裂谷热核心方案

CORE Protocol Simple,large-scale, multi-country individually A phase 2/3 study to evaluate the safety, tolerability, immunogenicity, andefficacy of vaccinecandidates against Rift Valley Fever (RVF) disease in Document Version:CORE Protocol v1.0Date Prepared:[DATE] This protocol is a comprehensiveframework document incorporating thestructural design elements of the WHO CORE Protocol, adapted to the specificcontext of Rift Valley Fever vaccine trials. Implementation will require TABLE OF CONTENTS 1.GENERAL INFORMATION 1.1SPONSOR ANDCO-SPONSORS1.2TRIALINVESTIGATORINFORMATION1.3TRIALINVESTIGATORINFORMATION1.4STUDYSYPNOSIS STATEMENT OF COMPLIANCE ABBREVIATIONS10 2. BACKGROUND INFORMATION 2.1EPIDEMIOLOGY OFRVF2.1.1GLOBALDISTRIBUTION2.1.2HUMANDISEASEBURDEN2.1.3HIGH-RISKPOPULATIONS2.1.4EPIDEMIOLOGY OFRVFINEACHCOUNTRY 2.2CLINICALPRESENTATION2.3NEED FOR ASTUDY OF THESAFETY,IMMUNOGENICITY,ANDEFFICACY OFVACCINATION 3. INVESTIGATIONAL PRODUCTS 3.1VACCINECANDIDATES13VACCINECANDIDATE1:13VACCINECANDIDATES2,3(IF APPLICABLE):133.2COMPARATOR13PLACEBO ORACTIVECOMPARATOR:13 4.TRIAL OBJECTIVES AND PURPOSE 4.1PHASE2OBJECTIVES:DURINGINTER-EPIDEMIC ANDOUTBREAKP4.1.1PRIMARYOBJECTIVES4.1.2SECONDARYOBJECTIVES4.1.3EXPLORATORYOBJECTIVES ERIODS 1414 1616 4.2PHASE3OBJECTIVES:DURINGOUTBREAKS4.2.1PRIMARYOBJECTIVE4.2.2SECONDARYOBJECTIVES4.2.3EXPLORATORYOBJECTIVES 5. ASSESSMENT OF EFFICACY 5.1DEFINITION OFSUSPECTEDRVFDISEASE5.2ADDITIONALWHOSURVEILLANCE DEFINITION FOR EARLY DISEASE5.3DEFINITION OFPROBABLERVFDISEASE5.4DEFINITION OFCONFIRMEDRVFDISEASE5.5ADDITIONALCLINICALCONSIDERATIONS5.6DISCARDEDCASE 6.STUDY POPULATION23 23 6.1TARGETPOPULATION6.1.1GEOGRAPHICTARGET6.1.2DEMOGRAPHICTARGET6.1.3OCCUPATIONAL/RISKTARGET6.2POPULATIONJUSTIFICATION6.3INCLUSIONCRITERIA6.4EXCLUSIONCRITERIA 7.STUDY VISITS 7.1TRIAL-WIDEDURATION7.1.1PHASE2ENROLLMENTPERIOD7.1.2PHASE3ENROLLMENTPERIOD7.1.3OVERALLTRIALDURATION: 8.STUDY PROCEDURES 8.1DURING THEINTER-EPIDEMICPERIOD8.2DURINGOUTBREAKSADVERSEEVENTMONITORINGSCHEDULE-DRAFTADVERSEEVENTASSESSMENT 8.3TREATMENT AND INTERVENTIONS 9.STATISTICS 29 9.1SAMPLESIZE9.1.1SAMPLESIZEJUSTIFICATION9.2BIASMINIMIZATIONMEASURES9.2.1RANDOMIZATION ANDALLOCATIONCONCEALMENT9.2.2BLINDINGPROCEDURES9.2.3OUTCOMEASSESSMENTBLINDING9.3STATISTICALANALYSIS9.3.1INTERIMEFFICACYTARGET9.3.2FINALPOWER9.3.3PRIMARYANALYSIS9.3.4SECONDARYANALYSES9.4INTERIMANALYSISPLAN9.5STOPPING RULES 10.ETHICAL AND REGULATORY ASPECTS 10.1ETHICSAPPROVAL10.2APPROVAL BYNATIONALREGULATORYAUTHORITIES10.3PRIVACY ANDCONFIDENTIALITY OFPARTICIPANTS10.4DECISION BY A VOLUNTEER OR LEGAL REPRESENTATIVE TO WITHDRAW FROM FