonizedTripartiteGuidelineforGCP
(E6),theprinciplesoftheBelmontReport,UNCSTguidelines,andallapplicableregulations.
Eachparticipant’ssignedinformedconsentdocumentswillbekeptonfilebytheinvestigatorfor
inspectionbyRegulatoryAuthoritiesand/orRegulatoryCompliancepersons. Eachparticipant
willreceiveacopyofthesignedanddatedwritteninformedconsentdocumentalongwithacopy
ofthevolunteereventschedule.TheinformedconsentprocesswillbedocumentedintheCRFs.
Thelegalageatwhichindividualscanprovidetheirownconsenttoparticipateinresearchis18
years.ConsentformswillbeavailableinEnglishandLuganda.Thevolunteerwillsignanddate
theconsentform.Illiterateparticipantswillnotbeenrolledintothisstudyforsafetypurposes.
Participantsmustbeabletoreadandcomprehendallwritteninformationintheinformedconsent
formsandmustbeabletoaccuratelydocumentanysymptomsonthediarycardssoastoinform
theinvestigatorsaboutany adverse eventsorreactionsthatmaybeassociatedwiththestudy
vaccine.
Three(3)differentconsentformsandonewithdrawalformwillbeusedforthisstudy:
i.MainInformedConsentForm(Appendix2a)
ii.FutureUseInformedConsentForm(Appendix2b)

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iii.InformedConsentforGeneticTesting(Appendix2c)
The participant may terminate participation in the study at any time for any reason without
penalty.Additionally,intheeventthattheparticipantisunableorunwillingtoadheretothe
protocoldesign,theinvestigatormayterminatetheirparticipationforsafetypurposes.
10.4
Language
Allwritteninformationandothermaterialtobeusedbyparticipantsandinvestigativestaffmust
usevocabularyandlanguagethatareclearlyunderstood.Accordingly,theconsentandallother
writtenmaterialswillbetranslatedintoLugandainadditiontoEnglishandwillbesubmittedto
theIRBsforreviewandapproval.
10.5
Compensation
Participants will be compensated for time and inconvenience in accordance with the local
standards and legal obligations for compensation required by the study site. Any applicable
guidelinesbyIRBs/ECsforcompensationofresearchparticipantswillbesoughtandfollowed.
Participants will receive50,000 Ugandan shillings fortime, inconvenience and transportation
costsassociatedwitheachscheduledvisit,and20,000Ugandanshillingsforeachunscheduled
visit to address safety concerns. Compensation for unscheduled visits will be at the
Investigator’s/designee’sdiscretion.
10.6
PolicyRegardingResearch-RelatedInjuries
Participantswhoexperienceillnessorinjuryarisingfromparticipationinthestudywillreceive
medicalcareforsuchillnessorinjuryuntilcureorstabilizationwithcostsforsuchcareprovided
byalimitedset-asidefundandaclinicaltrialsmedicalinsurancepolicythatwillbeobtainedby
MHRP(HJF).Whileitisanticipatedthatthecombinationoftheset-asidefundandtheinsurance
policyismorethanenoughtopayfortheresearchrelatedinjurymedicalcarecostassociated
with this study, there is a limit to the amount of coverage available. The study sponsor,
MUWRP,andtheU.S.DoDwillnotprovidelong-termmedicalcareorfinancialcompensation
forstabilizedresearch-relatedinjuries.Thiswillnotwaiveaparticipant’srights.
10.7
ParticipantConfidentiality
ThePIwillmaintainparticipantresearchrecordsatthesiteforthisstudy.Allparticipantswill
receivestudynumbersthatareknownonlytotheinvestigatorsandstudystaff.Allsamplesand
documents(withtheexceptionoftheconsentforms)willbelabeledonlywithaparticipant’s
study number and not personal information. The link between a participant ID number and
participantidentifiableinformationwillbemaintainedinasecure,lockedfilecabinetinalocked
room which is accessible only to the PI/designees. Clinical and research records may be
reviewed by representatives of USAMRDC ORP HRPO, WRAIR, FDA, the U.S. DoD,
MUSPH, UNCST, NDA, the sponsor, and other regulatory agencies as part of their
responsibilitiesforinsuringtheprotectionofresearchparticipants.
Everyeffortwillbemadetokeeptherecordsasconfidentialaspossiblewithinthelimitsofthe
law. All data and medical information obtained about participants as individuals will be
considered privileged and held in confidence. Research and clinical information relating to

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participants will be shared with other investigators and the scientific community through
presentationorpublication;however,participantswillNOTbeidentifiedbynameornational
registration number. Electronic data will be stored for at least 2 years after the IND is
inactivated.
10.8
FutureUseandStorageofBloodSamples
Eachstudyparticipantwillbeaskedtoseparately,andvoluntarilyconsenttogenetictestingand
fortheirsamplestobestoredforfutureresearchstudiesthatmaybeconductedafterthisstudyis
completed.Futuretestingmayinvolvegenetictestsasindicatedinthefutureuseconsentform.
Resultsfromgenetictesting,whetherforthisstudyorfromfuturegenetictesting,willnotbe
provided to participants asthe results are not validated for clinicaluse. As statedabove, the
samplewillbelabeledonlywiththeparticipantIDthatcanbelinkedtotheirstudyinformation.
Allsamplesforwhichfutureuseconsenthasbeenobtainedandforwhichadditionalmaterialis
availableafterstudyspecifiedtestingiscompletewillbestoredforfuturetestingatVIP.

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11.0
REGULATORYREPORTINGREQUIREMENTS
11.1
ProtocolDeviationReporting
A protocol deviation is defined as an isolated occurrence involving a procedure that did not
followthestudyprotocol.
The timeline for reporting protocol deviations is determined by the categorization of the
deviation:(1)emergent/significantor(2)non-emergent/minor.Protocoldeviationsarisingofor
leadingtounanticipatedproblemsshouldbereportedintheappropriatetimeframeaccordingto
theseriousnessoftheeventasasignificantdeviationoraminordeviation.Theunanticipated
problemwillbesubmittedasdescribedinSection7.7.
Emergent/significantdeviationsaredeparturesfromprotocolthathaveasignificantimpacton
thewelfareorsafetyofaparticipantorontheintegrityofthestudydata.Examples:providing
the wrong labresult toa participantorfailure toobtaina scheduled blooddrawformultiple
participants.ChangesinprotocolproceduresmaybeinitiatedwithoutpriorIRB/ethicalreview
committee (ERC) and VRC approval, only in cases where the change(s) is /are necessary to
eliminate an immediate apparent hazard. Emergent/significant deviations should be reported
promptly(within48hours)totheWRAIRHSPBandtheINDsponsorandwithin7calendar
days to the MUSPH IRB and NDA, upon becoming aware of the event. A written report is
requiredtobesubmittedbythePItotheWRAIRHSPBandtheVRCwithin10workingdays
andtotheMUSPHIRBandNDAwithin7calendardaysofinitialnotificationofthesignificant
deviation.DeviationswillbereportedbytheWRAIRHSPBtotheUSAMRDCORPHRPOas
perSOP-UWZ-C-636.
Non-emergent/minor deviations are routine departures that typically involve a participant’s
failuretocomplywiththeprotocol.Examplesincludemissingscheduledvisitsandfailingto
complete a required questionnaire. Minor deviations will be reported to the MUSPH IRB,
UNCST,andNDAinacumulativesummaryreportwiththeannualcontinuingreviewreportand
withthecloseoutreport.
11.2
SafetyReports
ThePIwillberesponsibleforforwardinganySafetyReportsissuedbythestudySponsortothe
MUSPHIRBandNDAinatimelymanner.
11.3
Pregnancies
Eachpregnancymustbereportedpromptly(within24hoursofidentification)bytelephoneor
emailto thePSRT.Pregnanciesmustbereported,within48hours ofbecomingawareofthe
event,totheWRAIRHSPB,theMUSPHIRB,andNDA.
11.4
StudyHolds
TheWRAIRHSPB,MUSPHIRB,andNDAwillbeimmediatelynotifiedifanystudypause
criteriaaremet,asdeterminedbythePSRTorSMC.TheWRAIRHSPBwillforwardallstudy-
holdreportstotheUSAMRDCORPHRPOasperSOP-UWZ-C-636.

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11.5
ProtocolModifications
AmendmentstotheprotocolwillbemadeonlyafterconsultationandagreementbetweenNIAID
VRC,theMHRPConsultants,andthePI.Allprotocolmodifications(includingbutnotlimited
tochangesinthe PI,inclusion/exclusioncriteria,numberofparticipantstobe enrolled,study
sites,orprocedures)mustbesubmittedasawrittenamendmenttotheMUSPHIRB,NDAand
U.S.FDAforreviewandapproval,andtotheWRAIRHSPBforassessmentofhumansubjects
determination/acknowledgment, beforeimplementationofthe changes.Submissions toethical
andregulatorycommitteeswillbemadeafterreviewandapprovalbytheINDMedicalOfficer
and the VRC IND Regulatory Representative. The WRAIR HSPB will submit any protocol
amendments and modifications that potentially increase the risk to subjects or others to the
USAMRDCORPHRPOforreviewandapprovalpriortoimplementation.
TheUNCSTshallbenotifiedofallMUSPHIRBapprovedprotocolamendments.
Modifications or updates to the Investigational Brochures (IBs) will also besubmittedto the
MUSPHIRB,NDA(asspecifiedabove),andWRAIRHSPBforacknowledgment.
The Informed Consent Form must be revised to concur with any significant amendment that
directlyaffectsparticipants,andmustalsobereviewedandapprovedwiththeamendment.New
participantsenrolledinthestudywillbeconsentedwiththemostrecentapprovedconsentform.
Participantsalreadyenrolledinthestudywillbeinformedabouttherevisionandaskedtore-
consent.Thismaybeaccomplishedbyrepeatingtheconsentprocesswiththerevisedconsent
formwithattentiongiventothechanges,orit maybedoneusing anaddendumconsent that
statestherevisionornewinformation.Thenewdocumentmustbesigned,placedinthestudy
record,andacopygiventotheparticipant.
Administrativechangestotheprotocolarecorrectionsand/orclarificationsthathavenoeffecton
thewaythestudyistobeconducted.SuchadministrativechangeswillbesubmittedtotheIRB
forreviewandapprovalpriortoimplementation.
11.6
ContinuingReviews/CloseoutReport
Acontinuingreviewreport(CRR)willbesubmittedtotheMUSPHIRBpriortotheanniversary
datedeterminedatinitialIRBreview.IfthecontinuingreviewisnotapprovedbytheMUSPH
IRBbytheanniversarydate,allprotocolactivitiesmuststopuntilsuchtimeastheapprovalis
obtained.
AcopyoftheCRRandCRRapprovalnotificationfromtheIRBofRecordwillbesubmittedto
theHRPOandtheUNCSTasthesedocumentsbecomeavailable.
After all study-relatedactivities,including dataanalysisare completed afinal/closeout report
will be submitted to the MUSPH IRB, UNCST and NDA. A copy of the approved closeout
report, including any acknowledgment documentation and supporting documents will be
submittedtotheWRAIRHSPBassoonasthesedocumentsbecomeavailable.Acloseoutreport
will be submitted after 5 years from study start or upon completion of the study, whichever
occursfirst.TheWRAIRHSPBwillforwardCRRapprovalnotificationsandcloseoutreportto
theUSAMRDCORPHRPOasperSOP-UWZ-C-636.

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UndercurrentUNCSTprocedure,aprotocolshallreceiveanapprovalforaperiodasmaybe
granted. Prior to expiration of that period, the PI will submit a request for extension of the
approvalwithrationale.
11.7 ReportingRequirementstotheMRDCORPHRPO
· Substantivemodificationstotheresearchprotocolandanymodificationsthatcould
potentiallyincreaserisktoparticipantsmustbesubmittedtotheHRPOforapprovalprior
toimplementation.TheUSAMRDCORPHRPOdefinesasubstantivemodificationasa
changeinPI,changeoradditionofaninstitution,eliminationoralterationoftheconsent
process,changeintheIRBofRecord,changetothestudypopulationthathasregulatory
implications(e.g.addingchildren,addingactivedutypopulation,etc.),significantchange
instudydesign(i.e.wouldpromptadditionalscientificreview)orachangethatcould
potentiallyincreaseriskstoparticipants.
· AnychangesoftheIRBusedtoreviewandapprovetheresearchwillbepromptlyreported
totheUSAMRDCORPHRPO.
· AcopyoftheIRBcontinuingreviewapprovallettermustbesubmittedtotheHRPOas
soonaspossibleafterreceiptofapproval.Forgreaterthanminimalriskresearch,acopyof
thecontinuingreviewreport,currentprotocolandconsentformattimeofcontinuing
reviewmustalsobeprovided.
· ThefinalstudyreportsubmittedtotheIRB,includingacopyofanyacknowledgement
documentationandanysupportingdocumentsmustbesubmittedtotheHRPOassoonas
alldocumentsbecomeavailable.
· ThefollowingstudyeventsmustbepromptlyreportedtotheHRPObytelephone
byemail
orby
facsimile
ormailtotheUSArmyMedicalResearchandMateriel
Command,ATTN:MCMR-RP

o Allunanticipatedproblemsinvolvingrisktosubjectsorothers.
o Suspensions,clinicalholds(voluntaryorinvoluntary),orterminationsofthis
researchbytheIRB,theinstitution,thesponsor,orregulatoryagencies.
o Anyinstancesofseriousorcontinuingnoncompliancewiththefederalregulations
orIRBrequirements.
o Theknowledgeofanypendingcomplianceinspection/visitbytheFoodandDrug
Administration(FDA),OfficeforHumanResearchProtections,orother
governmentagencyconcerningthisclinicalinvestigationorresearch.
o Theissuanceofinspectionreports,FDAForm483,warningletters,oractions
takenbyanygovernmentregulatoryagencies.
o Changeinparticipantstatuswhenapreviouslyenrolledhumanparticipant
becomesaprisonermustbepromptlyreportedtotheUSAMRDCORPHRPO.
ThereportmustincludeactionstakenbytheinstitutionandtheIRB.

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11.8
UseofInformationandPublication
It is expected that data from this study will be reported in both scientific journals and
internationalscientificmeetings.Confidentiality ofparticipantswillbemaintainedbythefact
that individual results will not be reported or published, only group/aggregate results. All
researchdatawillbeidentifiedbythestudynumber.Thelinkagebetweenpersonalidentifiers
andstudynumberwillonlybeavailableinaconfidentialsourcedocument/databaseatthestudy
site.Thelocalhealth authoritieswill beinformedof allscientificoutcomesofthe studyand
general prevalence and incidence data however, confidentiality will be maintained, and
participant identities will not be released. Only aggregate information will be released. All
publicationsresultingfromthisstudywillbeclearedthroughthecollaboratingpartnerstothis
study.
WRAIR recognizes the importance of communicating medical study data and therefore
encouragestheirpublicationinreputablescientificjournalsandatseminarsorconferences.Any
resultsofmedicalinvestigationsand/orpublication/lecture/manuscriptsbasedthereon,shallbe
exchangedanddiscussedbytheinvestigator,thesponsorrepresentative(s)andtheU.S.Army
Medical Research and Materiel Command 60 days prior to submission for publication or
presentation.
Resultsfrominvestigationsshallnotbemadeavailabletoanythirdpartybytheinvestigating
team outside the publication procedure as outlined previously. WRAIR will not quote from
publications by investigators inits scientific information and/or promotional material without
full acknowledgment of the source (i.e., author and reference). All publications written by
WRAIR investigators must be reviewed and approved by WRAIR Office of Research
TechnologyandApplications(ORTA).

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12.0
CONDUCTOFTHERESEARCHSTUDY
This research study will be conducted in accordance with ICH GCP guidelines, UNCST
guidelines,DOD Directive3216.2, theDeclarationofHelsinki, theBelmont Report,theU.S.
Code ofFederalRegulations21CFR 312,812,50 and56,andallapplicablelocal lawsand
regulations.
12.1
RegulatoryAudits
The knowledge ofany pendingcompliance inspection/visit by the USFDA, OHRP,or other
governmentagencyconcerningthisresearch,theissuanceofInspectionReports,FDAForm483,
warninglettersoractionstakenbyanyregulatoryagenciesincludinglegalormedicalactions
andanyinstancesofseriousorcontinuingnoncompliancewiththeregulationsorrequirements
willbereportedimmediatelytotheINDsponsor,WRAIRHSPB,NDAandMUSPHIRB.The
WRAIRHSPBwillreportknowledgeofanypendinginspections/auditsbyregulatoryagencies
totheUSAMRDCORPHRPO.
12.2
ProtocolMonitoringPlan
Sitevisits by the study monitor willinclude a review of thefollowing: study operations, the
qualityofdatacollectedintheresearchrecords,theaccuracyandtimelinessofdataenteredin
thedatabase,andtodeterminethatallprocessandregulatoryrequirementsaremet.
Siteinvestigatorswillallowthestudymonitors,representativesoftheVRCordesignee,WRAIR
HSPB,MUSPHIRB,NDA,UNCST,USAMRDCORPHRPO,andtheFDAtoinspectstudy
documents (e.g., consent forms, drug accountability and dispensing records, CRFs), and
pertinentclinicalrecordsforconfirmationofthestudydata.
Studydatawillbeclosedandfinalafterdatacleaningactivitiesarecompletedandresolutions
havebeendocumented.

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14.0
REFERENCES
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Virol,2013.158(1):p.301-11.
2.
Hart,M.K.,Vaccineresearcheffortsforfiloviruses.IntJParasitol,2003.33(5-6):p.583-
95.
3.
Sanchez,A.,etal.,SequenceanalysisoftheEbolavirusgenome:organization,genetic
elements,andcomparisonwiththegenomeofMarburgvirus.VirusRes,1993.29(3):p.
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4.
Sanchez,A.,etal.,SequenceanalysisoftheMarburgvirusnucleoproteingene:
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Virol,1992.73(Pt2):p.347-57.
5.
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http://www.who.int/mediacentre/factsheets/fs_marburg/en/.
7.
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Meslin,F.X.,Globalaspectsofemergingandpotentialzoonoses:aWHOperspective.
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Hensley,L.E.,etal.,EbolaandMarburgviruses:pathogenesisanddevelopmentof
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Sullivan,N.,Z.Y.Yang,andG.J.Nabel,Ebolaviruspathogenesis:implicationsfor
vaccinesandtherapies.JVirol,2003.77(18):p.9733-7.
12.
Dixon,M.G.,etal.,EbolaViralDiseaseOutbreak--WestAfrica,2014.MMWRMorb
MortalWklyRep,2014.63(25):p.548-51.
13.
WHO.EbolaSItuationReport-30March2016.2016[cited2016;Availablefrom:
https://apps.who.int/iris/bitstream/handle/10665/204714/ebolasitrep_30mar2016_eng.pdf.
14.
WHO.EbolaVirusDisease,DemocraticRepublicoftheCongo:ExternalSituation
Report#34-26March2019.2019[cited2019;Availablefrom:
https://apps.who.int/iris/bitstream/handle/10665/311507/SITREP_EVD_DRC_20190326-
eng.pdf.
15.
Ledgerwood,J.E.,N.J.Sullivan,andB.S.Graham,ChimpanzeeAdenovirusVectorEbola
Vaccine--PreliminaryReport.NEnglJMed,2015.373(8):p.776.
16.
Ewer,K.,etal.,AMonovalentChimpanzeeAdenovirusEbolaVaccineBoostedwith
MVA.NEnglJMed,2016.374(17):p.1635-46.
17.
Ledgerwood,J.E.,etal.,ChimpanzeeAdenovirusVectorEbolaVaccine.NEnglJMed,
2017.376(10):p.928-938.
18.
Stanley,D.A.,etal.,Chimpanzeeadenovirusvaccinegeneratesacuteanddurable
protectiveimmunityagainstebolaviruschallenge.NatMed,2014.
19.
Tapia,M.D.,etal.,UseofChAd3-EBO-ZEbolavirusvaccineinMalianandUSadults,
andboostingofMalianadultswithMVA-BN-Filo:aphase1,single-blind,randomised
trial,aphase1b,open-labelanddouble-blind,dose-escalationtrial,andanested,

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randomised,double-blind,placebo-controlledtrial.LancetInfectDis,2016.16(1):p.31-
42.
20.
Martin,J.E.,etal.,ADNAvaccineforEbolavirusissafeandimmunogenicinaphaseI
clinicaltrial.ClinVaccineImmunol,2006.13(11):p.1267-77.
21.
Ledgerwood,J.E.,etal.,AreplicationdefectiverecombinantAd5vaccineexpressing
EbolavirusGPissafeandimmunogenicinhealthyadults.Vaccine,2010.29(2):p.304-
13.
22.
Ledgerwood,J.E.,Enama,M.E.,Costner,P.,Hu,Z.,Hendel,C.S.,Sullivan,N.,Koup,
R.,Graham,B.S.,VRC206:PhaseIClinicalTrialofEbolaandMarburgDNAVaccines
inHealthyAdults,inNationalFoundationofInfectiousDiseases,15thAnnual
Conference.2012:Baltimore,MD..
23.
Sarwar,U.N.,etal.,SafetyandimmunogenicityofDNAvaccinesencodingEbolavirus
andMarburgviruswild-typeglycoproteinsinaphaseIclinicaltrial.JInfectDis,2015.
211(4):p.549-57.
24.
Kibuuka,H.,etal.,SafetyandimmunogenicityofEbolavirusandMarburgvirus
glycoproteinDNAvaccinesassessedseparatelyandconcomitantlyinhealthyUgandan
adults:aphase1b,randomised,double-blind,placebo-controlledclinicaltrial.Lancet,
2015.385(9977):p.1545-54.
25.
DeSantis,O.,etal.,Safetyandimmunogenicityofachimpanzeeadenovirus-vectored
Ebolavaccineinhealthyadults:arandomised,double-blind,placebo-controlled,dose-
finding,phase1/2astudy.LancetInfectDis,2016.16(3):p.311-20.
26.
Yang,Z.Y.,etal.,IdentificationoftheEbolavirusglycoproteinasthemainviral
determinantofvascularcellcytotoxicityandinjury.NatMed,2000.6(8):p.886-9.
27.
Sullivan,N.J.,etal.,ImmuneprotectionofnonhumanprimatesagainstEbolaviruswith
singlelow-doseadenovirusvectorsencodingmodifiedGPs.PLoSMed,2006.3(6):p.
e177.
28.
Barnes,E.,etal.,Noveladenovirus-basedvaccinesinducebroadandsustainedTcell
responsestoHCVinman.SciTranslMed,2012.4(115):p.115ra1.
29.
O'Hara,G.A.,etal.,ClinicalassessmentofarecombinantsimianadenovirusChAd63:a
potentnewvaccinevector.JInfectDis,2012.205(5):p.772-81.
30.
Colloca,S.,etal.,Vaccinevectorsderivedfromalargecollectionofsimianadenoviruses
inducepotentcellularimmunityacrossmultiplespecies.SciTranslMed,2012.4(115):p.
115ra2.
31.
Peruzzi,D.,etal.,Anovelchimpanzeeserotype-basedadenoviralvectorasdeliverytool
forcancervaccines.Vaccine,2009.27(9):p.1293-300.
32.
Quinn,K.M.,etal.,Comparativeanalysisofthemagnitude,quality,phenotype,and
protectivecapacityofsimianimmunodeficiencyvirusgag-specificCD8+Tcells
followinghuman-,simian-,andchimpanzee-derivedrecombinantadenoviralvector
immunization.JImmunol,2013.190(6):p.2720-35.
33.
Helms,T.,etal.,Directvisualizationofcytokine-producingrecallantigen-specificCD4
memoryTcellsinhealthyindividualsandHIVpatients.JImmunol,2000.164(7):p.
3723-32.
34.
Dixon,M.G.andI.J.Schafer,EbolaVirusDiseaseOutbreak-WestAfrica,2014.
Morbidityandmortalityweeklyreport,2014.63:p.1-4.
35.
Betts,M.R.,J.P.Casazza,andR.A.Koup,MonitoringHIV-specificCD8+Tcell
responsesbyintracellularcytokineproduction.ImmunolLett,2001.79(1-2):p.117-25.


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APPENDIX1:SCHEDULEOFEVALUATIONS



RV 508/WRAIR #2439 
 
Version 1.5 
Schedule of Evaluations 
 
03 March 2020 
 
RV 508 Schedule of Evaluations 
Visit 
 
01 
02 
02A 
02B 
02C 
02D 
03 
04 
05 
06 
07 
Week of Study 
 
-8 to 0 
W 0 
W 1 
W 1 
W1 
W2 
W4 
W 8 
W 16 
W 24 
W 48 
Day of Study 
 
-56 to 0 
D 0 
D 1 
D 3 
D 7 
D14 
D 28 
D 56 
D 112 
D 168 
D 336 
Clinical Evaluations 
Tube 
Screening1 
Enrollment 
 
 
 
 
 
 
 
 
 
Informed Consent, Assessment of 
Understanding 
 
X 
 
 
 
 
 
 
 
 
 
 
Physical exam and weight at screen;  
Vital signs, targeted exam at other visits 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Medical history for eligibility at screen; 
interim history other visits 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Study Vaccination2 
 
 
X 
 
 
 
 
 
 
 
 
 
Begin/Review 7-Day Diary Card6 
 
 
X 
 
X 
X 
X 
 
 
 
 
 
Telephone contact; clinic visit if 
indicated 
 
 
 
X 
 
 
 
 
 
 
 
 
Counseling on pregnancy prevention 
 
 
X 
 
 
 
X 
X 
X 
X 
 
 
CBC w/total lymphocyte count 
Anti-coagulant 
3 
3 
 
3 
 
3 
3 
3 
 
3 
 
Pregnancy test: urine (or serum)3 
 
X 
X 
 
 
 
 
X 
 
 
X 
 
Creatinine and ALT 
Coagulant 
4 
4 
 
4 
 
4 
4 
4 
 
 
 
HIV5 and RPR 
 
6 
 
 
 
 
 
 
 
 
 
 
Research Immunology 
 
 
 
 
 
 
 
 
 
 
 
 
Serum storage for antibody assays 
Coagulant 
12 
12 
 
12 
12 
12 
12 
12 
12 
12 
12 
Pre-Existing Vector Immunity testing 
 
X 
 
 
 
 
 
 
 
 
 
 
PBMC and plasma for storage 
Anti-coagulant 
8.5 
68 
 
 
59.5 
42.5 
59.5 
42.5 
59.5 
76.5 
76.5 
Intracellular RNA 
PAXgene 
 
3 
 
6 
6 
 
 
 
 
 
 
HLA type4 
Anti-coagulant 
 
 
 
 
 
 
 
 
17 
 
 
Daily Volume (mL) 
 
33.5 
90 
0 
25 
77.5 
61.5 
78.5 
61.5 
88.5 
91.5 
88.5 
Max. Cumulative Volume (mL) 
 
33.5 
123.5 
123.5 
148.5 
226 
287.5 
366 
427.5 
516 
607.5 
696 
Visit windows: 02A (+1 day); 02B (+2 days); 02C (+3 days); Visit 02D (±3 days); Visits 03 and 04 (±7 days); Visits 05, 06 and 07 (±14 days). 
1 Most screening evaluations must be no more than 56 days prior to Day 0 to be used for eligibility (pregnancy test from Day 0 must be used for eligibility). If clinical 
assessment on Day 0 suggests significant changes may have occurred since screening, then physical examination & laboratory studies done on Day 0 are used for eligibility. 
Day 0=day of enrollment and vaccine injection. Day 0 evaluations prior to first injection are the baseline for assessing adverse events subsequently. 
2 Complete post vaccination vitals and injection site assessment after the study injection (target to complete this within the interval 30 to 45 minutes post-
vaccination). Subjects must remain in the clinic for at least 30 to 60 minutes after injection.  
3 Negative pregnancy test results must be confirmed for women of reproductive potential prior to administering the vaccine injection. Serum pregnancy testing at 
screening visit, urine pregnancy testing at enrollment visit and all follow-up visits where indicated. Serum taken from blood collected for HIV and RPR tests. 
4 HLA type blood sample is collected once at any time point in the study and is shown as a Visit 05 evaluation for convenience; however, if HLA type is already 
available in the medical record it does not need to be repeated. HLA type may also be obtained from a frozen sample. 
5 Includes pre/post-test counseling as per site SOP 
6 The Diary Card can be collected at any time between Visit 02C and Visit 02D (to include at an unscheduled visit) in order to obtain a complete day 7 
assessment of any solicited symptoms. 

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APPENDIX2:INFORMEDCONSENTFORMS

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APPENDIX2A:MAININFORMEDCONSENTFORM
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RV 508/WRAIR #2439 
 
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MAIN STUDY INFORMED CONSENT FORM 
 
Study Title:  RV 508, “A Phase I Open-Label, Dose-Escalation Clinical Trial to Evaluate the Safety, 
Tolerability and Immunogenicity of Two Doses of an Ebola Sudan Chimpanzee 
Adenovirus Vector Vaccine, VRC-EBOADC086-00-VP (cAd3-EBO S), in Healthy 
Adults” 
Sponsor: National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases 
(NIAID) Vaccine Research Center (VRC) 
Funding Agencies: NIH, the U.S. Military HIV Research Program (MHRP) and the U.S. Department of 
Defense (DoD) 
Study Product Provided by: NIH/NIAID/VRC 
Study Conducted by: Makerere University Walter Reed Project (MUWRP) 
Principal Investigator: Betty Mwesigwa, MBChB, MSc Clinical Trials 
INTRODUCTION 
You are being invited to consider participating in this study because you are a healthy person who may 
meet the criteria to join this study. Before deciding to participate in this study, please read this document 
thoroughly. In doing so, you will understand the purpose and details of this study.  
Before you decide whether or not to take part in this study, we would like to explain the purpose of the 
research study, how it may help you or others, any risks associated with participation, and our 
expectations of you. This process is called informed consent. It is important that you know the 
following: 
a. Taking part is of your own free will (entirely voluntary). 
b. If you decide not to participate you will not lose any of the benefits or rights you would normally 
have or be disadvantaged in any way. 
c. You may decide not to participate in the study or you may decide to stop participating in the 
study at any time without loss of any medical care to which you are entitled now or in the future.  
Please ask questions about anything you do not understand at any time. The clinic staff will talk to you 
about the information in this form. You can take as much time as you need to review this form and 
discuss your study participation with your family, friends, and community as you feel comfortable and 
appropriate, in order to decide whether or not you would like to participate. If you decide to participate 
in this study, you will review this document with a study staff and will be requested to sign and date at 
the end of this form to show that your questions have been answered and that you want to take part in 
the study. A copy of this signed/marked informed consent will be provided to you. This consent must be 
signed/marked before any study procedures are performed. 

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You will also have the opportunity to consent for future (currently unknown) use of your samples, and 
genetic testing. These will be explained to you, and you will sign a separate consent for each. 
The technical name of the study vaccine is VRC-EBOADC086-00-VP, but we will refer to it as “cAd3-
EBO S” or simply as the “Ebola vaccine.” The study vaccine does not contain live or killed Ebola virus. 
It is impossible for the study vaccine to give you an Ebola virus infection. 
This research study is funded by the U.S DoD and the NIAID/NIH. The MUWRP is conducting this 
research study in collaboration with the U.S. MHRP and NIAID/NIH in Kampala, Uganda.  
PURPOSE AND BACKGROUND 
This research study will evaluate an experimental vaccine for the Ebola Virus. “Experimental” means 
that it is not known if the vaccine works to prevent the Sudan strain of Ebola Virus Disease (EVD). 
Since it is not known if the vaccine works, it has not been approved by the US Food and Drug 
Administration (FDA) or the Uganda National Drug Authority (NDA). Vaccines are substances used to 
create immune responses (resistance) to an infection in order to prevent a disease. Immune responses are 
how your body recognizes and defends itself against bacteria, viruses, and substances that may be 
harmful to the body.  
The main purpose of this study is to see if the experimental Ebola vaccine is safe and if it causes any 
side effects. Another goal is to study blood samples in the lab to see if and how the immune system 
responds in people who receive this vaccine.  
The Ebola virus was discovered in 1976. It is named after a river in Africa close to where the virus was 
first discovered. Bats in certain parts of Africa carry the virus. EVD starts with fever and muscle aches. 
More severe symptoms are breathing problems, severe bleeding, kidney problems, and shock (loss of 
blood pressure). The infection may be mild, but it can also lead to death. The first two outbreaks of 
Ebola Hemorrhagic Fever in Africa in 1976 caused 340 deaths. In Africa, when there have been 
outbreaks of Ebola virus, 50% to 90% of infected people have died.  
STUDY VACCINE 
The experimental Ebola vaccine in this study was developed in a laboratory by the VRC at the NIH, 
located in Bethesda, Maryland USA. The experimental vaccine has previously been given to humans in 
combination with other Ebola vaccine products, but not by itself. 
The cAd3-EBO S vaccine uses another virus, called chimpanzee Adenovirus 3 (cAd3), to deliver a piece 
of the Ebola Sudan virus to cells in your body. The adenovirus used to make the vaccine is from a strain 
that infects chimpanzees. This strain of adenovirus has been tested in people before and does not cause 
human adenovirus infections. It is further changed to make sure it cannot reproduce in a human body.  
Once the Ebola Sudan virus piece is delivered to the cells in your body, your body will then make an 
immune response. You cannot become infected with or infect someone else with either Ebola or 
adenovirus from receiving the study vaccine. 

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STUDY PARTICIPATION 
If you agree to take part in the study you will receive one study injection at the enrollment visit (Visit 2). 
The vaccine injection will be given using a needle and syringe into an upper arm muscle. This is called 
an intramuscular (IM) injection. 
About 40 participants will be enrolled into this study and will be divided into 2 groups. Both groups will 
have about 20 participants. Participants in Group 1 will receive a low dose of the vaccine and 
participants in Group 2 will receive a higher dose. Enrollment into Group 2 will not begin until after a 
safety review is completed for participants who received the lower dose of the vaccine and it is 
determined to be safe. The higher dose of the experimental Ebola Sudan vaccine is based on dose levels 
found to be safe in previous studies of similar vaccines that used the chimpanzee adenovirus. If you 
would like to know which group you are in, please ask the study clinician. 
Vaccination Schedule: 
RV 508 Study Groups 
Group 
Participants 
Vaccine Dose 
1 
20 
cAd3-EBO S at 1x1010 PU IM 
2 
20 
cAd3-EBO S at 1x1011 PU IM 
STUDY DURATION 
Participation in this study will last for about 48 weeks (almost 1 year) from the time of enrollment. 
There will be 1 screening visit and 10 study visits (1 visit for vaccination and 9 visits for follow-up). 
However, these do not include additional appointments if you have any side effects and if the study team 
requests you to come to the clinic. The screening and vaccination visits will each take approximately 2-3 
hours. Other appointments will take approximately 1-2 hours. A schedule of events detailing your visits 
will be provided to you. 
STUDY PROCEDURES 
a) How do I join in this study? 
You will have to sign this form acknowledging that you have read the form, that all your questions have 
been answered satisfactorily, and that you agree to participate in this study.  
You may take part in this study if you are a healthy, male or female volunteer, between ages 18 and 50 
with a body mass index (a ratio based on your weight and height) < 40, available for a period of 48 
weeks, able to provide proof of identity, willing to have the vaccine injection site and any vaccine 
reactions on your skin photographed, and agree to clinic staff visiting your home (as may be necessary). 
You must also be able to read this consent form, understand and complete this informed consent process, 
successfully complete an Assessment of Understanding (to see if you understand the information in this 
form), and be free of significant medical problems. Blood tests will be done to measure your 
hemoglobin (amount of blood), your white blood cells, and your liver and kidney function. Females will 
also be required to undergo pregnancy testing, to not be pregnant, to not be breastfeeding, and to plan 
not to become pregnant for at least 6 months after vaccination. Females must also agree to use a birth 
control method for at least 21 days prior to vaccination and for at least 6 months after vaccination.  

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You cannot participate in this study if you received an experimental Ebola or Marburg vaccine or have 
received a different cAd3 experimental vaccine. You also cannot participate if you have any of the 
following conditions:  
• A history of a serious allergic reaction to any vaccines or allergic reaction to drugs like 
gentamycin, neomycin or streptomycin 
• An autoimmune disease or deficiency or chronically recurring hives, asplenia (lack of normal 
spleen function) or a history of angioedema (facial swelling) 
• HIV infection 
• Active syphilis infection 
• Diabetes (type I or II) 
• Thyroid disease that is not well controlled 
• High blood pressure or asthma that is not well controlled 
• A bleeding problem or disorder 
• Cancer 
• A history of seizures or treatment for seizure disorder in the past 3 years 
You also cannot participate if you have received any of the following: 
• Drugs that may modify your immune system within 14 days prior to enrollment such as 
prednisone or dexamethasone 
• Blood products within 112 days (16 weeks) prior to enrollment 
• Any “live-attenuated” vaccine (e.g., oral polio, yellow fever, measles, etc.) within 28 days prior 
to enrollment in the present study or any other vaccine within 14 days prior to enrollment 
• Experimental research drugs within 28 days prior to enrollment in the present study 
• Drugs for treating or preventing Tuberculosis 
 
You also may not participate in the study if the Investigators think you may have a history of any 
condition(s) that may interfere with your full participation in the study or that may impair your ability to 
provide informed consent. 
It is important to remind you that to participate in this study you need to agree to home visits by the 
clinic staff. The clinic staff may visit your home if they are unable to reach you by phone, in order to 
remind you of your scheduled visit or for follow up.  
b) Screening (Visit 1) 
After you have reviewed the study consent form and have agreed to participate, the study staff will ask 
you to complete an Assessment of Understanding (AOU). The AOU will help the study staff to 
determine how well you have understood the information about this study and what is required for 
participation. You must complete 9 out of the 10 questions correctly at least once in 3 attempts. After the 
AOU, your medical history will be recorded and a thorough physical examination will be performed on 
you by a member of the study staff. In addition, you will have blood taken to check your HIV and 
syphilis status.  
A serum (blood) pregnancy test will be required at the screening visit if you are female and able to 
become pregnant. The research staff will test your blood for HIV (human immunodeficiency virus), the 

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virus that causes AIDS. Prior to this blood test, you will receive counseling about HIV, AIDS, and 
prevention of HIV. If you are HIV infected, you will receive additional information about HIV and will 
be referred to our HIV Clinic or the Infectious Disease Institute (IDI) at Mulago or any other HIV Clinic 
of your choice.  
It may be necessary to return to the clinic for a follow up appointment or to repeat tests if there are any 
abnormal laboratory results. If the physician discovers an illness or condition that requires treatment, 
you will be referred to a hospital or clinic that can provide further evaluation or treatment. 
If you are eligible for participation in this study, you will be scheduled for an appointment for the 
vaccination visit within 56 days of the screening date. It is important to remind you that as part of the 
qualification for this study you have agreed to possible home visits by the clinic staff.  
c) Enrollment and Follow-up Visits 
The clinic staff will observe you for at least 30 to 60 minutes after the injection at the enrollment visit.  
You will be asked to complete a diary card and look at your injection site in the evening on the day of 
the vaccination and then every day for the next 7 days. You will record your temperature, any 
symptoms, and describe any skin changes at the injection site each day. You will be provided with a 
thermometer to take your temperature and ruler to measure any injection-site skin changes. You may 
have to come to the clinic if you have a fever of 38.5˚C or higher that lasts more than 24 hours, a rash, 
hives, or difficulty in your usual daily activities (such as going to work, fixing a meal, laundry, etc.). 
You will be able to reach a study investigator at any time of day or night should you have any concerns.  
If you develop any symptoms that are of concern to you or the study team, it may be necessary to come 
to the study clinic for an examination before your next scheduled visit. It is very important that you 
follow the instructions given to you by the clinic staff. You may also need to come to the clinic for any 
problem that the nurse or doctor thinks should be checked by exam, blood or other medical test. 
At each visit, you will be checked for any health changes or problems since your last visit. You will be 
asked how you are feeling and what medications you may have taken. Blood will be drawn during clinic 
visits for testing of your health and your immune system.  
The amount of blood drawn will vary from about 25 mL (about 5 teaspoons) to about 92 mL (6 
tablespoons), depending on the visit. You might also be asked to have laboratory tests between regular 
visits if needed to check your health. The total amount of blood drawn during the 48 weeks of 
participation will be less than 700 mL (about 1.5 tumpeco mugs). 
No more than a total of about one tumpeco mug (450 mL) will be drawn over any 3-month period during 
the study. Female participants will also have to give a urine sample for pregnancy test at some visits. 
You will be informed promptly if any health concerns are identified by the tests. You should avoid 
donating blood for at least one year after your study vaccination. 
The study team will inform you of the results from your lab tests and medical examination at the next 
study visit. In cases where an abnormality may be of concern, the investigators will notify you as soon 
as possible. If any concerning abnormality is detected, you will be referred for appropriate testing, 
treatment and care as may be required. 

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d) Sample collection during the study 
i. 
Blood and urine specimens: The investigators will obtain blood to test for any possible side 
effects as well as evaluate the immune response to the vaccine. Urine collected at study 
visits will be used for pregnancy tests for female volunteers.  
 
ii. 
HLA and genetic tests: Part of the blood samples for this study will be used to analyze for 
HLA (‘Human Leukocyte Antigen’) type. HLA is a group of proteins present on the surface 
of all cells in the human body with an important role in the immune response to infection. 
Determining HLA type is necessary to be able to perform certain research studies. We will 
not notify you with the results of this test. The HLA test for this study is not a normal 
medical test and the test result will not be used for treatment purpose. You will be provided a 
separate form to consent or refuse genetic testing on your samples. 
WHAT WILL HAPPEN TO MY SAMPLES AFTER THIS STUDY? 
a) Sample Storage 
During your participation in this study, blood samples will be collected from you as already 
explained. We will store left over blood samples in a secure central storage site (not in the 
clinic) in the USA for future research to learn more about Ebola virus, vaccines, the immune 
system, and/or other medical conditions. Only samples from participants who have provided 
consent for future use of their samples will be stored at the end of this study. If consent is not 
provided, the samples will be destroyed upon completion of tests for this study. 
Please note that samples will only be transferred to another country after approval by the 
Uganda National Council of Science and Technology and your personal information will not 
be disclosed/ attached to these specimens (as described below). 
b) Future Studies  
You will have the opportunity to review, ask questions and provide consent (permission) for 
storage and use of your blood samples for future unknown use, in the “Future Use Blood 
Sample Consent Form.” All future research that uses stored samples must be reviewed and 
approved by an Institutional Review Board (IRB), which is a committee that is responsible 
for overseeing the safety, welfare and rights of research participants. 
c) Specimen Labeling 
Specimens will be stored and labeled using a numeric barcode without your name attached. 
Only the site-investigator team is able to connect those numeric codes and your name. 
Personal Identification Information will be kept confidentially according to all applicable 
laws and regulations.
POSSIBLE RISKS OF STUDY PARTICIPATION 
This section describes the risks associated with the experimental Ebola Sudan vaccine and other study 
procedures. There may be additional risks related to the experimental vaccine that are currently 
unknown. These unknown risks could affect you or, if applicable, your unborn child if you become 
pregnant. If the study investigators learn about new risks during this study, the study investigators will 
tell you. 

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Possible risks from the injection: Temporary stinging, pain, arm discomfort, redness, soreness, 
itchiness, swelling or bruising at the injection site on your arm. There is a very small chance of 
infection. 
Possible risks from any vaccine: Fever, chills, rash, aches and pains, nausea, headache, dizziness, 
fatigue (feeling tired), and malaise (feeling unwell). Some people have allergic reactions to vaccines. 
These types of reactions are usually greatest within the first 24 hours after vaccination and may last 1 to 
3 days.  
Possible risks of the experimental Ebola Sudan vaccine: The risks of the experimental vaccine are 
unknown. The most common complaints in the first few days after receiving similar vaccines include 
sore arm, headache, muscle aches and feeling tired. A few people had a fever within a day after 
vaccination.  
As with any vaccine, there may be a risk of skin rash, hives, or other unknown side effects. If you 
develop a reaction to the experimental vaccine on your skin, the investigators will take pictures of the 
reaction and the vaccine injection site. Every effort will be made to avoid photographing your face or 
any tattoos or birthmarks that may identify you in the photograph. Your name and other identifying 
information will not be associated with the photograph. All photographs will relate only to this study 
and will be the property of the sponsor. 
There are currently no vaccines approved for use to protect against Ebola virus infection. Receipt of this 
experimental Ebola vaccine may affect your response to future vaccines against Ebola. It is unknown if 
you will develop an immune response, such as antibodies, after vaccination. It is unknown if your 
immune response would protect against EVD, have no effect on protection, or increase your risk of 
EVD. It is also unknown how long an immune response to the vaccine may last. You should continue to 
take all precautions against being exposed to body fluids of people who have an Ebola virus infection. 
Unknown safety risks: There may be unknown side effects from the study vaccine – even serious or 
life-threatening risks – that we do not yet know about. Please tell the study staff about any side effect 
you think you are having as soon as possible. This is important for your safety. 
Possible risks of blood drawing: Pain, bleeding, bruising, feeling lightheaded, fainting, or rarely, 
infection at the site where the blood is taken. To minimize the risks, trained health care providers will 
draw your blood. 
Possible risks from genetic testing: Unintended release of information could be used by insurers or 
employers; discovering a gene that suggests risk of disease for you or your family; discovering 
undisclosed family relationships. To minimize the risks, results will only be labeled with a code, not 
your name or other identifying information. 
Possible risks to Pregnancy: If you are pregnant, breast-feeding or want to become pregnant from 21 
days before vaccination until 24 weeks (6 months) after the vaccination, you cannot participate in this 
study. We do not know the possible effects of the study vaccine on the unborn baby or nursing infant. 
Therefore, women who are able to become pregnant must have a negative pregnancy test before the 
study vaccination and agree to practice adequate birth control beginning at least 21 days prior to 
receiving the study injection until 24 weeks after the injection. Adequate methods of birth control 
include: condoms, male or female, with or without a spermicide; diaphragm or cervical cap with 

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spermicide; intrauterine device; all prescription methods (such as contraceptive pills, injections, patches 
and others); or a male partner who has previously undergone a vasectomy. You must notify the clinic 
staff immediately upon learning that you have become pregnant during this study. You must also notify 
the clinic if you suspect that you might be pregnant during this study. You will be asked to continue 
with the planned study follow-up visits for safety purposes and contacted later to learn about the 
outcome of any pregnancy that starts in the first 24 weeks after study vaccination. 
Other Risks: You may not donate blood while participating in this research study or for one year after 
the date of the experimental vaccine injection.  
Your samples will be shipped to collaborators outside of MUWRP to be analyzed. These samples will 
only be labeled with your study number, not your name or other personal information. Samples will only 
be shipped after approval from the MUWRP IRB. 
WHAT IF THE RESEARCHERS LEARN NEW INFORMATION DURING THIS STUDY? 
Results of this study or other scientific research may affect your willingness to continue to take part in 
this study. During the course of the study, you will be informed of any significant new findings (either 
good or bad), such as changes in the risks or benefits resulting from participation in the research or new 
alternatives to participation that might cause you to change your mind about continuing in the study. If 
new information is provided to you, your consent to continue participating in this study will be re-
obtained. 
BENEFITS FROM STUDY PARTICIPATION 
You will receive no direct benefit from participating in this study because no one knows if the vaccine 
will work. However, you and others may benefit in the future from the information that will be learned 
from the study. The results of this study could play a role in whether the FDA will approve the vaccine 
for sale at some time in the future. You will not receive money or other compensation should this occur. 
COMPENSATION FOR STUDY PARTICIPATION 
You will be compensated Ug shs 50,000 for time and inconvenience associated with each scheduled 
visit and up to Ug shs 20,000 for each unscheduled visit. Unscheduled visits will be compensated only if 
the Principal Investigator/ designee finds it necessary. Other than medical care that may be provided and 
other payment specifically stated in this form, there is no other compensation available for you taking 
part in this study. 
PERSONAL INFORMATION CONFIDENTIALITY 
The Principal Investigator at this clinic, Dr. Betty Mwesigwa, will maintain research records of your 
taking part in this study. 
All study volunteers will receive a study identification (SID) number. An SID is a unique number 
assigned to each participant, known only to the study team at the clinic and used to ensure the 
confidentiality of research information. All your study documents, samples and test results will not bear 
your name but will have your SID, the date, study number, group number and study visit number. 
Personal identifying information like your name and age collected at the time of enrollment will be 

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stored in a lockable cabinet to which only designated study team members will have access. These steps 
will ensure confidentiality of your personal information and minimize the chances of it becoming known 
to others. 
Clinical and research records may be reviewed by representatives of the U.S. Army Medical Research 
and Development Command (USAMRDC), Office for Human Research Protections (OHRP), Human 
Research Protection Office (HRPO), U.S. DoD, WRAIR Human Subjects Protection Branch, Makerere 
University School of Public Health IRB, NIAID, the Uganda National Drug Authority (NDA), the 
Uganda National Council of Science and Technology, U.S. Food and Drug Administration, the Uganda 
Ministry of Health, and other agencies as part of their responsibilities for ensuring the protection of 
research volunteers. Representatives of all the above are bound by rules of confidentiality not to reveal 
your identity to others.  
Complete confidentiality cannot be promised but every effort will be made to keep the records as 
confidential as possible within the limits of the law. All data and medical information obtained about 
you as an individual will be considered important and held in confidence.  
Research and clinical information relating to you will be shared with other investigators and the 
scientific community through presentation or publication; however, you will not be identified by name 
or other personal information that could be used to identify you.  
General clinical trial information will be kept in the database at the National Medical Library at the 
National Institutes of Health on http://www.clinicaltrials.gov. This website will not include information 
that can identify you. At most, the Web site will include a summary of the results. 
SICKNESS OR INJURY AS A RESULT OF STUDY PARTICIPATION  
If you get sick or injured due to the vaccination of this study, you will receive appropriate medical 
treatment and care until cure or stabilization as provided for by a limited fund (set aside for this study) 
and a clinical trials medical insurance policy for research-related injuries. While we anticipate the 
combination of the set-aside fund and the insurance policy is more than enough to pay for the costs 
associated with any study related injuries, there is a limit to the amount of coverage available. The study 
sponsor, MUWRP, and the U.S. DoD will not provide long-term medical care for stabilized research-
related injuries. 
The study team is responsible for the cost without using any personal health care package which belongs 
to the volunteer. MUWRP will pay costs up to the limit from set aside finds or through the insurance. 
However, you will not get any other compensation. You should discuss this thoroughly with the 
Principal Investigator or site clinicians before making a decision to participate in this study. If you have 
any questions about study-related sickness or injury, you can contact the following person: 
Dr. Betty Mwesigwa 
Makerere University Walter Reed Project 
Kampala, Uganda 

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ENDING STUDY PARTICIPATION 
You can choose not to participate or withdraw from the study at any time without any consequence to 
you. Although you may withdraw from the study at any time, the samples and data collected up to that 
time will be used in accordance with the protocol. 
If you would like to withdraw from this study, please contact the Principal Investigator mentioned 
above. You will not lose any legal rights, including the rights for medical treatment and others if you 
withdraw from this study.  
Although you may be willing to participate in the study, the investigators may not give you the 
vaccination if any of the following situations occur: 
o Study is stopped. 
o Study sponsors, the IRBs, the US FDA or the Uganda NDA request to terminate the 
study for unexpected reasons. 
o You are unable to comply with the study requirements. 
o You are not willing to have blood drawn although you are still willing to participate in 
other processes. 
o You have a medical problem where continuing to be in the study would be harmful to 
you. 
o Other incidents occurred and may be harmful to you if you continue being the study 
volunteer. 
ALTERNATIVES 
This study is not designed to treat any disease and no alternative currently exists. You may choose to not 
participate. 
CONFLICT OF INTEREST STATEMENT 
The NIH, including members of the VRC scientific staff, developed the experimental Ebola vaccine 
being used in this research study. The results of this study could play a role in whether the FDA will 
approve the vaccine for sale at some time in the future. If approved, the future sale of the vaccine could 
lead to payments to the NIH and to some of the NIH/VRC scientists. By US Law, government scientists 
are required to receive such payment for their inventions. Other participating investigators do not have a 
conflict of interest as a result of study participation. You will not receive money or other compensation 
should this occur. Please discuss with a study investigator any questions you may have about these 
issues. There is no conflict of interest with your doctors at this research site. 
IF YOU NEED MORE INFORMATION OR HAVE ADDITIONAL QUESTIONS 
If you have any question about this study or if you have any problems, you can contact the Principal 
Investigator Dr. Betty Mwesigwa at the research clinic on 
or by telephone 
or toll free on 
or Immaculate Nakabuye on 
or 
 

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If you have any question and need to ask about your rights or you do not get appropriate treatment and 
care for sickness or injury which occur as a direct result of taking part in this study or the investigator 
does not treat you fairly in accordance with what is described in this consent form, you may make a 
complaint to the following bodies: 
For information on 
 
Regulatory questions 
The Executive Secretary, at Uganda National Council of Science and 
Technology, 
Kampala or on Tel number 
Human subject protection 
questions 
Dr. Suzanne Kiwanuka at the Research and Ethics Committee, Makerere 
University School of Public Health, Mulago Hospital Complex or on 
 
  
 
Please keep a copy of this document in case you want to read it again. 

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STUDY VOLUNTEER STATEMENT 
I have been asked to take part in RV 508, “A Phase I Open-Label, Dose-Escalation Clinical Trial to 
Evaluate the Safety, Tolerability and Immunogenicity of Two Doses of an Ebola Sudan Chimpanzee 
Adenovirus Vector Vaccine, VRC-EBOADC086-00-VP (cAd3-EBO S), in Healthy Adults”. 
The principal investigator Dr. Betty Mwesigwa or her representative has explained the significance of 
the testing, the duration of the study, the testing that I will undergo, the methods to be used, and the risks 
and dangers of participation. I have been given a chance to ask questions about this research study. All 
questions were answered to my satisfaction. If I have other questions about this research, I can ask: Dr. 
Betty Mwesigwa or Immaculate Nakabuye at the research clinic on 
or by 
telephone 
or toll free on 
 
I am signing below to indicate I wish to take part in this study, and my consent to follow the 
requirements of the study as much as possible. I will do my best to follow the recommendations of the 
study team, and I will report all problems occurring from this study to the study team. It has been 
explained to me that I can quit this study at any time, and I will not lose any benefits nor will I receive 
any penalty. If I decide to quit this study, I may be examined before leaving the study to ensure my good 
health. The medical care that I could receive as a result of sickness from being a part of this study have 
been explained to me and I have been offered a signed copy of this consent form. 
I agree to participate in this study. 
 
_________________________________________________ 
 ___________ 
SIGNATURE OR MARK OF PARTICIPANT 
DATE 
 
 
_______________________________________________________ 
PRINT NAME OF PARTICIPANT 
 
 
_________________________________________________ 
 ___________ 
SIGNATURE OF PERSON ADMINISTERING CONSENT 
DATE 
 
 
_______________________________________________________ 
PRINT NAME OF PERSON ADMINISTERING CONSENT 

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APPENDIX2B:FUTUREUSEINFORMEDCONSENTFORM
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INFORMED CONSENT FOR FUTURE USE OF STORED SPECIMENS 
 
Study Title:  RV 508, “A Phase I Open-Label, Dose-Escalation Clinical Trial to Evaluate the Safety, 
Tolerability and Immunogenicity of Two Doses of an Ebola Sudan Chimpanzee 
Adenovirus Vector Vaccine, VRC-EBOADC086-00-VP (cAd3-EBO S), in Healthy 
Adults” 
Sponsor: National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases 
(NIAID) Vaccine Research Center (VRC) 
Funding Agencies: NIH, the U.S. Military HIV Research Program (MHRP) and the U.S. Department of 
Defense (DoD) 
Study Product Provided by: NIH/NIAID/VRC 
Study Conducted by: Makerere University Walter Reed Project (MUWRP) 
Principal Investigator: Betty Mwesigwa, MBChB, MSc Clinical Trials 
 
During this study, you will be asked to provide blood. These blood samples will be stored for as long as 
possible and will be used according to your decision below. The blood samples will be stored in the 
United States (U.S.) for testing how your body fights Ebola infection and other future studies that we do 
not know about at this time. Some of the tests that may be conducted on your stored samples may not be 
developed yet, so the investigators cannot tell you all the tests that may be performed in the future.  
There is a chance that the blood samples you are donating under this study may be used in other research 
studies and may have some commercial value. Your samples will not be sold or used directly to produce 
commercial products.  
Should your donated sample(s) lead to the development of a commercial product, the study sponsor and 
inventor will own it and may take action to patent and license the product. Neither the sponsor nor the 
inventor intend to provide you with any compensation for your blood samples provided in this study, nor 
for any future value that the sample you have given may be found to have.  
The blood samples will not be stored with any personal information. Your stored samples will be labeled 
by a code (such as a number) that only the study team can link to you. All personal information will be 
stored by the study investigator at the study site. Any identifying information about you will be kept 
confidential to the extent permitted by law.  
You will not receive the results of future studies or future genetic tests involving your stored blood 
samples. The results of genetic tests will be for research purposes only. The genetic tests are not used in 
medical practice and have not been approved for use in making health care decisions. 
Future Research on Your Samples Will Be Related to Ebola or Vaccines 
Researchers are able to measure how the immune system responds by looking at blood samples. We will 
try to understand why Ebola disease progresses differently in some people. As new methods (or ways) 
of measuring the body’s immune response to Ebola are made in the laboratory, we would like to test 
these methods on the samples we have already collected from you. We also know that sometimes genes, 

RV 508/WRAIR #2439 
 
Version 1.5 
Future Use ICF 
Page 2 of 3 
03 March 2020 
passed down from your parents, can be important to a person’s immune response to Ebola. Because of 
this, we may do genetic testing on your stored samples. We may use methods that have not been 
developed yet, so we cannot describe them to you now. We will only use your stored samples to learn 
more about how the immune system responds to Ebola and how vaccines can prevent Ebola infection. 
Your Samples Used for Future Research Will Be Shipped to the USA 
Your samples will be stored in a secure central storage site (not in the clinic) in the USA. The samples 
will not be labeled with your name, only with your Study Identification (SID) number. There is no time 
limit on how long your samples will be stored.  
Your Privacy Will Be Protected 
We will protect your privacy with any future research testing of your samples, just like we do with all 
research information from you during the main study. The samples will not be labeled with your name. 
Instead, they will have your study code. After this study ends, when the samples are requested for future 
research, the study code stays with them, or in some cases, it is removed before the samples are sent to 
be used, if this information is not necessary for the study.  
An Institutional Review Board/Independent Ethics Committee Will Review Any Future Research 
on Your Samples 
An IRB/Independent Ethics Committee, which is responsible for overseeing the safety, welfare and 
rights of research participants, must review and approve each research study that intends to use your 
samples in future studies.  
There Will Be No Benefit to You If You Allow Us to Store Your Samples For Future Research 
The researchers will not contact you or your health care provider with results from future studies or 
future genetic tests that use your samples. This is because the use of the samples is for research and the 
tests have not been approved for use in making health care decisions. 
Your samples may contribute to a new invention or discovery. There is no plan for you to share any 
money or other benefits resulting from this invention or discovery.  
There Are Few Risks Related to Storing Your Samples 
When tests are done on the stored samples there is a small but possible risk to your privacy. It is possible 
that if others found out information about you that is learned from tests (such as information about your 
genes) it could cause you problems with your family (e.g., having a family member learn about a disease 
that may be passed on in families or learning who is the true parent of a child) or problems getting a job 
or insurance. The risk of this happening is extremely low, because your results will not be a part of your 
medical record and will not be given to the clinic. Also, it is possible that your SID could be removed 
from the samples. If your SID number is removed from any samples, we will not be able to link that 
sample to you. 

RV 508/WRAIR #2439 
 
Version 1.5 
Future Use ICF 
Page 3 of 3 
03 March 2020 
You Can Agree Now to Let Us Use Your Samples For Future Testing and Still Change Your Mind 
Later 
If you agree now, but decide later that you do not want us to use your samples for future research, please 
tell us. We will ask the storage facility to destroy any remaining samples that still have your SID on 
them so that they cannot be used for future research. 
For More Information: 
If you have questions about the use of your samples for future research, contact Dr. Betty Mwesigwa on 
 or toll free on 
 
If you have a problem that you think may be related to the use of your samples for future research, or if 
you want to withdraw your consent, contact Immaculate Nakabuye on 
 
If you have questions about your rights as a research participant, or problems or concerns about how you 
are being treated in this study, you may contact 
the Research and Ethics 
Committee, Makerere University School of Public Health, Mulago Hospital Complex or o
Once you have read this form and have had all of your questions satisfactorily answered, please initial 
and check the box next to your choice of whether or not you consent to have your blood samples stored 
for future testing, and then sign in the space provided below. 
_____ 
initials 
 
I allow you to store and use my samples for future testing which may include genetic 
testing. 
_____ 
initials 
 
I do not allow you to store and use my samples for future testing. 
 
 
_________________________________________________ 
 ___________ 
SIGNATURE OR MARK OF PARTICIPANT 
DATE 
 
 
_______________________________________________________ 
PRINT NAME OF PARTICIPANT 
 
 
_________________________________________________ 
 ___________ 
SIGNATURE OF PERSON ADMINISTERING CONSENT 
DATE 
 
 
_______________________________________________________ 
PRINT NAME OF PERSON ADMINISTERING CONSENT 

RV508/WRAIR#2439
Version1.5

03March2020
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Page79of145
APPENDIX2C:INFORMEDCONSENTFORGENETICTESTING



RV 508/WRAIR #2439 
 
Version 1.5 
Genetic ICF 
Page 1 of 3 
03 March 2020 
INFORMED CONSENT FOR GENETIC TESTING 
 
Study Title:  RV 508, “A Phase I Open-Label, Dose-Escalation Clinical Trial to Evaluate the Safety, 
Tolerability and Immunogenicity of Two Doses of an Ebola Sudan Chimpanzee 
Adenovirus Vector Vaccine, VRC-EBOADC086-00-VP (cAd3-EBO S), in Healthy 
Adults” 
Sponsor: National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases 
(NIAID) Vaccine Research Center (VRC) 
Funding Agencies: NIH, the U.S. Military HIV Research Program (MHRP) and the U.S. Department of 
Defense (DoD) 
Study Product Provided by: NIH/NIAID/VRC 
Study Conducted by: Makerere University Walter Reed Project (MUWRP) 
Principal Investigator: Betty Mwesigwa, MBChB, MSc Clinical Trials 
 
As we told you in the main informed consent form for this study and in the consent form for storage of 
samples for future use, we will do some testing of your blood. Some of the testing that we will do will 
be genetic testing. This consent form tells you everything we know now about genetic testing using your 
blood samples.  
You can decide whether or not to let us use your blood for genetic tests. Your decision does not affect 
your participation in the study or any care you receive at this clinic. If you decide to allow us to use your 
blood samples for genetic tests, we will ask you to sign this form. You will get a copy of the form to 
keep. 
Your Blood Sample Is a Potential Source of Genetic Information 
Researchers are able to measure how the immune system responds by looking at blood. We will try to 
understand why Ebola and other diseases affected by Ebola progress differently in some people and why 
some people are more likely to become infected than others. We know that sometimes genes, passed 
down from your parents, can be important to a person’s immune response to Ebola. Because of this, we 
would like to do genetic testing on your blood samples. We will only perform genetic testing to learn 
more about how the immune system responds to Ebola and to other diseases affected by Ebola. 
HLA and Genetic Testing: Some of the blood drawn from you, as part of this study will be used for a 
test called HLA type. HLA stands for ‘Human Leukocyte Antigen’, a group of proteins present on the 
surface of all cells on the human body and help the body’s immune system respond to foreign, harmful 
substances. For research, HLA testing is used to try to identify factors associated with response to a 
vaccine, progression of a disease or related conditions. Determining HLA type is necessary to be able to 
perform certain research studies. 
We will not notify you of the results of any genetic test. The genetic research tests we plan to conduct 
are not currently used in medical practice and have not been approved for use in making health care 
decisions.  

RV 508/WRAIR #2439 
 
Version 1.5 
Genetic ICF 
Page 2 of 3 
03 March 2020 
Your Samples Used For Genetic Testing Will Be Shipped to the USA 
In order to complete the genetic testing on your blood samples, they will be shipped and stored in the 
United States. There is no time limit on how long your samples will be stored.  
Your Privacy Will Be Protected 
We will protect your privacy with any genetic testing of your blood samples, just like we do with all 
research information from you during the study. The blood samples will not be labeled with your name. 
Instead, they will have your study identification (SID) number only. If your samples are sent outside 
Uganda, the SID number stays with them. Your genetic test results will only be connected to you by the 
SID number, known only to the study team, and not by your name or other personal information. 
There Will Be No Benefit to You If You Allow Us to Use Your Samples For Genetic Testing 
The researchers will not contact you or your health care provider with results from the genetic testing 
using your blood. This is because the use of the samples is for research and the tests have not been 
approved for use in making health care decisions. 
Your samples may contribute to a new invention or discovery. There is no plan for you to share any 
money or other benefits resulting from this invention or discovery. 
There Are Few Risks Related to Genetic Testing of Your Samples 
Risk of genetic tests and HLA testing: The greatest risk associated with genetic testing is to your 
privacy. Genetic test results can be used to provide information about how susceptible you are to certain 
diseases. Used inappropriately, this information could be discriminatory (for example, by insurance 
companies). HLA typing can also be used to determine who the true parent of a child is (if compared to 
the child’s HLA type). However, the risk of this happening is extremely low, because your results will 
not be part of your medical records and will not be provided to the clinic.  
The blood samples that you provide will only be used to provide study investigators information about 
your immune system. The results will be coded to protect your identity. Your HLA (and other genetic 
tests) can only be connected to you by the coded study number and not by your name or other personal 
information. Neither you nor your doctor will be given the results of the tests.  
For More Information: 
If you have questions about the use of your samples for genetic testing, contact Dr. Betty Mwesigwa on 
or toll free on 
If you have a problem that you think may be related to the use of your samples for genetic testing, or if 
you want to withdraw your consent, contact Immaculate Nakabuye on 
 
If you have questions about your rights as a research participant, or problems or concerns about how you 
are being treated in this study, you may contact 
the Research and Ethics 
Committee, Makerere University School of Public Health, Mulago Hospital Complex or 

RV 508/WRAIR #2439 
 
Version 1.5 
Genetic ICF 
Page 3 of 3 
03 March 2020 
Once you have read this form and have had all your questions satisfactorily answered, please initial and 
check the box next to your choice of whether or not you consent to have your blood samples used for 
genetic testing, and then sign in the space provided below. 
_____ 
 
I allow you to use my samples for genetic testing. 
initials 
_____ 
 
I do not allow you to do genetic testing on my samples. 
initials 
 
 
_________________________________________________ 
 ___________ 
SIGNATURE OR MARK OF PARTICIPANT 
DATE 
 
 
_______________________________________________________ 
PRINT NAME OF PARTICIPANT 
 
 
_________________________________________________ 
 ___________ 
SIGNATURE OF PERSON ADMINISTERING CONSENT 
DATE 
 
 
_______________________________________________________ 
PRINT NAME OF PERSON ADMINISTERING CONSENT 

RV508/WRAIR#2439
Version1.5

03March2020

Page83of145
APPENDIX2D:WITHDRAWALOFCONSENTFORSAMPLESTORAGE



RV 508/WRAIR #2439 
 
Version 1.5 
Withdraw Samples Form 
Page 1 of 1 
03 March 2020 
WITHDRAWAL OF CONSENT FOR SAMPLE STORAGE 
 
Study Title:  RV 508, “A Phase I Open-Label, Dose-Escalation Clinical Trial to Evaluate the Safety, 
Tolerability and Immunogenicity of Two Doses of an Ebola Sudan Chimpanzee 
Adenovirus Vector Vaccine, VRC-EBOADC086-00-VP (cAd3-EBO S), in Healthy 
Adults” 
Sponsor: National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases 
(NIAID) Vaccine Research Center (VRC) 
Funding Agencies: NIH, the U.S. Military HIV Research Program (MHRP) and the U.S. Department of 
Defense (DoD) 
Study Product Provided by: NIH/NIAID/VRC 
Study Conducted by: Makerere University Walter Reed Project (MUWRP) 
Principal Investigator: Betty Mwesigwa, MBChB, MSc Clinical Trials 
 
Volunteer Statement of withdraw of consent to have samples stored for future testing: 
I ___________________________________ withdraw my consent to have my samples stored for future 
use. I do not want to donate blood samples for storage and future use. However, I would still like to 
continue taking part in the main study. It has been explained to me that when I sign at the bottom of this 
form, my samples will be used for all the tests specified for this present study, but no blood will be 
stored for future use. 
It has been explained to me that withdrawing my consent to have my samples stored for future use will 
not make any difference to the care I am receiving now or in the future, or to any benefits that I am 
entitled to. 
I have been given a chance to ask all the questions that I have about withdrawing my consent to have my 
samples stored. All of my questions were answered to my satisfaction. I was offered a signed copy of 
this consent. 
 
_________________________________________________ 
 ___________ 
SIGNATURE OR MARK OF PARTICIPANT 
DATE 
 
 
_______________________________________________________ 
PRINT NAME OF PARTICIPANT 
 
 
_________________________________________________ 
 ___________ 
SIGNATURE OF PERSON ADMINISTERING CONSENT 
DATE 
 
 
_______________________________________________________ 
PRINT NAME OF PERSON ADMINISTERING CONSENT 

RV508/WRAIR#2439
Version1.5

03March2020

Page85of145
APPENDIX3:VOLUNTEEREVENTSCHEDULE



RV 508/WRAIR #2439 
Page 1 of 2 
Version 1.5 
Volunteer Event Schedule 
 
03 March 2020 
Volunteer Event Schedule 
 
Study Day 
Timeline 
Visit ID 
Procedures 
Compensation 
Scheduled 
Date 
-56 to 0 days 
pre-vaccination 
Visit # 1 
Screening Visit 
(2 to 3 hours) 
• 
Informed Consent Process 
• 
Assessment of Understanding 
• 
Physical Exam, Weight, Height, Vitals 
• 
Complete Medical History 
• 
HIV Counseling and test 
• 
Syphilis test 
• 
Blood draw 
• 
Urine collection 
• 
Pregnancy test, if female 
 
UG SHS 50,000 
 
Week 0 
Day 0  
Visit # 2 
Enrollment and 
Vaccination 
(2 to 3 hours) 
• 
Physical Exam (as required) 
• 
Updating medical history and assessments 
• 
Vaccination 
• 
Discuss Diary Card (to be completed in 
the evening) 
• 
Blood draw 
• 
Females: Pregnancy test & counseling 
 
UG SHS 50,000 
 
Week 1 
1 day post-
vaccination 
(+ 1 day) 
Visit # 2A 
(5 minutes) 
• 
Phone contact with clinic, clinic visit if 
necessary 
 
UG SHS 20,000 
if clinic visit is 
requested by 
study doctor 
 
Week 1 
3 days post-
vaccination 
(+ 2 days) 
 
Visit # 2B 
(30 minutes) 
• 
Physical Exam (as required) 
• 
Updating medical history and assessments 
• 
Blood draw 
• 
Diary Card review 
 
UG SHS 50,000 
 
Week 1 
7 days post-
vaccination 
(+ 3 days) 
 
Visit # 2C 
(30 minutes) 
• 
Physical Exam (as required) 
• 
Updating medical history and assessments 
• 
Blood draw 
• 
Diary Card review 
 
UG SHS 50,000 
 

RV 508/WRAIR #2439 
Page 2 of 2 
Version 1.5 
Volunteer Event Schedule 
 
03 March 2020 
Study Day 
Timeline 
Visit ID 
Procedures 
Compensation 
Scheduled 
Date 
Week 2 
14 days post-
vaccination  
(± 3 days) 
 
Visit # 2D 
(30 minutes) 
• 
Physical Exam (as required) 
• 
Updating medical history and assessments 
• 
Blood draw 
• 
Females: pregnancy prevention 
counseling 
 
UG SHS 50,000 
 
Week 4 
(± 7 days) 
 
Visit # 3 
(30 minutes) 
• 
Physical Exam (as required) 
• 
Updating medical history and assessments 
• 
Blood draw 
• 
Urine collection 
• 
Females: Pregnancy test & counseling 
 
UG SHS 50,000 
 
Week 8 
(± 7 days) 
 
Visit # 4 
(30 minutes) 
• 
Physical Exam (as required) 
• 
Updating medical history and assessments 
• 
Blood draw 
• 
Females: pregnancy prevention 
counseling 
 
UG SHS 50,000 
 
Week 16 
(± 14 days) 
 
Visit # 5 
(30 minutes) 
• 
Physical Exam (as required) 
• 
Updating medical history and assessments 
• 
Blood draw 
• 
Females: pregnancy prevention 
counseling 
 
UG SHS 50,000 
 
Week 24  
(± 14 days) 
 
Visit # 6 
(30 minutes) 
• 
Physical Exam (as required) 
• 
Updating medical history and assessments 
• 
Blood draw 
• 
Urine collection 
• 
Pregnancy test, if female 
 
UG SHS 50,000 
 
Week 48 
(± 14 days) 
 
Visit # 7 
(30 minutes) 
• 
Physical Exam (as required) 
• 
Updating medical history and assessments 
• 
Blood draw 
 
UG SHS 50,000 
 
 

RV508/WRAIR#2439
Version1.5

03March2020
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Page88of145
APPENDIX4:ASSESSMENTOFUNDERSTANDING



RV 508/WRAIR #2439 
 
Version 1.5 
Assessment of Understanding 
 
03 March 2020 
ASSESSMENT OF UNDERSTANDING 
PleasereadeachquestionandanswerwhetherthestatementisTrueorFalse.

True False
1.
Themainpurposeofthestudyistoseeiftheexperimentalvaccineis
safe.
True

False

2.
ThevaccineinthisstudywilldefinitelyprotectmeagainstEbola.
True False
3.
IwillbeabletochoosewhichdoseofthevaccineIreceive.
True

False

4.
Therewillbenodirectbenefittomeforparticipatinginthestudy.
True

False

5.
Imayleavethestudyatanytime.
True

False

6.
Participationinthestudywilllastforapproximately48weeks(11
months).
True

False

7.
IfIgivepermission,samplesofmybloodwillbecollectedandstored
inaresearchlaboratoryandmaybeusedforfutureresearchstudies.
True

False

8.
Womenparticipatinginthestudymustuseeffectivebirthcontrol21
dayspriortoreceivingthevaccinethrough24weeks(6months)after
studyvaccination.
True

False

9.
ThereisapossibilitythatIcanbecomeinfectedwithEbolafromthe
studyvaccine.
True False
10.
Iwillbeaskedtokeepadetaileddiaryofpossiblesideeffectsfor
sevendaysaftervaccination.


RV 508/WRAIR #2439 
 
Version 1.5 
Assessment of Understanding Answer Key 
 
03 March 2020 
ASSESSMENT OF UNDERSTANDING ANSWER KEY 
PleasereadeachquestionandanswerwhetherthestatementisTrueorFalse.

True False

1.
Themainpurposeofthestudyistoseeiftheexperimentalvaccineis
safe.
True

False

2.
ThevaccineinthisstudywilldefinitelyprotectmeagainstEbola.
True False

3.
IwillbeabletochoosewhichdoseofthevaccineIreceive.
True

False

4.
Therewillbenodirectbenefittomeforparticipatinginthestudy.
True

False

5.
Imayleavethestudyatanytime.
True

False

6.
Participationinthestudywilllastforapproximately48weeks(11
months).
True

False

7.
IfIgivepermission,samplesofmybloodwillbecollectedandstored
inaresearchlaboratoryandmaybeusedforfutureresearchstudies.
True

False

8.
Womenparticipatinginthestudymustuseeffectivebirthcontrol21
dayspriortoreceivingthevaccinethrough24weeks(6months)after
studyvaccination.
True

False

9.
ThereisapossibilitythatIcanbecomeinfectedwithEbolafromthe
studyvaccine.
True False

10.
Iwillbeaskedtokeepadetaileddiaryofpossiblesideeffectsfor
sevendaysaftervaccination.


RV508/WRAIR#2439
Version1.5

03March2020

Page91of145
APPENDIX5:BRIEFINGSLIDES




A Presentation By:
Join Hands with Makerere University-Walter Reed 
Project
in Consultation with
The National Institutes of Health, Vaccine Research 
Center and the
United States Military HIV Research Program to 
Develop an Ebola Vaccine
	


Basic Information:
Study Title: “A Phase 1 Open-Label, Dose-Escalation 
Clinical Trial to Evaluate the Safety, Tolerability and 
Immunogenicity of Two Doses of an Ebola Sudan 
Chimpanzee Adenovirus Vector Vaccine, VRC-
EBOADC086-00-VP (cAd3-EBO S), in Healthy Adults”
Study Location: Makerere University-Walter Reed Project 
(MUWRP)
Principal Investigator: Betty Mwesigwa, MBChB, MSc in 
Clinical Trials

	



Purpose of this Presentation
To provide you with detailed information about:
 The Ebola vaccine study
 Risks and benefits associated with the study
 Who may and may not participate
 The study visits
 The study procedures
 Your rights as a participant

	


The Objectives of this Study
 The study will evaluate the following for this 
vaccine:
 Safety (Is it safe in human beings?)
 Tolerability (Can you easily endure the side 
effects?)
 Immune responses
 Immune responses are the ways your body 
recognizes and defends itself against bacteria, 
viruses, or anything that appears harmful to the 
body.

	



WhatVaccine is Being Tested?
 The investigational Ebola vaccine being tested in 
this study is called VRC-EBOADC086-00-VP and 
is referred to as “cAd3-EBO S”
 This experimental vaccine was developed by the 
US National Institute of Health (NIH) and the 
Vaccine Research Center (VRC).

	


Potential Risks and Discomforts
General Injection Risks
You may get some side effects after vaccination:
 Stinging, itching, arm discomfort, injection site 
pain, soreness, tenderness and/redness, hardness, 
bruising and swelling at the site of injection. There 
is a very small chance of infection.
 These reactions may occur with all types of injections. 

	



Potential Risks and Discomforts
General Vaccination Risks
 Also possible that you could get a fever, chills, rash, general itching, 
aches and pains, muscle pain, joint pain, vomiting, nausea, headache, 
dizziness, fatigue (feeling tired), and malaise (feeling unwell)
 Most side effects usually do not last very long (48-72 hrs) and do 
not require treatment. 
 You may take medications to help with pain control and inflammation 
after the injection, but please report their use to the study staff
 It is rare, but you could have an allergic reaction to a vaccine, 
including a rash, hives, or difficulty breathing
 Some allergic reactions can be life-threatening therefore, 
you will need to stay at the clinic, where the staff will watch you 
for 30 to 60 minutes after the injection and you may need to stay 
longer if the study doctor thinks it is best for you

	


Potential Risks and Discomforts
Experimental Vaccine Risks
 There may be unknown risks with the use of the 
vaccine 
 The most common complaints in the first few days 
after receiving similar vaccines include sore arm, 
headache, muscle aches, and feeling tired.  A few 
people had a fever within a day after vaccination
 Receiving the vaccine does NOT mean you are 
protected against Ebola and you SHOULD 
continue to follow all recommended precautions 
against Ebola

	



Other Risks, Hazards and Discomforts
 Drawing blood may cause pain and bruising, light-
headedness or fainting and rarely, infection at the 
site where blood is drawn
 You may not donate blood while participating in 
this study or for one year after receiving the 
experimental vaccine
 An accidental release of genetic testing results 
could provide information that may be used against 
you, however to minimize this risk the results will 
only be labeled with a code, not your name or 
other identifying information

Potential Risks and Discomforts
	


Unknown Risks to Pregnancy and Fetus
 The risk to pregnant women, fetuses, and infants 
is unknown, therefore women who are pregnant, 
breast-feeding, or plan to become pregnant within 
24 weeks (6 months) of receiving the vaccine 
cannot participate in the study
 Women who are capable of becoming pregnant 
will undergo pregnancy testing during the study 
and must agree to use adequate methods of birth 
control beginning 21 days prior to receiving the 
study vaccine until 24 weeks (6 months) after 
receiving the study vaccine

Potential Risks and Discomforts
	



Unknown Risks to Pregnancy and Fetus (continued)
 Adequate methods of birth control include:
 Condoms (male or female), with or without a 
spermicide
 Diaphragm or cervical cap with spermicide
 Intrauterine device
 All prescription methods (such as contraceptive pills, 
injections, patches and others)
 A male partner who has previously undergone a 
vasectomy
 Should you become pregnant while enrolled in 
this study, you will not receive the vaccination
 You will be followed up for your and your baby’s safety

Potential Risks and Discomforts
	


Safeguards
 You will be closely monitored by the study team.
 Blood tests will be conducted regularly 
throughout the study in order to detect any 
unforeseen or adverse reactions.
 You will be asked to return to the clinic for lab 
abnormalities or other concerns.

	



Benefits
There is no direct benefit to you by being in this 
study, (we do not know if the study vaccine will work 
against Ebola infection) however:
 You may learn more about your health,
 You and others may benefit in the future from the 
information that will be learned from the study. The 
results of this study could play a role in future vaccine 
development.

	


Who Can Participate in the Study?

You can participate if you:
 Are a man or woman between the ages of 18 and 50 years old
 Are available and willing to participate for the duration of the study 
visits and follow-up (48 weeks)
 Are healthy in the investigator’s clinical judgment (lab test, exam, etc)
 Are able to provide proof of identity to the statisfaction of the 
investigator
 Are able and willing to provide fingerprints and have photographs taken 
including injection site photographs
 Are willing and able to provide informed consent
 Have reliable means to be contacted (for example a cell phone or 
through home visit)
 Are HIV negative
 Are not pregnant
 (If female and able to become pregnant) agree to use contraception 
from 21 days before vaccination to 24 weeks after vaccination
	



Who Cannot Participate in the Study?
You cannot participate if you:
 Have received any other Ebola or Marburg vaccine, or cAd3-based 
vaccine in the past
 Have a bleeding problem or disorder
 Have an active syphilis infection
 Have an autoimmune disease or immunodeficiency
 Have diabetes (type I or II)
 Have thyroid disease that is not well controlled
 Have high blood pressure or asthma that is not well controlled
 Have cancer that is active, currently being treated, or not surgically cured
 Have a history of seizures
 Have a history of serious allergic reaction (anaphylaxis) to any vaccines or 
allergic reaction to drugs like gentamycin, neomycin or streptomycin

	


You cannot participate if you (continued):
 Are pregnant, breastfeeding, or plan to become pregnant for 24 weeks 
after receiving the vaccine
 Have a history of clinically significant condition(s) that might interfere 
with participation or that may impair your ability to provide informed 
consent
 Have received any of the following:
 Drugs that may modify your immune system within 14 days prior 
to enrollment e.g. Prednisolone or dexamethasone
 Blood products within 112 days (16 weeks) prior to enrollment
 Any “live-attenuated” vaccine (e.g. oral polio, yellow fever, measles, 
etc.) within 28 days prior to enrollment in the present study or any 
other vaccine within 14 days prior to enrollment
 Experimental research drugs or vaccines within 28 days prior to 
enrollment in the present study
 Drugs for treating or preventing Tuberculosis

Who Cannot Participate in the Study?
	




 
	


Overall Study Design
 Phase I open-label, dose-escalation clinical trial
 Sponsored by the US NIH/NIAID/VRC in collaboration 
with the MHRP
 A total of 40 volunteers will be enrolled from Kampala, 
Uganda
 20 volunteers will receive a low dose of vaccine
 20 volunteers will receive a higher dose of vaccine
 Interim safety reviews will be conducted throughout the 
study to ensure the safety of participants
 Once enrollment is completed for Group 1 and no safety 
issues are identified, enrollment into Group 2 will begin

Group
Participants
Dose
1
20
cAd3-EBO S at 1 x 1010 PU IM
2
20
cAd3-EBO S at 1 x 1011 PU IM
	



ScreeningVisit
 You will review and voluntarily sign a consent form
 Your understanding of the study will be 
determined by you completing and passing an 
Assessment of Understanding.
 The study doctor will take your medical history 
and perform a physical exam 
 Blood and urine samples will be taken to test your 
general health including testing for HIV and urine 
for pregnancy.

Study Visit Procedures
	


Study Visit Procedures
 If you are healthy and do not have any condition 
which prevents you from taking part in the study, 
based upon the screening visit, you will be asked to 
return to the clinic for a review of your laboratory 
and HIV results. 
 If the results of your screening medical evaluation identify 
a problem which prevents you from participating in the 
study, you will be referred to a health care provider, if 
needed.
 If you are eligible and still willing to participate, you 
will receive the vaccination at the second visit

	



 At every visit you will have blood drawn from a 
vein in your arm, ranging from a volume of about 
25 mL (about 5 teaspoons) to about 92 mL (about 
6 tablespoons) 
 Over the whole study, the amount of blood that 
you will give is less than 700 mL (about 1.5 
tumpeco mugs)
 You will not have more than 450 mL of blood 
drawn over any 3-month period during the study

Study Visit Procedures
	



Vaccination Day
 If you are eligible and willing to participate, you will 
receive the vaccination at visit 2
 The vaccination will be given (by needle & syringe) into 
the upper arm as a  mL dose of the experimental Ebola 
vaccine
 On the vaccination day, you will be in the clinic for about 
2 – 3 hours and will be required to remain at the clinic 
for 30 to 60 minutes after vaccination (or longer if the 
study investigator thinks it’s necessary)
 Should you develop any symptoms that are of concern to 
you or to the study team, you will be asked to return to 
the clinic
Study Visit Procedures
	



After the Vaccination
 You will be asked to complete a diary card at home in the 
evening on the day of vaccination and about the same time 
for the next seven (7) days
 You will return to the clinic 3 days after the vaccination, 
but the study team will contact you  day after the 
vaccination to see how you feel

Study Visit Procedures
	


Follow-Up Visits
 You will have 8 scheduled clinic visits after vaccination
 During each scheduled visit, the doctor will perform a brief 
medical history and physical exam, and remind you about 
contraception.
 Blood will be collected for routine laboratory safety studies 
and to identify the body’s responses to the vaccine
 Remember: You can report any symptoms, problems or 
concerns you have to the study team at any time!

Study Visit Procedures
	




!"#$%% 
"&'
	


Confidentiality
 All volunteers will be assigned study numbers 
that are known only to the investigators
 All research samples, lab results and study 
records will be identified by a study number and 
not by your name. 
 All documents which bear your name will be 
securely locked in a cabinet, in a locked room 
with restricted access.
 Your study documents may be accessed by 
representatives of IRBs, the Sponsor and 
regulatory bodies e.g. NDA, UNCST

	



Ending Participation
Your participation may end for the following reasons:
 Decision by the investigator:
 For safety reasons
 Repeated failure to comply with instructions
 Decision by the sponsor or investigator to stop or 
cancel the study
 Decision by local regulatory authorities (NDA/ 
UNCST) and IRB (MUSPH) to stop or cancel the 
study
 You decide to withdrawal your consent

	


Compensation
 For taking part in this study you will receive 
50,000 Ushs after each scheduled visit to 
compensate you for your time, transportation and 
inconveniences 
 20,000 Ushs for unscheduled visits to address 
safety concerns. Compensation for unscheduled 
visits will be at the investigator’s discretion

	



Medical Care for Injury or Illness
 Should you be injured as a direct result of taking 
part in this research project, you will be provided 
medical care, at no cost to you until complete cure 
or stabilization of the research related injury
 You will not receive any compensation for injury 
and will not be asked to waive your legal rights
 You should discuss this issue thoroughly with the 
principal investigator before you enroll in this 
study

	


Final Reminders
 If you are pregnant or plan to become pregnant 
during the study, you will not be able to 
participate
 Your participation in the trial is completely 
voluntary and you may withdraw at any time for 
any reason 
 Your decision not to participate in the study, or a 
decision on your part to withdraw from the study will 
have no effect whatsoever on your healthcare and 
employment status
 You may refuse to participate or you may withdraw from 
the study at any time without penalty or prejudice
 Close communication with study staff is key for 
your safety

	



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RV508/WRAIR#2439
Version1.5

03March2020

Page109of145
APPENDIX6:GRADINGSEVERITYOFADVERSEEVENTS
FDA Guidance for Industry (September 2007): “Toxicity Grading Scale for Healthy Adult and
AdolescentVolunteersEnrolledinPreventiveVaccineClinicalTrials”
ModificationtotheFDAAEGradingTable
IndividualsofAfricandescenthavelowerneutrophilcountsthanindividualsofotherethnicities.Astudy
evaluating the reasons for ineligibility in phase I and II HIV vaccine trials in East Africafound that
approximatelyonethirdofsubjectswereexcludedbecauseofneutropenia.The phaseIand IIstudies
used normal ranges from U.S. populations, not from African populations. If neutrophil ranges from
East/South Africa populations were used instead, over one half of the subjects excluded because of
hematologicabnormalitiescouldhavebeenincluded(ref.).Sincethisstudywillbeconductedinpartin
EastAfrica,wewillusethenormalneutrophilrangefromEast/SouthAfrica(1.0 –5.3x103cells/ul,
(ref.)forsubjectsinUgandaorothersubjectsofAfricandescent.Gradesforabsoluteneutrophilcountin
thesesubjectswillbeasfollows:
Grade1
Grade2
Grade3
Grade4
Absolute
NeutrophilCount
(cells/ul)
750– 999
500– 749
250– 499
< 250
Forothersubjects,theusualFDAAEgradingscalewillbeusedasfollows:
Grade1
Grade2
Grade3
Grade4
Absolute
NeutrophilCount
(cells/ul)
–1,500– 2,000
1,000-1,499
500- 999
< 500

AssessmentofCausalityRelationshipofanAdverseEvent(AE)toStudyVaccine:

TherelationshipbetweenanAEandthevaccinewillbeassessedbytheinvestigatoronthebasisofhisor
herclinicaljudgmentandthedefinitionsbelow.
·
DefinitelyRelated.TheAEandadministrationofstudyagentarerelatedintime,andadirect
associationcanbedemonstrated.
·
ProbablyRelated.TheAEandadministrationofstudyagentarereasonablyrelatedintime,
andtheAEismorelikelyexplainedbystudyagentthanothercauses.
·
PossiblyRelated.TheAEandadministrationofstudyagentarereasonablyrelatedintime,
buttheAEcanbeexplainedequallywellbycausesotherthanstudyagent.
·
NotRelated.ThereisnotareasonablepossibilitythattheAEisrelatedtothestudyagent.
ForpurposesofpreparingdatareportsinwhichAEattributionsarelimitedto“Related”or“Not
Related”,inthisprotocol,the“Definitely,ProbablyandPossibly”attributionswillbemappedtothe
“Related”category.Thedefinitionsthatapplywhenthesetwocategoriesaloneareusedareasfollows:
·
Related–ThereisareasonablepossibilitythattheAEmayberelatedtothestudyagent.
·
NotRelated–ThereisnotareasonablepossibilitythattheAEisrelatedtothestudyagent.
GradingtheSeverityofAdverseEvents:
TheFDAGuidanceforIndustry(September2007):“ToxicityGradingScaleforHealthyAdultand
AdolescentVolunteersEnrolledinPreventiveVaccineClinicalTrials”isthebasisfortheseverity
gradingofadverseeventsinthisprotocol.Severalmodificationsweremadetothetableasfollows:

RV508/WRAIR#2439
Version1.5

03March2020

Page110of145
·
“Emergencyroomvisit”isnotautomaticallyconsideredalife-threateningevent;thesewordshave
beenremovedfromany“grade4’definitionwheretheyappearinthetablecopiedfromtheguidance
document.
·
Anylaboratoryvalueshownasa“graded”valueinthetablethatiswithintheinstitutionalnormal
rangewillnotbeseveritygradedorrecordedasanadverseevent.
·
Severitygradingforhemoglobindecreaseonthebasisofthemagnitudeofdecreasefrombaselineis
notapplicableatthegrade1level;onlyabsolutehemoglobinwillbeusedtodefinegrade1.Increases
inhemoglobinareAEsonlyforvaluesabovetheupperlimitofnormalandaregradedbythe
systemicillnessclinicalcriteria.
·
SeveritygradingdefinitionforGrade4localreactiontoinjectableproduct(Erythema/Rednessand
Induration/Swelling)includesaddedtext“requiringmedicalattention”.
·
1XULNwasremovedfromthedefinitionforPTincrease.
·
Severitygradingdefinitionforhypotensionincludesaddedclarificationssuchthatanasymptomatic
lowbloodpressurereadingisnotanadverseevent.
·
SeveritygradingforneutropeniaisprovidedforsubjectsofAfricandescentbasedonnormalranges
observed.

Whennototherwisespecifiedinthetable,thefollowingguidancewillbeusedtoassignaseveritygrade:
Grade1(Mild):Noeffectonactivitiesofdailyliving
Grade2(Moderate):Someinterferencewithactivitynotrequiringmedicalintervention
Grade3(Severe):Preventsdailyactivityandrequiresmedicalintervention
Grade4(PotentiallyLife-threatening):Hospitalization;immediatemedicalinterventionortherapy
requiredtopreventdeath.
Grade5(Death):DeathisassignedaGrade5severity.
Onlythesingleadverseeventthatisassessedastheprimarycauseofdeathshouldbeassigned“grade5”
severity.

RV508/WRAIR#2439
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03March2020
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Page111of145
ToxicityGradingScaleforHealthyAdultandAdolescentVolunteersEnrolledin
PreventiveVaccineClinicalTrials
ModifiedfromFDAGuidance-September2007

A. TablesforClinicalAbnormalities
LocalReactionto
InjectableProduct
Mild
(Grade1)
Moderate
(Grade2)
Severe
(Grade3)
PotentiallyLife
Threatening
(Grade4)
Pain
Doesnotinterfere
withactivity
Repeateduseofnon-
narcoticpainreliever
>24hoursor
interfereswith
activity
Anyuseofnarcotic
painrelieveror
preventsdaily
activity
Hospitalization
Tenderness
Milddiscomfortto
touch
Discomfortwith
movement
Significant
discomfortatrest
Hospitalization
1Erythema/Redness
2.5– 5cm
5.1– 10cm
>10cm
Necrosisor
exfoliativedermatitis
requiringmedical
attention
2Induration/Swelling
2.5– 5cmanddoes
notinterfere
withactivity
5.1– 10cmor
interfereswith
activity
>10cmor
preventsdaily
activity
Necrosisrequiring
medicalattention
3VitalSigns
Mild
(Grade1)
Moderate
(Grade2)
Severe
(Grade3)
PotentiallyLife
Threatening
(Grade4)
4Fever(°C)
(°F)
38.0– 38.4
100.4– 101.1
38.5– 38.9
101.2– 102.0
39.0– 40
102.1– 104
> 40
>104
Tachycardia- beatsper
minute
101– 115
116– 130
>130
Hospitalizationfor
arrhythmia
5Bradycardia- beatsper
Minute
50– 54
45– 49
<45
Hospitalizationfor
arrhythmia
Hypertension(systolic)-
mmHg
141– 150
151– 155
>155
Hospitalizationfor
malignant
hypertension
Hypertension(diastolic)-
mmHg
91– 95
96– 100
>100
Hospitalizationfor
malignant
hypertension
Hypotension(systolic)–
mmHg
85– 89and
symptomatic
80– 84and
symptomaticand
requiringoralfluids
<80and
symptomaticand
requiringIVfluids
Hospitalizationfor
hypotensiveshock
6RespiratoryRate– breaths
perminute
17– 20
21– 25
>25
Intubation
1. Inadditiontogradingthemeasuredlocalreactionatthegreatestsinglediameter,themeasurementshouldberecordedas
acontinuousvariable.
2. Induration/Swellingshouldbeevaluatedandgradedusingthefunctionalscaleaswellastheactualmeasurement.
3. Subjectshouldbeatrestforallvitalsignmeasurements.
4. Oraltemperature;norecenthotorcoldbeveragesorsmoking.
5. Whenrestingheartrateisbetween60–100beatsperminute,useclinicaljudgmentwhencharacterizingbradycardia
amongsomehealthysubjectpopulations,forexample,conditionedathletes.
6. Whenrestingrespiratoryrateisgreaterthanorequalto17,useclinicaljudgmentwhencharacterizingtachypneaamong
healthysubjectpopulationsandconsiderbaselinerespiratoryrate,relevantlocalnormalvaluesandotherinfluences(e.g.
elevation).


RV508/WRAIR#2439
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
03March2020
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Page112of145
Systemic(General)
Mild
(Grade1)
Moderate
(Grade2)
Severe
(Grade3)
PotentiallyLife
Threatening
(Grade4)
Nausea/vomiting
Nointerference
withactivityor1–2
episodes/24hours
Someinterference
withactivityor>2
episodes/24hours
Preventsdaily
activity,requires
outpatientIV
hydration
Hospitalizationfor
hypotensiveshock
Diarrhea
2– 3loosestoolsor
<400gms/24hours
4– 5stoolsor
400–800gms/24
hours
6ormorewatery
stoolsor
>800gms/24hours
orrequires
outpatientIV
hydration
Hospitalization
Headache
Nointerferencewith
activity
Repeateduseofnon-
narcoticpain
reliever>24hoursor
someinterference
withactivity
Significant;any
useofnarcotic
painrelieveror
preventsdaily
activity
Hospitalization
Fatigue
Nointerferencewith
activity
Someinterference
withactivity
Significant;
preventsdaily
activity
Hospitalization
Myalgia
Nointerferencewith
activity
Someinterference
withactivity
Significant;
preventsdaily
activity
Hospitalization

SystemicIllness
Mild
(Grade1)
Moderate
(Grade2)
Severe
(Grade3)
PotentiallyLife
Threatening
(Grade4)
Illnessorclinicaladverse
event(asdefined
accordingtoapplicable
regulations)
Nointerferencewith
activity
Someinterference
withactivitynot
requiringmedical
intervention
Preventsdaily
activityand
requiresmedical
intervention
Hospitalization



RV508/WRAIR#2439
Version1.5

03March2020

Page113of145
B.TablesforLaboratoryAbnormalities

Serum*
Mild
(Grade1)
Moderate
(Grade2)
Severe
(Grade3)
PotentiallyLife
Threatening
(Grade4)
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xULN**
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
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
*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.
**ULN”istheupperlimitofthenormalrange.



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Hematology*
Mild
(Grade1)
Moderate
(Grade2)
Severe
(Grade3)
PotentiallyLife
Threatening
(Grade4)
Hemoglobin(Female)-
gm/dL
11.0– 12.0
9.5– 10.9
8.0– 9.4
<8.0
Hemoglobin(Female)
decreasefrombaseline
value- gm/dL
notapplicable
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)
decreasefrombaseline
value– gm/dL
notapplicable
1.6– 2.0
2.1– 5.0
>5.0
WBCIncrease- cell/mm
3
10,800– 15,000
15,001– 20,000
20,001– 25,000
>25,000
WBCDecrease- cell/mm
3
2,500– 3,500
1,500– 2,499
1,000– 1,499
<1,000
LymphocytesDecrease-
cell/mm
3
750– 1,000
500– 749
250– 499
<250
NeutrophilsDecrease–
cell/mm3-Africandescent

NotofAfricandescent
750-999
500-749
250-499
<250
1,500– 2,000
1,000– 1,499
500– 999
<500
Eosinophils- cell/mm
3
650– 1500
1501- 5000
>5000
Hypereosinophilic
PlateletsDecreased-
cell/mm
3
125,000– 140,000
100,000– 124,000
25,000– 99,000
<25,000
PT– increasebyfactor
(prothrombintime)
1.10xULN**
1.11– 1.20xULN
1.21– 1.25xULN
>1.25ULN
PTT– increasebyfactor
(partialthromboplastin
time)
1.10– 1.20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)
*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.
**ULN”istheupperlimitofthenormalrange.


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APPENDIX7:DAIDSTABLEFORGRADINGSEVERITYOFARTHRALGIA
ADVERSEEVENTS
ThefollowingexcerptfromtheDAIDSAEGradingTableCorrected(Version2.1-July2017)
will be used to grade reported events of joint pain (arthralgia). Solicited AEs involving
arthralgias will be graded using the arthralgia criteria whereas unsolicited AEs involving
arthralgiaswillbegradedusingtheappropriaterowbasedonthepresenceofsymptoms.
PARAMETER
GRADE1
MILD
GRADE2
MODERATE
GRADE3
SEVERE
GRADE4
POTENTIALLY
LIFE-
THREATENING
Arthralgia
Jointpain
causing noor
minimal
interferencewith
usualsocial&
functional
activities
Jointpaincausing
greaterthan
minimal
interferencewith
usualsocial&
functional
activities
Jointpain
causinginability
toperformusual
social&
functional
activities
Disablingjointpain
causinginabilityto
performbasicself-
carefunctions
Arthritis
(objectivefindingson
PEcorrespondingto
thejointpain)
Stiffnessorjoint
swellingcausing
no orminimal
interferencewith
usualsocial&
functional
activities
Stiffnessorjoint
swellingcausing
greaterthan
minimal
interferencewith
usualsocial&
functional
activities
Stiffnessorjoint
swellingcausing
inabilityto
performusual
social&
functional
activities
Disablingjoint
stiffnessorswelling
causinginabilityto
performbasicself-
carefunctions


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APPENDIX9:ROLESANDRESPONSIBILITIES
PrincipalInvestigator
The PI is responsible for the conduct of the RV 508 study at MUWRP. This is the person
designatedastakingoverallresponsibilitywithintheteamofresearchersfortheconductand
reporting of the RV 508 study. The PI will help prepare study reports and article(s) for
publicationincollaborationwiththeprotocolteam.Inaddition,thePIisresponsiblefortheday-
to-dayrunningoftheresearchproject.
ThePIisresponsibleforensuringthat:
· Thedignity,rights,safetyandwell-beingofparticipantsaregivenpriorityatalltimes.
· ThestudyhasobtainedIRBapprovalpriortocommencement
· AllnecessarysubmissionsaremadetothelocalIRB,asapplicable
· ThestudywillbeconductedbythePIpersonallyand/ormembersofhis/herresearchteam
· Eachmemberoftheresearchteam,includingPI,whohasdirectinvolvementwithresearch
participantsand/orperson-identifiabledata,hascompletedallrequiredtraining
· Proceduresareinplacetoensurecollectionofhighquality,accuratedata
· SeriousAdverseEventsandunanticipatedproblemswillbereportedtotherequiredIRBs
andPSRT
· Accuraterecordswillbemaintainedandmadeavailableasrequired
· ContinuingReviewReportingrequirementsarecompleted
· CounselingoccursforparticipantsonHIVandpregnancy
· Theconsentingofparticipantsisdonecorrectlyandpriortoanystudyprocedures
AssociateInvestigators
To actforthePI when thelatter isunableto discharge their responsibilities owing totravel,
leave,deployment,orotherextenuatingcircumstances.
ToassistthePIinallaspectsofprotocolexecution.
StudyPharmacist
· Responsibleforadministering,dispensing,andaccountabilityofstudydrug;assessmentand
managementofadverseevents;andreviewofarisingdataqueries.

LaboratoryInvestigator
· LaboratoryInvestigatorsupervisesclinical(CAPcertified)andresearchlaboratoryactivities
forthestudy.
· Laboratoryinvestigatorswillnothavecontactwithstudyparticipantsorpersonalidentifiers
andagreenottoattempttoobtainanyindividuallyidentifiableparticipantdata

DoDResearchMonitor
The DoD Research Monitor may perform oversight functions (e.g. observe recruitment,
enrollmentprocedures,andtheconsentprocessforparticipants;overseestudyinterventionsand
interactions; review monitoring plans and UPIRTSO reports; oversee data collection, and
analysis)andreporttheirobservationsandfindingstotheIRB.TheDoDresearchmonitormay
discuss the research protocol with the investigators, interview participants, and consult with
othersoutsideofthestudyabouttheresearch.Theresearchmonitorshallhaveauthoritytostopa
researchprotocolinprogress,removeindividualparticipantsfromaresearchprotocol,andtake

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whateverstepsarenecessarytoprotectthesafetyandwell-beingofparticipantsuntiltheIRBs
can assess the monitor's report. Research Monitors shall have the responsibility to promptly
report their observations and findings to the IRB. The DoD Research Monitor is required to
review allunanticipated problems involvingrisks to subjects or others, serious adverse event
(SAE) reports, and all participant deaths. The DoD Research Monitor at a minimum must
comment ontheoutcomesof theevent orproblemand incaseofaserious adverseevent or
death, comments on the relationship to participation in the study. They must also indicate
whetherhe/sheconcurswiththedetailsofthereportprovidedbythePI.
TheDoDResearchMonitorshouldreviewallinitialreportsforSAEs,unanticipatedproblems
involvingriskstosubjectsorothers,andallparticipantdeathsinatimelymanner(within48
hours), and provide their own independent report. The Research Monitor will provide an
unbiasedwrittenreportofallunanticipatedproblemsinvolvingriskstosubjectsorothers,and
relatedSAEsanddeaths,within10workingdaystotheMUSPHIRB,NDA(whereapplicable),
the sponsor, and to the WRAIR HSPB by phone
or by email
AllResearchMonitorreportsforunrelated
SAEsanddeathsshouldbekeptwiththecorrespondingSAEreportsatthestudysite.
TheWRAIRHSPBwillsubmitcopiesofthesereportstotheUSAMRDCORPHRPOasper
SOPUWZ-C-636.
INDMedicalOfficer
TheINDMedicalOfficerreviewsandkeepsabreastofadverseeventsandstudypausesthatmay
occur during the study (all adverse events, including deaths and serious or unexpected side
effects,arereportedtotheINDMedicalOfficerviathePI)inordertoensureaccurateandtimely
reportingtotheFDA.
ClinicalResearchStaff
Undertheguidanceandsupervisionoftheinvestigator,thedutiesoftheClinicalResearchStaff
mayincludethefollowing:
· Assistingintrainingothersitepersonnelandothermedicalstaffinunderstandingand
implementingtheprotocol
· Recruitingandscreeningthepotentialstudyparticipantsaccordingtotheprotocol'sinclusion
andexclusioncriteria
· Maintainingadequatesourcedocumentation(anydocument,orrecordwhereparticipantdata
arefirstrecorded).AlldatanotedintheCRFshouldbeverifiablebysupportingsource
documentation[21CFR312.62(b)]
· CompletingtheCRFsforthestudyaccuratelyandcompletelyasdeterminedbythe
investigator
· Maintainingrecordsofparticipantstatusinthestudybyusingtoolssuchastheenrollment
logCRFs,etc.
WRAIR/MHRP/VRCConsultants
· WillserveasaliaisonbetweenthesiteandSponsor
· Responsibleforprovidinginputforthestudydesignandprotocoldevelopment
· Tooverseetheprocessofstudyimplementation,management,andmonitoringtoinclude
datacollection

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· Serveastechnicaladvisorsandsubjectmatterexpertsforstudyexecution
· Agreenottoattempttoobtainanyindividuallyidentifiableparticipantdata
VRCINDRepresentatives
· WillserveasthepointofcontactonbehalfofthesponsorfortheIND
· ResponsibleforensuringcompliancewiththeprotocolandapplicableUSFDAregulations
· Assumestheresponsibilitiesofthesponsorasdetailedin21CFR312SubpartD
· Willnothavecontactwithstudyparticipantsandagreenottoattempttoobtainany
individuallyidentifiableparticipantdata


RV508/WRAIR#2439
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
03March2020

Page124of145
APPENDIX10:DIARYCARD



RV 508/WRAIR #2439 
 
Version 1.5 
 
Page 1 of 11 
03 March 2020 









RV 508 Participant Diary Card 



Makerere University Walter Reed Project 
Kampala, Uganda 



Version 1.5 
03 March 2020 


Participant ID 

 










	




	
	
				
	 !"#$"	
%""&"#$"' ""&$($()*&*&
$!$
%$+&"#$"', -"-$$!$'--$ &$&
()&&$&$!$
%#$$"#$"', +-$- &$-&()
&&$&$!$
				
Injection Site Pain Severity Scale 
 
 
			 		!		"	
#		
 .$"$(-$#$/-"$0$
 1$ &$$$&$!$ *" $(-$#$$
$"$/"0($#$ +&(2"&&")$$"$
 &, &$$/0$"$
  $(&&/-0-$-/-0#$&--
" "$$--
	
 
 

RV 508/WRAIR #2439 
 
Version 1.5 
 
Page 3 of 11 
03 March 2020 
Participant ID

Day of Vaccination 
 
Date: ____/ ________/__________ (dd/mmm/yyyy)  
 
The evening of the day of Vaccination: 
 
Temp: __________ (oral, °C) Time Taken: ___________ PM 
 
If you have a fever and wish to take your temperature again, record your additional temperature: 
Temp: ________ (oral, °C) Time Taken: _______ AM / PM (circle) 
 
Temp: ________ (oral, °C) Time Taken: _______ AM / PM (circle) 
 
Are you taking any medication?  
Yes 
No 
If yes, please list medication(s): 
 
Please use the symptom scale at the bottom of the page 
Gen. Symptoms 
None 
Mild 
Moderate 
Severe 
Joint Pain 
 
 
 
 
 
Feeling Unwell 
 
 
 
 
 
Muscle Aches (not at 
injection site) 
 
 
 
 
Headache 
 
 
 
 
 
Chills 
 
 
 
 
 
Nausea 
 
 
 
 
 
 
Injection Site 
Symptoms 
None 
Mild 
Moderate 
Severe 
Local Pain 
 
 
 
 
 
Swelling  
Measure in cm 
__ __. __ cm  
 
Please record in cm, the largest width 
measurement of the swelling 
(Example: 2.5 cm) 
Redness  
Measure in cm 
__ __. __ cm  
 
Please record in cm, the largest width 
measurement of the redness 
(Example: 2.5 cm) 
 
Symptoms Severity Scale 
None = no symptoms 
Mild = minimal symptoms; cause minimal or no interference with work, school, or self care activities. 
Moderate = notable symptoms; required modification in activity or medication; did not result in loss of work or cancellation of 
social activities. 
Severe = incapacitating symptoms; requiring bed rest and/or resulted in loss of work or cancellation of social activities. 
For any problems call: 
 
Injection Site Pain Severity Scale 
None = no pain 
Mild = minimal pain; no limitation of use of arm 
Moderate = notable pain; some limitation of use of arm 
Severe = extreme pain; complete limitation of use of arm 

RV 508/WRAIR #2439 
 
Version 1.5 
 
Page 4 of 11 
03 March 2020 
Participant ID

Day 1 after Vaccination 
 
Date: ____/ ________/__________ (dd/mmm/yyyy) 
 
Temp: __________ (oral, °C) Time Taken: ___________ AM / PM (circle) 
 
If you have a fever and wish to take your temperature again, record your additional temperature: 
Temp: ________ (oral, °C) Time Taken: _______ AM / PM (circle) 
 
Temp: ________ (oral, °C) Time Taken: _______ AM / PM (circle) 
 
Are you taking any medication? 
Yes 
No 
If yes, please list medication(s): 
 
Please use the symptom scale at the bottom of the page 
Gen. Symptoms 
None 
Mild 
Moderate 
Severe 
Joint Pain 
 
 
 
 
 
Feeling Unwell 
 
 
 
 
 
Muscle Aches (not at 
injection site) 
 
 
 
 
Headache 
 
 
 
 
 
Chills 
 
 
 
 
 
Nausea 
 
 
 
 
 
 
Injection Site 
Symptoms 
None 
Mild 
Moderate 
Severe 
Local Pain 
 
 
 
 
 
Swelling  
Measure in cm 
__ __. __ cm 
Please record in cm, the largest width 
measurement of the swelling 
(Example: 2.5 cm) 
Redness  
Measure in cm 
__ __. __ cm 
Please record in cm, the largest width 
measurement of the redness 
(Example: 2.5 cm) 
 
Symptoms Severity Scale 
None = no symptoms 
Mild = minimal symptoms; cause minimal or no interference with work, school, or self care activities. 
Moderate = notable symptoms; required modification in activity or medication; did not result in loss of work or cancellation of 
social activities. 
Severe = incapacitating symptoms; requiring bed rest and/or resulted in loss of work or cancellation of social activities. 
For any problems call: 
 
Injection Site Severity Scale 
None = no symptoms 
Mild = minimal pain; no limitation of use of arm 
Moderate = notable pain; some limitation of use of arm 
Severe = extreme pain; complete limitation of use of arm 

RV 508/WRAIR #2439 
 
Version 1.5 
 
Page 5 of 11 
03 March 2020 
Participant ID

Day 2 after Vaccination 
 
Date: ____/ ________/__________ (dd/mmm/yyyy) 
 
Temp: __________ (oral, °C) Time Taken: ___________ AM / PM (circle) 
 
If you have a fever and wish to take your temperature again, record your additional temperature: 
Temp: ________ (oral, °C) Time Taken: _______ AM / PM (circle) 
 
Temp: ________ (oral, °C) Time Taken: _______ AM / PM (circle) 
 
Are you taking any medication?  
Yes 
No  
If yes, please list medication(s): 
 
Please use the symptom scale at the bottom of the page 
Gen. Symptoms 
None 
Mild 
Moderate 
Severe 
Joint Pain 
 
 
 
 
 
Feeling Unwell 
 
 
 
 
 
Muscle Aches (not at 
injection site) 
 
 
 
 
Headache 
 
 
 
 
 
Chills 
 
 
 
 
 
Nausea 
 
 
 
 
 
 
Injection Site 
Symptoms 
None 
Mild 
Moderate 
Severe 
Local Pain 
 
 
 
 
 
Swelling  
Measure in cm 
__ __. __ cm 
Please record in cm, the largest width 
measurement of the swelling 
(Example: 2.5 cm) 
Redness  
Measure in cm 
__ __. __ cm 
Please record in cm, the largest width 
measurement of the redness 
(Example: 2.5 cm) 
 
Symptoms Severity Scale 
None = no symptoms 
Mild = minimal symptoms; cause minimal or no interference with work, school, or self care activities. 
Moderate = notable symptoms; required modification in activity or medication; did not result in loss of work or cancellation of 
social activities. 
Severe = incapacitating symptoms; requiring bed rest and/or resulted in loss of work or cancellation of social activities. 
For any problems call: 
 
Injection Site Severity Scale 
None = no symptoms 
Mild = minimal pain; no limitation of use of arm 
Moderate = notable pain; some limitation of use of arm 
Severe = extreme pain; complete limitation of use of arm 

RV 508/WRAIR #2439 
 
Version 1.5 
 
Page 6 of 11 
03 March 2020 
Participant ID

Day 3 after Vaccination 
 
Date: ____/ ________/__________ (dd/mmm/yyyy) 
 
Temp: __________ (oral, °C) Time Taken: ___________ AM / PM (circle) 
 
If you have a fever and wish to take your temperature again, record your additional temperature: 
Temp: ________ (oral, °C) Time Taken: _______ AM / PM (circle) 
 
Temp: ________ (oral, °C) Time Taken: _______ AM / PM (circle) 
 
Are you taking any medication? 
Yes 
No  
If yes, please list medication(s): 
 
Please use the symptom scale at the bottom of the page 
Gen. Symptoms 
None 
Mild 
Moderate 
Severe 
Joint Pain 
 
 
 
 
 
Feeling Unwell 
 
 
 
 
 
Muscle Aches (not at 
injection site) 
 
 
 
 
Headache 
 
 
 
 
 
Chills 
 
 
 
 
 
Nausea 
 
 
 
 
 
 
Injection Site 
Symptoms 
None 
Mild 
Moderate 
Severe 
Local Pain 
 
 
 
 
 
Swelling  
Measure in cm 
__ __. __ cm 
Please record in cm, the largest width 
measurement of the swelling 
(Example: 2.5 cm) 
Redness  
Measure in cm 
__ __. __ cm 
Please record in cm, the largest width 
measurement of the redness 
(Example: 2.5 cm) 
 
Symptoms Severity Scale 
None = no symptoms 
Mild = minimal symptoms; cause minimal or no interference with work, school, or self care activities. 
Moderate = notable symptoms; required modification in activity or medication; did not result in loss of work or cancellation of 
social activities. 
Severe = incapacitating symptoms; requiring bed rest and/or resulted in loss of work or cancellation of social activities. 
For any problems call: 
 
Injection Site Severity Scale 
None = no symptoms 
Mild = minimal pain; no limitation of use of arm 
Moderate = notable pain; some limitation of use of arm 
Severe = extreme pain; complete limitation of use of arm 

RV 508/WRAIR #2439 
 
Version 1.5 
 
Page 7 of 11 
03 March 2020 
Participant ID

Day 4 after Vaccination 
 
Date: ____/ ________/__________ (dd/mmm/yyyy) 
 
Temp: __________ (oral, °C) Time Taken: ___________ AM / PM (circle) 
 
If you have a fever and wish to take your temperature again, record your additional temperature: 
Temp: ________ (oral, °C) Time Taken: _______ AM / PM (circle) 
 
Temp: ________ (oral, °C) Time Taken: _______ AM / PM (circle) 
 
Are you taking any medication? 
Yes 
No 
If yes, please list medication(s): 
 
Please use the symptom scale at the bottom of the page 
Gen. Symptoms 
None 
Mild 
Moderate 
Severe 
Joint Pain 
 
 
 
 
 
Feeling Unwell 
 
 
 
 
 
Muscle Aches (not at 
injection site) 
 
 
 
 
Headache 
 
 
 
 
 
Chills 
 
 
 
 
 
Nausea 
 
 
 
 
 
 
Injection Site 
Symptoms 
None 
Mild 
Moderate 
Severe 
Local Pain 
 
 
 
 
 
Swelling  
Measure in cm 
__ __. __ cm 
Please record in cm, the largest width 
measurement of the swelling 
(Example: 2.5 cm) 
Redness  
Measure in cm 
__ __. __ cm 
Please record in cm, the largest width 
measurement of the redness 
(Example: 2.5 cm) 
 
Symptoms Severity Scale 
None = no symptoms 
Mild = minimal symptoms; cause minimal or no interference with work, school, or self care activities. 
Moderate = notable symptoms; required modification in activity or medication; did not result in loss of work or cancellation of 
social activities. 
Severe = incapacitating symptoms; requiring bed rest and/or resulted in loss of work or cancellation of social activities. 
For any problems call: 
 
Injection Site Severity Scale 
None = no symptoms 
Mild = minimal pain; no limitation of use of arm 
Moderate = notable pain; some limitation of use of arm 
Severe = extreme pain; complete limitation of use of arm 

RV 508/WRAIR #2439 
 
Version 1.5 
 
Page 8 of 11 
03 March 2020 
Participant ID

Day 5 after Vaccination 
 
Date: ____/ ________/__________ (dd/mmm/yyyy) 
 
Temp: __________ (oral, °C) Time Taken: ___________ AM / PM (circle) 
 
If you have a fever and wish to take your temperature again, record your additional temperature: 
Temp: ________ (oral, °C) Time Taken: _______ AM / PM (circle) 
 
Temp: ________ (oral, °C) Time Taken: _______ AM / PM (circle) 
 
Are you taking any medication? 
Yes 
No  
If yes, please list medication(s): 
 
Please use the symptom scale at the bottom of the page 
Gen. Symptoms 
None 
Mild 
Moderate 
Severe 
Joint Pain 
 
 
 
 
 
Feeling Unwell 
 
 
 
 
 
Muscle Aches (not at 
injection site) 
 
 
 
 
Headache 
 
 
 
 
 
Chills 
 
 
 
 
 
Nausea 
 
 
 
 
 
 
Injection Site 
Symptoms 
None 
Mild 
Moderate 
Severe 
Local Pain 
 
 
 
 
 
Swelling  
Measure in cm 
__ __. __ cm 
Please record in cm, the largest width 
measurement of the swelling 
(Example: 2.5 cm) 
Redness  
Measure in cm 
__ __. __ cm 
Please record in cm, the largest width 
measurement of the redness 
(Example: 2.5 cm) 
 
Symptoms Severity Scale 
None = no symptoms 
Mild = minimal symptoms; cause minimal or no interference with work, school, or self care activities. 
Moderate = notable symptoms; required modification in activity or medication; did not result in loss of work or cancellation of 
social activities. 
Severe = incapacitating symptoms; requiring bed rest and/or resulted in loss of work or cancellation of social activities. 
For any problems call: 
 
Injection Site Severity Scale 
None = no symptoms 
Mild = minimal pain; no limitation of use of arm 
Moderate = notable pain; some limitation of use of arm 
Severe = extreme pain; complete limitation of use of arm 

RV 508/WRAIR #2439 
 
Version 1.5 
 
Page 9 of 11 
03 March 2020 
Participant ID

Day 6 after Vaccination 
 
Date: ____/ ________/__________ (dd/mmm/yyyy) 
 
Temp: __________ (oral, °C) Time Taken: ___________ AM / PM (circle) 
 
If you have a fever and wish to take your temperature again, record your additional temperature: 
Temp: ________ (oral, °C) Time Taken: _______ AM / PM (circle) 
 
Temp: ________ (oral, °C) Time Taken: _______ AM / PM (circle) 
 
Are you taking any medication? 
Yes 
No  
If yes, please list medication(s): 
 
Please use the symptom scale at the bottom of the page 
Gen. Symptoms 
None 
Mild 
Moderate 
Severe 
Joint Pain 
 
 
 
 
 
Feeling Unwell 
 
 
 
 
 
Muscle Aches (not at 
injection site) 
 
 
 
 
Headache 
 
 
 
 
 
Chills 
 
 
 
 
 
Nausea 
 
 
 
 
 
 
Injection Site 
Symptoms 
None 
Mild 
Moderate 
Severe 
Local Pain 
 
 
 
 
 
Swelling  
Measure in cm 
__ __. __ cm 
Please record in cm, the largest width 
measurement of the swelling 
(Example: 2.5 cm) 
Redness  
Measure in cm 
__ __. __ cm 
Please record in cm, the largest width 
measurement of the redness 
(Example: 2.5 cm) 
Symptoms Severity Scale 
None = no symptoms 
Mild = minimal symptoms; cause minimal or no interference with work, school, or self care activities. 
Moderate = notable symptoms; required modification in activity or medication; did not result in loss of work or cancellation of 
social activities. 
Severe = incapacitating symptoms; requiring bed rest and/or resulted in loss of work or cancellation of social activities. 
For any problems call: 
 
Injection Site Severity Scale 
None = no symptoms 
Mild = minimal pain; no limitation of use of arm 
Moderate = notable pain; some limitation of use of arm 
Severe = extreme pain; complete limitation of use of arm 

RV 508/WRAIR #2439 
 
Version 1.5 
 
Page 10 of 11 
03 March 2020 
Participant ID

Day 7 after Vaccination 
 
Date: ____/ ________/__________ (dd/mmm/yyyy) 
 
Temp: __________ (oral, °C) Time Taken: ___________ AM / PM (circle) 
 
If you have a fever and wish to take your temperature again, record your additional temperature: 
Temp: ________ (oral, °C) Time Taken: _______ AM / PM (circle) 
 
Temp: ________ (oral, °C) Time Taken: _______ AM / PM (circle) 
 
Are you taking any medication? 
Yes 
No  
If yes, please list medication(s): 
 
Please use the symptom scale at the bottom of the page 
Gen. Symptoms 
None 
Mild 
Moderate 
Severe 
Joint Pain 
 
 
 
 
 
Feeling Unwell 
 
 
 
 
 
Muscle Aches (not at 
injection site) 
 
 
 
 
Headache 
 
 
 
 
 
Chills 
 
 
 
 
 
Nausea 
 
 
 
 
 
 
Injection Site 
Symptoms 
None 
Mild 
Moderate 
Severe 
Local Pain 
 
 
 
 
 
Swelling  
Measure in cm 
__ __. __ cm 
Please record in cm, the largest width 
measurement of the swelling 
(Example: 2.5 cm) 
Redness  
Measure in cm 
__ __. __ cm 
Please record in cm, the largest width 
measurement of the redness 
(Example: 2.5 cm) 
Symptoms Severity Scale 
None = no symptoms 
Mild = minimal symptoms; cause minimal or no interference with work, school, or self care activities. 
Moderate = notable symptoms; required modification in activity or medication; did not result in loss of work or cancellation of 
social activities. 
Severe = incapacitating symptoms; requiring bed rest and/or resulted in loss of work or cancellation of social activities. 
For any problems call: 
 
Injection Site Severity Scale 
None = no symptoms 
Mild = minimal pain; no limitation of use of arm 
Moderate = notable pain; some limitation of use of arm 
Severe = extreme pain; complete limitation of use of arm 

RV 508/WRAIR #2439 
 
Version 1.5 
 
Page 11 of 11 
03 March 2020 
Participant ID
 
If you have any of the General or Injection Site Symptoms that is still ongoing after day 7, please complete 
stop dates below. 
 
General Symptoms 
Date the  
Symptom Ended 
Maximum severity after day 7  
(Mild, moderate or severe)  
Joint Pain 
 
 
Feeling Unwell 
 
 
 
Muscle Aches (not at injection site) 
 
 
Headache 
 
 
Chills 
 
 
Nausea 
 
 
 
 
Injection Site Symptoms 
Date the 
Symptom Ended 
Maximum severity after day 7  
(Mild, moderate or severe)  
Local pain 
 
 
Swelling 
Measure in cm 
 
__ __. __ cm 
Redness 
Measure in cm 
 
__ __. __ cm 
Are you or have you taken any medication after day 7? If so, please record the name of the medication and 
the date you stopped taking the medication below, if applicable. 
Name of Medication 
Date You Stopped 
Medication 
 
 
 
 
 
 
 
 
 
 


RV508/WRAIR#2439
Version1.5

03March2020

Page136of145
APPENDIX11:RECRUITMENTMATERIALS



RV 508 Flyer 
RV 508/WRAIR #2439 
 
Version 1.5 
Recruitment Flyer 
 
03 March 2020 
 
 
 
FLYER MESSAGE: 
 
ARE YOU INTERESTED IN JOINING AN EBOLA VACCINE 
STUDY? 
 
 
If you are aged 18-50 years and in good health  
 
 Call toll free number 0800-200058 for more information 
 
OR 
 
Visit Makerere University Walter Reed Project offices 
 
 
 
Join Ugandan Scientists in the Search for Vaccines Against Ebloa 

RV 508 Newspaper Advert 
RV508/WRAIR #2439 
Version 1.5 
Newspaper Advert 
03 March 2020 
NEWSPAPER ADVERT: Message concept: 
VOLUNTEERS NEEDED NOW TO TEST INVESTIGATIONAL (Study) 
VACCINE FOR THE PREVENTION OF EBOLA 
 
The vaccine DOES NOT contain any virus and CAN NOT cause Ebola  
 
Volunteers must be aged 18- 50 years and in good health 

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-.#)&%/""+

RV 508 Radio Announcement 
RV 508/WRAIR #2439 
 
Version 1.5 
Radio Announcement 
 
03 March 2020 
 
 
 
 
RADIO ANNOUNCEMENT 
 
Message concept: 
 
Makerere University Walter Reed Project is looking for volunteers to test an 
Investigational Vaccine for the PREVENTION of Ebola. 
 
The Vaccine DOES NOT contain any virus and CAN NOT cause Ebola  
(Repeat) 
 
Interested individuals between the ages of 18 – 50 and in good health are invited to an 
Information Seminar this _________________ at _______ pm, at the Makerere University 
Walter Reed Project offices 
 
 
OR can call toll free number 
 for directions/ more information (repeat phone 
number) 
 
 
 
JOIN UGANDAN SCIENTISTS IN THE SEARCH FOR A VACCINE AGAINST 
EBOLA  
 

	

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RV508/WRAIR#2439
Version1.5

03March2020

Page142of145
APPENDIX12:APPOINTMENT/EMERGENCYCONTACTCARD



RV 508/WRAIR #2439 
 
Version 1.5 
Emergency Contact/ Appointment Card 
 
03 March 2020 
MUWRP 
MAKERERE UNIVERSITY WALTER REED PROJECT 
APPOINTMENT CARD 
Name: _________________________________________________ 
Date: ____________________  
Time: __________________ 
For Emergencies that occur between 8:00am and 5:00pm, please call 
 For Emergencies that occur before 8:00am or after 
5:00pm, please call 
 

RV508/WRAIR#2439
Version1.5

03March2020

Page144of145
APPENDIX13:LISTOFEXTERNALCOLLABORATORS



RV508/WRAIR#2439

Version1.5
MainStudyICF
Page1of12
03March2020
MAINSTUDYINFORMEDCONSENTFORM

StudyTitle:RV508,“APhaseIOpen-Label,Dose-EscalationClinicalTrialtoEvaluatetheSafety,
TolerabilityandImmunogenicityofTwoDosesofanEbolaSudanChimpanzee
AdenovirusVectorVaccine,VRC-EBOADC086-00-VP(cAd3-EBOS),inHealthy
Adults”
Sponsor:NationalInstitutesofHealth(NIH),NationalInstituteofAllergyandInfectiousDiseases
(NIAID)VaccineResearchCenter(VRC)
FundingAgencies:NIH,theU.S.MilitaryHIVResearchProgram(MHRP)andtheU.S.Departmentof
Defense(DoD)
StudyProductProvidedby:NIH/NIAID/VRC
StudyConductedby:MakerereUniversityWalterReedProject(MUWRP)
PrincipalInvestigator:BettyMwesigwa,MBChB,MScClinicalTrials
INTRODUCTION
Youarebeinginvitedtoconsiderparticipatinginthisstudybecauseyouareahealthypersonwhomay
meetthecriteriatojointhisstudy.Beforedecidingtoparticipateinthisstudy,pleasereadthisdocument
thoroughly.Indoingso,youwillunderstandthepurposeanddetailsofthisstudy.
Beforeyoudecidewhetherornottotakepartinthisstudy,wewouldliketoexplainthepurposeofthe
research study, how it may help you or others, any risks associated with participation, and our
expectations of you. This process is called informed consent. It is important that you know the
following:
a. Takingpartisofyourownfreewill(entirelyvoluntary).
b. Ifyoudecidenottoparticipateyouwillnotloseanyofthebenefitsorrightsyouwouldnormally
haveorbedisadvantagedinanyway.
c. Youmaydecidenottoparticipateinthestudyoryoumaydecidetostopparticipatinginthe
studyatanytimewithoutlossofanymedicalcaretowhichyouareentitlednoworinthefuture.
Pleaseaskquestionsaboutanythingyoudonotunderstandatanytime.Theclinicstaffwilltalktoyou
abouttheinformationinthisform.Youcantakeasmuchtimeasyouneedtoreviewthisformand
discussyourstudyparticipationwithyourfamily,friends,andcommunityasyoufeelcomfortableand
appropriate,inordertodecidewhetherornotyouwouldliketoparticipate.Ifyoudecidetoparticipate
inthisstudy,youwillreviewthisdocumentwithastudystaffandwillberequestedtosignanddateat
theendofthisformtoshowthatyourquestionshavebeenansweredandthatyouwanttotakepartin
thestudy.Acopyofthissigned/markedinformedconsentwillbeprovidedtoyou.Thisconsentmustbe
signed/markedbeforeanystudyproceduresareperformed.

RV508/WRAIR#2439
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03March2020
Youwillalsohavetheopportunitytoconsentforfuture(currentlyunknown)useofyoursamples,and
genetictesting.Thesewillbeexplainedtoyou,andyouwillsignaseparateconsentforeach.
ThetechnicalnameofthestudyvaccineisVRC-EBOADC086-00-VP,butwewillrefertoitas“cAd3-
EBOS”orsimplyasthe“Ebolavaccine.”ThestudyvaccinedoesnotcontainliveorkilledEbolavirus.
ItisimpossibleforthestudyvaccinetogiveyouanEbolavirusinfection.
ThisresearchstudyisfundedbytheU.SDoDandtheNIAID/NIH.TheMUWRPisconductingthis
researchstudyincollaborationwiththeU.S.MHRPandNIAID/NIHinKampala,Uganda.
PURPOSEANDBACKGROUND
ThisresearchstudywillevaluateanexperimentalvaccinefortheEbolaVirus.“Experimental”means
thatitisnotknownifthevaccineworkstopreventtheSudanstrainofEbolaVirusDisease(EVD).
Since it is not known if the vaccine works, it has not been approved by the US Food and Drug
Administration(FDA)ortheUgandaNationalDrugAuthority(NDA).Vaccinesaresubstancesusedto
createimmuneresponses(resistance)toaninfectioninordertopreventadisease.Immuneresponsesare
how your body recognizes and defends itself against bacteria, viruses, and substances that may be
harmfultothebody.
ThemainpurposeofthisstudyistoseeiftheexperimentalEbolavaccineissafeandifitcausesany
sideeffects.Anothergoalistostudybloodsamplesinthelabtoseeifandhowtheimmunesystem
respondsinpeoplewhoreceivethisvaccine.
TheEbolaviruswasdiscoveredin1976.ItisnamedafterariverinAfricaclosetowheretheviruswas
firstdiscovered.BatsincertainpartsofAfricacarrythevirus.EVDstartswithfeverandmuscleaches.
Moreseveresymptomsarebreathingproblems,severebleeding,kidneyproblems,andshock(lossof
bloodpressure).Theinfectionmaybemild,butitcanalsoleadtodeath.Thefirsttwooutbreaksof
Ebola Hemorrhagic Fever in Africa in 1976 caused 340 deaths. In Africa, when there have been
outbreaksofEbolavirus,50%to90%ofinfectedpeoplehavedied.
STUDYVACCINE
TheexperimentalEbolavaccineinthisstudywasdevelopedinalaboratorybytheVRCattheNIH,
locatedinBethesda,MarylandUSA.Theexperimentalvaccinehaspreviouslybeengiventohumansin
combinationwithotherEbolavaccineproducts,butnotbyitself.
ThecAd3-EBOSvaccineusesanothervirus,calledchimpanzeeAdenovirus3(cAd3),todeliverapiece
oftheEbolaSudanvirustocellsinyourbody.Theadenovirususedtomakethevaccineisfromastrain
thatinfectschimpanzees.Thisstrainofadenovirushasbeentestedinpeoplebeforeanddoesnotcause
humanadenovirusinfections.Itisfurtherchangedtomakesureitcannotreproduceinahumanbody.
OncetheEbolaSudanviruspieceisdeliveredtothecellsinyourbody,yourbodywillthenmakean
immune response. You cannot become infected with or infect someone else with either Ebola or
adenovirusfromreceivingthestudyvaccine.

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03March2020
STUDYPARTICIPATION
Ifyouagreetotakepartinthestudyyouwillreceiveonestudyinjectionattheenrollmentvisit(Visit2).
Thevaccineinjectionwillbegivenusinganeedleandsyringeintoanupperarmmuscle.Thisiscalled
anintramuscular(IM)injection.
About40participantswillbeenrolledintothisstudyandwillbedividedinto2groups.Bothgroupswill
have about 20 participants. Participants in Group 1 will receive a low dose of the vaccine and
participantsinGroup2willreceiveahigherdose.EnrollmentintoGroup2willnotbeginuntilaftera
safety review is completed for participants who received the lower dose of the vaccine and it is
determinedtobesafe.ThehigherdoseoftheexperimentalEbolaSudanvaccineisbasedondoselevels
foundtobesafeinpreviousstudiesofsimilarvaccinesthatusedthechimpanzeeadenovirus.Ifyou
wouldliketoknowwhichgroupyouarein,pleaseaskthestudyclinician.
VaccinationSchedule:
RV508StudyGroups
Group
Participants
VaccineDose
1
20
cAd3-EBO S at1x1010 PUIM
2
20
cAd3-EBO S at1x1011 PUIM
STUDYDURATION
Participation inthisstudy willlastfor about 48weeks(almost 1year)from thetimeof enrollment.
Therewillbe1screeningvisitand10studyvisits(1visitforvaccinationand9visitsforfollow-up).
However,thesedonotincludeadditionalappointmentsifyouhaveanysideeffectsandifthestudyteam
requestsyoutocometotheclinic.Thescreeningandvaccinationvisitswilleachtakeapproximately2-3
hours.Otherappointmentswilltakeapproximately1-2hours.Ascheduleofeventsdetailingyourvisits
willbeprovidedtoyou.
STUDYPROCEDURES
a) HowdoIjoininthisstudy?
Youwillhavetosignthisformacknowledgingthatyouhavereadtheform,thatallyourquestionshave
beenansweredsatisfactorily,andthatyouagreetoparticipateinthisstudy.
Youmaytakepartinthisstudyifyouareahealthy,maleorfemalevolunteer,betweenages18and50
withabodymassindex(aratiobasedonyourweightandheight)<40,availableforaperiodof48
weeks, able to provide proof of identity, willing to have the vaccine injection site and any vaccine
reactionsonyourskinphotographed,andagreetoclinicstaffvisitingyourhome(asmaybenecessary).
Youmustalsobeabletoreadthisconsentform,understandandcompletethisinformedconsentprocess,
successfullycompleteanAssessmentofUnderstanding(toseeifyouunderstandtheinformationinthis
form), and be free of significant medical problems. Blood tests will be done to measure your
hemoglobin(amountofblood),yourwhitebloodcells,andyourliverandkidneyfunction.Femaleswill
alsoberequiredtoundergopregnancytesting,tonotbepregnant,tonotbebreastfeeding,andtoplan
nottobecomepregnantforatleast6monthsaftervaccination.Femalesmustalsoagreetouseabirth
controlmethodforatleast21dayspriortovaccinationandforatleast6monthsaftervaccination.

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YoucannotparticipateinthisstudyifyoureceivedanexperimentalEbolaorMarburgvaccineorhave
received a different cAd3 experimental vaccine. You also cannot participate if you have any of the
followingconditions:
· A history of a serious allergic reaction to any vaccines or allergic reaction to drugs like
gentamycin,neomycinorstreptomycin
· Anautoimmunediseaseordeficiencyorchronicallyrecurringhives,asplenia(lackofnormal
spleenfunction)orahistoryofangioedema(facialswelling)
· HIVinfection
· Activesyphilisinfection
· Diabetes(typeIorII)
· Thyroiddiseasethatisnotwellcontrolled
· Highbloodpressureorasthmathatisnotwellcontrolled
· Ableedingproblemordisorder
· Cancer
· Ahistoryofseizuresortreatmentforseizuredisorderinthepast3years
Youalsocannotparticipateifyouhavereceivedanyofthefollowing:
· Drugsthatmaymodifyyourimmunesystemwithin14dayspriortoenrollmentsuchas
prednisoneordexamethasone
· Bloodproductswithin112days(16weeks)priortoenrollment
· Any“live-attenuated”vaccine(e.g.,oralpolio,yellowfever,measles,etc.)within28daysprior
toenrollmentinthepresentstudyoranyothervaccinewithin14dayspriortoenrollment
· Experimentalresearchdrugswithin28dayspriortoenrollmentinthepresentstudy
· DrugsfortreatingorpreventingTuberculosis

You also may not participate in the study if the Investigators think you may have a history of any
condition(s)thatmayinterferewithyourfullparticipationinthestudyorthatmayimpairyourabilityto
provideinformedconsent.
Itisimportanttoremindyouthattoparticipateinthisstudyyouneedtoagreetohomevisitsbythe
clinicstaff.Theclinicstaffmayvisityourhomeiftheyareunabletoreachyoubyphone,inorderto
remindyouofyourscheduledvisitorforfollowup.
b) Screening(Visit1)
Afteryouhavereviewedthestudyconsentformandhaveagreedtoparticipate,thestudystaffwillask
you to complete an Assessment of Understanding (AOU). The AOU will help the study staff to
determine how well you have understood the information about this study and what is required for
participation.Youmustcomplete9outofthe10questionscorrectlyatleastoncein3attempts.Afterthe
AOU,yourmedicalhistorywillberecordedandathoroughphysicalexaminationwillbeperformedon
youbyamemberof thestudystaff.Inaddition, youwill have blood takento checkyour HIVand
syphilisstatus.
A serum(blood)pregnancytestwillberequiredat thescreeningvisitifyouarefemaleandableto
becomepregnant.TheresearchstaffwilltestyourbloodforHIV(humanimmunodeficiencyvirus),the

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virusthat causes AIDS. Prior to this blood test, you willreceivecounseling about HIV, AIDS, and
preventionofHIV.IfyouareHIVinfected,youwillreceiveadditionalinformationaboutHIVandwill
bereferredtoourHIVClinicortheInfectiousDiseaseInstitute(IDI)atMulagooranyotherHIVClinic
ofyourchoice.
Itmaybenecessarytoreturntotheclinicforafollowupappointmentortorepeattestsifthereareany
abnormallaboratoryresults.Ifthephysiciandiscoversanillnessorconditionthatrequirestreatment,
youwillbereferredtoahospitalorclinicthatcanprovidefurtherevaluationortreatment.
If you are eligible for participation in this study, you will be scheduled for an appointment for the
vaccinationvisitwithin56daysofthescreeningdate.Itisimportanttoremindyouthataspartofthe
qualificationforthisstudyyouhaveagreedtopossiblehomevisitsbytheclinicstaff.
c) EnrollmentandFollow-upVisits
Theclinicstaffwillobserveyouforatleast30to60minutesaftertheinjectionattheenrollmentvisit.
Youwillbeaskedtocompleteadiarycardandlookatyourinjectionsiteintheeveningonthedayof
the vaccination and then every day for the next 7 days. You will record your temperature, any
symptoms,anddescribeanyskinchangesattheinjectionsiteeachday.Youwillbeprovidedwitha
thermometertotakeyourtemperatureandrulertomeasureanyinjection-siteskinchanges.Youmay
havetocometotheclinicifyouhaveafeverof38.5˚Corhigherthatlastsmorethan24hours,arash,
hives,ordifficultyinyourusualdailyactivities(suchasgoingtowork,fixingameal,laundry,etc.).
Youwillbeabletoreachastudyinvestigatoratanytimeofdayornightshouldyouhaveanyconcerns.
Ifyoudevelopanysymptomsthatareofconcerntoyouorthestudyteam,itmaybenecessarytocome
tothestudyclinicforanexaminationbeforeyournextscheduledvisit.Itisveryimportantthatyou
followtheinstructionsgiventoyoubytheclinicstaff.Youmayalsoneedtocometotheclinicforany
problemthatthenurseordoctorthinksshouldbecheckedbyexam,bloodorothermedicaltest.
Ateachvisit,youwillbecheckedforanyhealthchangesorproblemssinceyourlastvisit.Youwillbe
askedhowyouarefeelingandwhatmedicationsyoumayhavetaken.Bloodwillbedrawnduringclinic
visitsfortestingofyourhealthandyourimmunesystem.
The amount of blood drawn will vary from about 25 mL (about 5 teaspoons) to about 92 mL (6
tablespoons),dependingonthevisit.Youmightalsobeaskedtohavelaboratorytestsbetweenregular
visits if needed to check your health. The total amount of blood drawn during the 48 weeks of
participationwillbelessthan700mL(about1.5tumpecomugs).
Nomorethanatotalofaboutonetumpecomug(450mL)willbedrawnoverany3-monthperiodduring
thestudy.Femaleparticipantswillalsohavetogiveaurinesampleforpregnancytestatsomevisits.
Youwill beinformedpromptly ifany healthconcerns are identifiedbythetests. Youshould avoid
donatingbloodforatleastoneyearafteryourstudyvaccination.
Thestudyteamwillinformyouoftheresultsfromyourlabtestsandmedicalexaminationatthenext
studyvisit.Incaseswhereanabnormalitymaybeofconcern,theinvestigatorswillnotifyyouassoon
as possible. If any concerning abnormality is detected, you will be referred for appropriate testing,
treatmentandcareasmayberequired.

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d) Samplecollectionduringthestudy
i.
Bloodandurinespecimens:Theinvestigatorswillobtainbloodtotestforanypossibleside
effects as well as evaluate the immune response to the vaccine. Urine collected at study
visitswillbeusedforpregnancytestsforfemalevolunteers.

ii.
HLAandgenetictests:Partofthebloodsamplesforthisstudywillbeusedtoanalyzefor
HLA(‘HumanLeukocyteAntigen’)type.HLAisagroupofproteinspresentonthesurface
ofallcellsinthehumanbodywithanimportantroleintheimmuneresponsetoinfection.
DeterminingHLAtypeisnecessarytobeabletoperformcertainresearchstudies.Wewill
not notify you with the results of this test. The HLA test for this study is not a normal
medicaltestandthetestresultwillnotbeusedfortreatmentpurpose.Youwillbeprovideda
separateformtoconsentorrefusegenetictestingonyoursamples.
WHATWILLHAPPENTOMYSAMPLESAFTERTHISSTUDY?
a) SampleStorage
Duringyourparticipationinthisstudy,bloodsampleswillbecollectedfromyouasalready
explained.Wewillstoreleftoverbloodsamplesinasecurecentralstoragesite(notinthe
clinic)intheUSAforfutureresearchtolearnmoreaboutEbolavirus,vaccines,theimmune
system,and/orothermedicalconditions.Onlysamplesfromparticipantswhohaveprovided
consentforfutureuseoftheirsampleswillbestoredattheendofthisstudy.Ifconsentisnot
provided,thesampleswillbedestroyeduponcompletionoftestsforthisstudy.
Please notethatsampleswillonlybetransferredtoanother countryafterapprovalbythe
UgandaNationalCouncilofScienceandTechnologyandyourpersonalinformationwillnot
bedisclosed/attachedtothesespecimens(asdescribedbelow).
b) FutureStudies
Youwillhavetheopportunitytoreview,askquestionsandprovideconsent(permission)for
storageanduseofyourbloodsamplesforfutureunknownuse,inthe“FutureUseBlood
SampleConsentForm.”Allfutureresearchthatusesstoredsamplesmustbereviewedand
approvedbyanInstitutionalReviewBoard(IRB),whichisacommitteethatisresponsible
foroverseeingthesafety,welfareandrightsofresearchparticipants.
c) SpecimenLabeling
Specimenswillbestoredandlabeledusinganumericbarcodewithoutyournameattached.
Only the site-investigator team is able to connect those numeric codes and your name.
Personal Identification Information will be kept confidentially according to all applicable
lawsandregulations.
POSSIBLERISKSOFSTUDYPARTICIPATION
ThissectiondescribestherisksassociatedwiththeexperimentalEbolaSudanvaccineandotherstudy
procedures. There may be additional risks related to the experimental vaccine that are currently
unknown.These unknown risks could affect youor, if applicable, your unbornchild if youbecome
pregnant.Ifthestudyinvestigatorslearnaboutnewrisksduringthisstudy,thestudyinvestigatorswill
tellyou.

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Possible risks from the injection: Temporary stinging, pain, arm discomfort, redness, soreness,
itchiness, swelling or bruising at the injection site on your arm. There is a very small chance of
infection.
Possible risks from any vaccine: Fever, chills, rash, aches and pains, nausea, headache, dizziness,
fatigue(feelingtired),andmalaise(feelingunwell).Somepeoplehaveallergicreactionstovaccines.
Thesetypesofreactionsareusuallygreatestwithinthefirst24hoursaftervaccinationandmaylast1to
3days.
PossiblerisksoftheexperimentalEbolaSudanvaccine:Therisksoftheexperimentalvaccineare
unknown.Themostcommoncomplaintsinthefirstfewdaysafterreceivingsimilarvaccinesinclude
sore arm, headache, muscle aches and feeling tired. A few people had a fever within a day after
vaccination.
As with any vaccine,there may bea riskof skinrash, hives,or other unknownside effects. If you
developareactiontotheexperimentalvaccineonyourskin,theinvestigatorswilltakepicturesofthe
reactionandthevaccineinjectionsite.Everyeffortwillbemadetoavoidphotographingyourfaceor
any tattoosor birthmarksthat mayidentifyyou inthephotograph. Yournameand otheridentifying
informationwillnotbeassociatedwiththephotograph.Allphotographswillrelateonlytothisstudy
andwillbethepropertyofthesponsor.
TherearecurrentlynovaccinesapprovedforusetoprotectagainstEbolavirusinfection.Receiptofthis
experimentalEbolavaccinemayaffectyourresponsetofuturevaccinesagainstEbola.Itisunknownif
you will develop an immune response, such as antibodies, after vaccination. It is unknown if your
immuneresponse wouldprotect against EVD,have noeffect onprotection,or increaseyour riskof
EVD.Itisalsounknownhowlonganimmuneresponsetothevaccinemaylast.Youshouldcontinueto
takeallprecautionsagainstbeingexposedtobodyfluidsofpeoplewhohaveanEbolavirusinfection.
Unknownsafetyrisks:Theremaybeunknownsideeffectsfromthestudyvaccine–evenseriousor
life-threateningrisks–thatwedonotyetknowabout.Pleasetellthestudystaffaboutanysideeffect
youthinkyouarehavingassoonaspossible.Thisisimportantforyoursafety.
Possible risks of blood drawing: Pain, bleeding, bruising, feeling lightheaded, fainting, or rarely,
infectionatthesitewherethebloodistaken.Tominimizetherisks,trainedhealthcareproviderswill
drawyourblood.
Possiblerisksfromgenetictesting:Unintendedreleaseofinformationcouldbeusedbyinsurersor
employers; discovering a gene that suggests risk of disease for you or your family; discovering
undisclosedfamilyrelationships.Tominimizetherisks,resultswillonlybelabeledwithacode,not
yournameorotheridentifyinginformation.
PossibleriskstoPregnancy:Ifyouarepregnant,breast-feedingorwanttobecomepregnantfrom21
daysbeforevaccinationuntil24weeks(6months)afterthevaccination,youcannotparticipateinthis
study.Wedonotknowthepossibleeffectsofthestudyvaccineontheunbornbabyornursinginfant.
Therefore,womenwhoareabletobecomepregnantmusthaveanegativepregnancytestbeforethe
study vaccination and agree to practice adequate birth control beginning at least 21 days prior to
receiving the study injection until 24 weeks after the injection. Adequate methods of birth control
include: condoms, male or female, with or without a spermicide; diaphragm or cervical cap with

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spermicide;intrauterinedevice;allprescriptionmethods(suchascontraceptivepills,injections,patches
andothers);oramalepartnerwhohaspreviouslyundergoneavasectomy.Youmustnotifytheclinic
staffimmediatelyuponlearningthatyouhavebecomepregnantduringthisstudy.Youmustalsonotify
theclinicifyoususpectthatyoumightbepregnantduringthisstudy.Youwillbeaskedtocontinue
with the planned study follow-up visits for safety purposes and contacted later to learn about the
outcomeofanypregnancythatstartsinthefirst24weeksafterstudyvaccination.
OtherRisks:Youmaynotdonatebloodwhileparticipatinginthisresearchstudyorforoneyearafter
thedateoftheexperimentalvaccineinjection.
YoursampleswillbeshippedtocollaboratorsoutsideofMUWRPtobeanalyzed.Thesesampleswill
onlybelabeledwithyourstudynumber,notyournameorotherpersonalinformation.Sampleswillonly
beshippedafterapprovalfromtheMUWRPIRB.
WHATIFTHERESEARCHERSLEARNNEWINFORMATIONDURINGTHISSTUDY?
Resultsofthisstudyorotherscientificresearchmayaffectyourwillingnesstocontinuetotakepartin
thisstudy.Duringthecourseofthestudy,youwillbeinformedofanysignificantnewfindings(either
goodorbad),suchaschangesintherisksorbenefitsresultingfromparticipationintheresearchornew
alternativestoparticipationthatmightcauseyoutochangeyourmindaboutcontinuinginthestudy.If
new information is provided to you, your consent to continue participating in this study will be re-
obtained.
BENEFITSFROMSTUDYPARTICIPATION
Youwillreceivenodirectbenefitfromparticipatinginthisstudybecausenooneknowsifthevaccine
willwork.However,youandothersmaybenefitinthefuturefromtheinformationthatwillbelearned
fromthestudy.TheresultsofthisstudycouldplayaroleinwhethertheFDAwillapprovethevaccine
forsaleatsometimeinthefuture.Youwillnotreceivemoneyorothercompensationshouldthisoccur.
COMPENSATIONFORSTUDYPARTICIPATION
Youwillbe compensatedUgshs50,000fortimeandinconvenienceassociatedwitheachscheduled
visitanduptoUgshs20,000foreachunscheduledvisit.Unscheduledvisitswillbecompensatedonlyif
thePrincipalInvestigator/designeefindsitnecessary.Otherthanmedicalcarethatmaybeprovidedand
otherpaymentspecificallystatedinthisform,thereisnoothercompensationavailableforyoutaking
partinthisstudy.
PERSONALINFORMATIONCONFIDENTIALITY
ThePrincipalInvestigatoratthisclinic,Dr.BettyMwesigwa,willmaintainresearchrecordsofyour
takingpartinthisstudy.
All study volunteers will receive a study identification (SID) number. An SID is a unique number
assigned to each participant, known only to the study team at the clinic and used to ensure the
confidentialityofresearchinformation.Allyourstudydocuments,samplesandtestresultswillnotbear
your name but will have your SID, the date, study number, group number and study visit number.
Personalidentifyinginformation like yourname and agecollectedat the timeof enrollment will be

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storedinalockablecabinettowhichonlydesignatedstudyteammemberswillhaveaccess.Thesesteps
willensureconfidentialityofyourpersonalinformationandminimizethechancesofitbecomingknown
toothers.
ClinicalandresearchrecordsmaybereviewedbyrepresentativesoftheU.S.ArmyMedicalResearch
andDevelopmentCommand(USAMRDC),OfficeforHumanResearchProtections(OHRP),Human
ResearchProtectionOffice(HRPO),U.S.DoD,WRAIRHumanSubjectsProtectionBranch,Makerere
University School of Public Health IRB, NIAID, the Uganda National Drug Authority (NDA), the
UgandaNationalCouncilofScienceandTechnology,U.S.FoodandDrugAdministration,theUganda
Ministryof Health,and otheragenciesas partof theirresponsibilitiesfor ensuring theprotection of
researchvolunteers.Representativesofalltheaboveareboundbyrulesofconfidentialitynottoreveal
youridentitytoothers.
Complete confidentiality cannot be promised but every effort will be made to keep the records as
confidentialaspossiblewithinthelimitsofthelaw.Alldataandmedicalinformationobtainedabout
youasanindividualwillbeconsideredimportantandheldinconfidence.
Research and clinical information relating to you will be shared with other investigators and the
scientificcommunitythroughpresentationorpublication;however,youwillnotbeidentifiedbyname
orotherpersonalinformationthatcouldbeusedtoidentifyyou.
Generalclinicaltrial informationwillbekeptin thedatabaseattheNationalMedicalLibraryatthe
NationalInstitutesofHealthonhttp://www.clinicaltrials.gov.Thiswebsitewillnotincludeinformation
thatcanidentifyyou.Atmost,theWebsitewillincludeasummaryoftheresults.
SICKNESSORINJURYASARESULTOFSTUDYPARTICIPATION
Ifyou get sick or injureddue tothevaccination ofthisstudy, you will receiveappropriate medical
treatmentandcareuntilcureorstabilizationasprovidedforbyalimitedfund(setasideforthisstudy)
and a clinical trials medical insurance policy for research-related injuries. While we anticipate the
combination oftheset-asidefundandthe insurancepolicyismorethanenoughtopayforthecosts
associatedwithanystudyrelatedinjuries,thereisalimittotheamountofcoverageavailable.Thestudy
sponsor,MUWRP,andtheU.S.DoDwillnotprovidelong-termmedicalcareforstabilizedresearch-
relatedinjuries.
Thestudyteamisresponsibleforthecostwithoutusinganypersonalhealthcarepackagewhichbelongs
tothevolunteer.MUWRPwillpaycostsuptothelimitfromsetasidefindsorthroughtheinsurance.
However, you will not get any other compensation. You should discuss this thoroughly with the
PrincipalInvestigatororsitecliniciansbeforemakingadecisiontoparticipateinthisstudy.Ifyouhave
anyquestionsaboutstudy-relatedsicknessorinjury,youcancontactthefollowingperson:
Dr.BettyMwesigwa
MakerereUniversityWalterReedProject

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ENDINGSTUDYPARTICIPATION
Youcanchoosenottoparticipateorwithdrawfromthestudyatanytimewithoutanyconsequenceto
you.Althoughyoumaywithdrawfromthestudyatanytime,thesamplesanddatacollecteduptothat
timewillbeusedinaccordancewiththeprotocol.
If you would like to withdraw from this study, please contact the Principal Investigator mentioned
above.Youwillnotloseanylegalrights,includingtherightsformedicaltreatmentandothersifyou
withdrawfromthisstudy.
Although you may be willing to participate in the study, the investigators may not give you the
vaccinationifanyofthefollowingsituationsoccur:
o Studyisstopped.
o Study sponsors, the IRBs, the US FDA or the Uganda NDA request to terminate the
studyforunexpectedreasons.
o Youareunabletocomplywiththestudyrequirements.
o Youarenotwillingtohaveblooddrawnalthoughyouarestillwillingtoparticipatein
otherprocesses.
o Youhaveamedicalproblemwherecontinuingtobeinthestudywouldbeharmfulto
you.
o Otherincidentsoccurredandmaybeharmfultoyouifyoucontinuebeingthestudy
volunteer.
ALTERNATIVES
Thisstudyisnotdesignedtotreatanydiseaseandnoalternativecurrentlyexists.Youmaychoosetonot
participate.
CONFLICTOFINTERESTSTATEMENT
The NIH,including membersof the VRC scientific staff, developedthe experimental Ebolavaccine
beingusedinthisresearchstudy.TheresultsofthisstudycouldplayaroleinwhethertheFDAwill
approvethevaccineforsaleatsometimeinthefuture.Ifapproved,thefuturesaleofthevaccinecould
leadtopaymentstotheNIHandtosomeoftheNIH/VRCscientists.ByUSLaw,governmentscientists
arerequiredtoreceivesuchpaymentfortheirinventions.Otherparticipatinginvestigatorsdonothavea
conflictofinterestasaresultofstudyparticipation.Youwillnotreceivemoneyorothercompensation
should this occur. Please discuss with a study investigator any questions you may haveaboutthese
issues.Thereisnoconflictofinterestwithyourdoctorsatthisresearchsite.
IFYOUNEEDMOREINFORMATIONORHAVEADDITIONALQUESTIONS
Ifyouhaveanyquestionaboutthisstudyorifyouhaveanyproblems,youcancontactthePrincipal
InvestigatorDr.BettyMwesigwaattheresearchclinicon
orbytelephone0
ortollfreeon
orImmaculateNakabuyeon
or


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Ifyouhaveanyquestionandneedtoaskaboutyourrightsoryoudonotgetappropriatetreatmentand
careforsicknessorinjurywhichoccurasadirectresultoftakingpartinthisstudyortheinvestigator
doesnottreatyoufairlyinaccordancewithwhatisdescribedinthisconsentform,youmaymakea
complainttothefollowingbodies:
Forinformationon
Regulatoryquestions
TheExecutiveSecretary,atUgandaNationalCouncilofScienceand
Technology,
oron
Humansubjectprotection
questions
theResearchandEthicsCommittee,Makerere
UniversitySchoolofPublicHealth,MulagoHospitalComplexoro

Pleasekeepacopyofthisdocumentincaseyouwanttoreaditagain.

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STUDYVOLUNTEERSTATEMENT
IhavebeenaskedtotakepartinRV508,“APhaseIOpen-Label,Dose-EscalationClinicalTrialto
EvaluatetheSafety,TolerabilityandImmunogenicityofTwoDosesofanEbolaSudanChimpanzee
AdenovirusVectorVaccine,VRC-EBOADC086-00-VP(cAd3-EBOS),inHealthyAdults”.
TheprincipalinvestigatorDr.BettyMwesigwaorherrepresentativehasexplainedthesignificanceof
thetesting,thedurationofthestudy,thetestingthatIwillundergo,themethodstobeused,andtherisks
anddangersofparticipation.Ihavebeengivenachancetoaskquestionsaboutthisresearchstudy.All
questionswereansweredtomysatisfaction.IfIhaveotherquestionsaboutthisresearch,Icanask:Dr.
Betty Mwesigwa or Immaculate Nakabuye at the research clinic on
or
I am signing below to indicate I wish to take part in this study, and my consent to follow the
requirementsofthestudyasmuchaspossible.Iwilldomybesttofollowtherecommendationsofthe
study team, and I will report all problems occurring from this study to the study team. It has been
explainedtomethatIcanquitthisstudyatanytime,andIwillnotloseanybenefitsnorwillIreceive
anypenalty.IfIdecidetoquitthisstudy,Imaybeexaminedbeforeleavingthestudytoensuremygood
health.ThemedicalcarethatIcouldreceiveasaresultofsicknessfrombeingapartofthisstudyhave
beenexplainedtomeandIhavebeenofferedasignedcopyofthisconsentform.
Iagreetoparticipateinthisstudy.

_________________________________________________
___________
SIGNATUREORMARKOFPARTICIPANT
DATE


_______________________________________________________
PRINTNAMEOFPARTICIPANT


_________________________________________________
___________
SIGNATUREOFPERSONADMINISTERINGCONSENT
DATE


_______________________________________________________
PRINTNAMEOFPERSONADMINISTERINGCONSENT

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INFORMED	CONSENT	FOR	FUTURE	USE	OF	STORED	SPECIMENS	

Study	Title:		RV508,“APhaseIOpen-Label,Dose-EscalationClinicalTrialtoEvaluatetheSafety,
TolerabilityandImmunogenicityofTwoDosesofanEbolaSudanChimpanzee
AdenovirusVectorVaccine,VRC-EBOADC086-00-VP(cAd3-EBOS),inHealthy
Adults”
Sponsor:	NationalInstitutesofHealth(NIH),	NationalInstituteofAllergyandInfectiousDiseases
(NIAID)VaccineResearchCenter(VRC)
Funding	Agencies:	NIH,theU.S.MilitaryHIVResearchProgram(MHRP)andtheU.S.Departmentof
Defense(DoD)
Study	Product	Provided	by:	NIH/NIAID/VRC
Study	Conducted	by:	MakerereUniversityWalterReedProject(MUWRP)
Principal	Investigator:BettyMwesigwa,MBChB,MScClinicalTrials	

Duringthisstudy,youwillbeaskedtoprovideblood.Thesebloodsampleswillbestoredforaslongas
possibleandwillbeusedaccordingtoyourdecisionbelow.Thebloodsampleswillbestoredinthe
UnitedStates(U.S.)fortestinghowyourbodyfightsEbolainfectionandotherfuturestudiesthatwedo
notknowaboutatthistime.Someoftheteststhatmaybeconductedonyourstoredsamplesmaynotbe
developedyet,sotheinvestigatorscannottellyoualltheteststhatmaybeperformedinthefuture.
Thereisachancethatthebloodsamplesyouaredonatingunderthisstudymaybeusedinotherresearch
studiesandmayhavesomecommercialvalue.Yoursampleswillnotbesoldoruseddirectlytoproduce
commercialproducts.
Shouldyourdonatedsample(s)leadtothedevelopmentofacommercialproduct,thestudysponsorand
inventorwillownitandmaytakeactiontopatentandlicensetheproduct.Neitherthesponsornorthe
inventorintendtoprovideyouwithanycompensationforyourbloodsamplesprovidedinthisstudy,nor
foranyfuturevaluethatthesampleyouhavegivenmaybefoundtohave.
Thebloodsampleswillnotbestoredwithanypersonalinformation.Yourstoredsampleswillbelabeled
byacode(suchasanumber)thatonlythestudyteamcanlinktoyou.Allpersonalinformationwillbe
storedbythestudyinvestigatoratthestudysite.Anyidentifyinginformationaboutyouwillbekept
confidentialtotheextentpermittedbylaw.
Youwill notreceive theresults offuture studiesor future genetictests involving your storedblood
samples.Theresultsofgenetictestswillbeforresearchpurposesonly.Thegenetictestsarenotusedin
medicalpracticeandhavenotbeenapprovedforuseinmakinghealthcaredecisions.
Future	Research	on	Your	Samples	Will	Be	Related	to	Ebola	or	Vaccines	
Researchersareabletomeasurehowtheimmunesystemrespondsbylookingatbloodsamples.Wewill
trytounderstandwhyEboladiseaseprogressesdifferentlyinsomepeople.Asnewmethods(orways)
ofmeasuringthebody’simmuneresponsetoEbolaaremadeinthelaboratory,wewouldliketotest
thesemethodsonthesampleswehavealreadycollectedfromyou.Wealsoknowthatsometimesgenes,

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passeddownfromyourparents,canbeimportanttoaperson’simmuneresponsetoEbola.Becauseof
this, we may do genetic testing on your stored samples. We may use methods that have not been
developedyet,sowecannotdescribethemtoyounow.Wewillonlyuseyourstoredsamplestolearn
moreabouthowtheimmunesystemrespondstoEbolaandhowvaccinescanpreventEbolainfection.
Your	Samples	Used	for	Future	Research	Will	Be	Shipped	to	the	USA	
Yoursampleswillbestoredinasecurecentralstoragesite(notintheclinic)intheUSA.Thesamples
willnotbelabeledwithyourname,onlywithyourStudyIdentification(SID)number.Thereisnotime
limitonhowlongyoursampleswillbestored.
Your	Privacy	Will	Be	Protected	
Wewillprotectyourprivacywithanyfutureresearchtestingofyoursamples,justlikewedowithall
researchinformationfromyouduringthemainstudy.Thesampleswillnotbelabeledwithyourname.
Instead,theywillhaveyourstudycode.Afterthisstudyends,whenthesamplesarerequestedforfuture
research,thestudycodestayswiththem,orinsomecases,itisremovedbeforethesamplesaresentto
beused,ifthisinformationisnotnecessaryforthestudy.
An	Institutional	Review	Board/Independent	Ethics	Committee	Will	Review	Any	Future	Research	
on	Your	Samples	
An IRB/Independent Ethics Committee, which is responsible for overseeing the safety, welfare and
rightsofresearchparticipants,mustreviewandapproveeachresearchstudythatintendstouseyour
samplesinfuturestudies.
There	Will	Be	No	Benefit	to	You	If	You	Allow	Us	to	Store	Your	Samples	For	Future	Research	
Theresearcherswillnotcontact you oryourhealthcareproviderwithresultsfromfuturestudiesor
futuregeneticteststhatuseyoursamples.Thisisbecausetheuseofthesamplesisforresearchandthe
testshavenotbeenapprovedforuseinmakinghealthcaredecisions.
Yoursamplesmaycontributetoanewinventionordiscovery.Thereisnoplanforyoutoshareany
moneyorotherbenefitsresultingfromthisinventionordiscovery.
There	Are	Few	Risks	Related	to	Storing	Your	Samples	
Whentestsaredoneonthestoredsamplesthereisasmallbutpossiblerisktoyourprivacy.Itispossible
thatifothersfoundoutinformationaboutyouthatislearnedfromtests(suchasinformationaboutyour
genes)itcouldcauseyouproblemswithyourfamily(e.g.,havingafamilymemberlearnaboutadisease
thatmaybepassedoninfamiliesorlearningwhoisthetrueparentofachild)orproblemsgettingajob
orinsurance.Theriskofthishappeningisextremelylow,becauseyourresultswillnotbeapartofyour
medicalrecordandwillnotbegiventotheclinic.Also,itispossiblethatyourSIDcouldberemoved
fromthesamples.IfyourSIDnumberisremovedfromanysamples,wewillnotbeabletolinkthat
sampletoyou.

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You	Can	Agree	Now	to	Let	Us	Use	Your	Samples	For	Future	Testing	and	Still	Change	Your	Mind	
Later	
Ifyouagreenow,butdecidelaterthatyoudonotwantustouseyoursamplesforfutureresearch,please
tellus.WewillaskthestoragefacilitytodestroyanyremainingsamplesthatstillhaveyourSIDon
themsothattheycannotbeusedforfutureresearch.
For	More	Information:	
Ifyouhavequestionsabouttheuseofyoursamplesforfutureresearch,contactDr.BettyMwesigwaon
Ifyouhaveaproblemthatyouthinkmayberelatedtotheuseofyoursamplesforfutureresearch,orif
youwanttowithdrawyourconsent,contactImmaculateNakabuyeon

Ifyouhavequestionsaboutyourrightsasaresearchparticipant,orproblemsorconcernsabouthowyou
are being treated in this study, you may contact
at the Research and Ethics
Committee, Makerere University School of Public Health, Mulago Hospital Complex o
Onceyouhavereadthisformandhavehadallofyourquestionssatisfactorilyanswered,pleaseinitial
andchecktheboxnexttoyourchoiceofwhetherornotyouconsenttohaveyourbloodsamplesstored
forfuturetesting,andthensigninthespaceprovidedbelow.
_____
initials

Iallowyoutostoreandusemysamplesforfuturetestingwhichmayincludegenetic
testing.
_____
initials

Ido	notallowyoutostoreandusemysamplesforfuturetesting.


_________________________________________________
___________
SIGNATUREORMARKOFPARTICIPANT
DATE


_______________________________________________________
PRINTNAMEOFPARTICIPANT


_________________________________________________
___________
SIGNATUREOFPERSONADMINISTERINGCONSENT
DATE


_______________________________________________________
PRINTNAMEOFPERSONADMINISTERINGCONSENT

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INFORMED	CONSENT	FOR	GENETIC	TESTING	

Study	Title:		RV508,“APhaseIOpen-Label,Dose-EscalationClinicalTrialtoEvaluatetheSafety,
TolerabilityandImmunogenicityofTwoDosesofanEbolaSudanChimpanzee
AdenovirusVectorVaccine,VRC-EBOADC086-00-VP(cAd3-EBOS),inHealthy
Adults”
Sponsor:	NationalInstitutesofHealth(NIH),	NationalInstituteofAllergyandInfectiousDiseases
(NIAID)VaccineResearchCenter(VRC)
Funding	Agencies:	NIH,theU.S.MilitaryHIVResearchProgram(MHRP)andtheU.S.Departmentof
Defense(DoD)
Study	Product	Provided	by:	NIH/NIAID/VRC
Study	Conducted	by:	MakerereUniversityWalterReedProject(MUWRP)
Principal	Investigator:BettyMwesigwa,MBChB,MScClinicalTrials	

Aswetoldyouinthemaininformedconsentformforthisstudyandintheconsentformforstorageof
samplesforfutureuse,wewilldosometestingofyourblood.Someofthetestingthatwewilldowill
begenetictesting.Thisconsentformtellsyoueverythingweknownowaboutgenetictestingusingyour
bloodsamples.
Youcandecidewhetherornottoletususeyourbloodforgenetictests.Yourdecisiondoesnotaffect
yourparticipationinthestudyoranycareyoureceiveatthisclinic.Ifyoudecidetoallowustouseyour
bloodsamplesforgenetictests,wewillaskyoutosignthisform.Youwillgetacopyoftheformto
keep.
Your	Blood	Sample	Is	a	Potential	Source	of	Genetic	Information	
Researchersareabletomeasurehowtheimmunesystemrespondsbylookingatblood.Wewilltryto
understandwhyEbolaandotherdiseasesaffectedbyEbolaprogressdifferentlyinsomepeopleandwhy
somepeoplearemorelikelytobecomeinfectedthanothers.Weknowthatsometimesgenes,passed
downfromyourparents,canbeimportanttoaperson’simmuneresponsetoEbola.Becauseofthis,we
wouldliketodogenetictestingonyourbloodsamples.Wewillonlyperformgenetictestingtolearn
moreabouthowtheimmunesystemrespondstoEbolaandtootherdiseasesaffectedbyEbola.
HLA	and	Genetic	Testing:	Someoftheblooddrawnfromyou,aspartofthisstudywillbeusedfora
testcalledHLAtype.HLAstandsfor‘HumanLeukocyteAntigen’,agroupofproteinspresentonthe
surfaceofallcellsonthehumanbodyandhelpthebody’simmunesystemrespondtoforeign,harmful
substances.Forresearch,HLAtestingisusedtotrytoidentifyfactorsassociatedwithresponsetoa
vaccine,progressionofadiseaseorrelatedconditions.DeterminingHLAtypeisnecessarytobeableto
performcertainresearchstudies.
Wewillnotnotifyyouoftheresultsofanygenetictest.Thegeneticresearchtestsweplantoconduct
arenotcurrentlyusedinmedicalpracticeandhavenotbeenapprovedforuseinmakinghealthcare
decisions.

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Your	Samples	Used	For	Genetic	Testing	Will	Be	Shipped	to	the	USA	
Inordertocompletethegenetictestingonyourbloodsamples,theywillbeshippedandstoredinthe
UnitedStates.Thereisnotimelimitonhowlongyoursampleswillbestored.
Your	Privacy	Will	Be	Protected	
Wewillprotectyourprivacywithanygenetictestingofyourbloodsamples,justlikewedowithall
researchinformationfromyouduringthestudy.Thebloodsampleswillnotbelabeledwithyourname.
Instead,theywillhaveyourstudyidentification(SID)numberonly.Ifyoursamplesaresentoutside
Uganda,theSIDnumberstayswiththem.Yourgenetictestresultswillonlybeconnectedtoyoubythe
SIDnumber,knownonlytothestudyteam,andnotbyyournameorotherpersonalinformation.
There	Will	Be	No	Benefit	to	You	If	You	Allow	Us	to	Use	Your	Samples	For	Genetic	Testing	
Theresearcherswillnotcontactyouoryourhealthcareproviderwithresultsfromthegenetictesting
usingyourblood.Thisisbecausetheuseofthesamplesisforresearchand thetestshavenotbeen
approvedforuseinmakinghealthcaredecisions.
Yoursamplesmaycontributetoanewinventionordiscovery.Thereisnoplanforyoutoshareany
moneyorotherbenefitsresultingfromthisinventionordiscovery.
There	Are	Few	Risks	Related	to	Genetic	Testing	of	Your	Samples	
Risk	of	 genetic	 tests	and	 HLA	testing:	 Thegreatest riskassociated withgenetic testing isto your
privacy.Genetictestresultscanbeusedtoprovideinformationabouthowsusceptibleyouaretocertain
diseases. Used inappropriately, this information could be discriminatory (for example, by insurance
companies).HLAtypingcanalsobeusedtodeterminewhothetrueparentofachildis(ifcomparedto
thechild’sHLAtype).However,theriskofthishappeningisextremelylow,becauseyourresultswill
notbepartofyourmedicalrecordsandwillnotbeprovidedtotheclinic.
Thebloodsamplesthatyouprovidewillonlybeusedtoprovidestudyinvestigatorsinformationabout
yourimmunesystem.Theresultswillbecodedtoprotectyouridentity.YourHLA(andothergenetic
tests)canonlybeconnectedtoyoubythecodedstudynumberandnotbyyournameorotherpersonal
information.Neitheryounoryourdoctorwillbegiventheresultsofthetests.
For	More	Information:	
Ifyouhavequestionsabouttheuseofyoursamplesforgenetictesting,contactDr.BettyMwesigwaon
ortollfreeon
Ifyouhaveaproblemthatyouthinkmayberelatedtotheuseofyoursamplesforgenetictesting,orif
youwanttowithdrawyourconsent,contactImmaculateNakabuyeon
or

Ifyouhavequestionsaboutyourrightsasaresearchparticipant,orproblemsorconcernsabouthowyou
are being treated in this study, you may contact
at the Research and Ethics
Committee, Makerere University School of Public Health, Mulago Hospital Complex or o

RV508/WRAIR#2439

Version1.5
GeneticICF
Page3of3
03March2020
Onceyouhavereadthisformandhavehadallyourquestionssatisfactorilyanswered,pleaseinitialand
checktheboxnexttoyourchoiceofwhetherornotyouconsenttohaveyourbloodsamplesusedfor
genetictesting,andthensigninthespaceprovidedbelow.
_____

Iallowyoutousemysamplesforgenetictesting.
initials
_____

Ido	not	allowyoutodogenetictestingonmysamples.	
initials


_________________________________________________
___________
SIGNATUREORMARKOFPARTICIPANT
DATE


_______________________________________________________
PRINTNAMEOFPARTICIPANT


_________________________________________________
___________
SIGNATUREOFPERSONADMINISTERINGCONSENT
DATE


_______________________________________________________
PRINTNAMEOFPERSONADMINISTERINGCONSENT

RV508/WRAIR#2439

Version1.5
WithdrawSamplesForm
Page1of1
03March2020
WITHDRAWAL	OF	CONSENT	FOR	SAMPLE	STORAGE	

Study	Title:		RV508,“APhaseIOpen-Label,Dose-EscalationClinicalTrialtoEvaluatetheSafety,
TolerabilityandImmunogenicityofTwoDosesofanEbolaSudanChimpanzee
AdenovirusVectorVaccine,VRC-EBOADC086-00-VP(cAd3-EBOS),inHealthy
Adults”
Sponsor:	NationalInstitutesofHealth(NIH),	NationalInstituteofAllergyandInfectiousDiseases
(NIAID)VaccineResearchCenter(VRC)
Funding	Agencies:	NIH,theU.S.MilitaryHIVResearchProgram(MHRP)andtheU.S.Departmentof
Defense(DoD)
Study	Product	Provided	by:	NIH/NIAID/VRC
Study	Conducted	by:	MakerereUniversityWalterReedProject(MUWRP)
Principal	Investigator:BettyMwesigwa,MBChB,MScClinicalTrials	

Volunteer	Statement	of	withdraw	of	consent	to	have	samples	stored	for	future	testing:	
I___________________________________withdrawmyconsenttohavemysamplesstoredforfuture
use.Idonotwanttodonatebloodsamplesforstorageandfutureuse.However,Iwouldstillliketo
continuetakingpartinthemainstudy.IthasbeenexplainedtomethatwhenIsignatthebottomofthis
form,mysampleswillbeusedforallthetestsspecifiedforthispresentstudy,butnobloodwillbe
storedforfutureuse.
Ithasbeenexplainedtomethatwithdrawingmyconsenttohavemysamplesstoredforfutureusewill
notmakeanydifferencetothecareIamreceivingnoworinthefuture,ortoanybenefitsthatIam
entitledto.
IhavebeengivenachancetoaskallthequestionsthatIhaveaboutwithdrawingmyconsenttohavemy
samplesstored.Allofmyquestionswereansweredtomysatisfaction.Iwasofferedasignedcopyof
thisconsent.

_________________________________________________
___________
SIGNATUREORMARKOFPARTICIPANT
DATE


_______________________________________________________
PRINTNAMEOFPARTICIPANT


_________________________________________________
___________
SIGNATUREOFPERSONADMINISTERINGCONSENT
DATE


_______________________________________________________
PRINTNAMEOFPERSONADMINISTERINGCONSENT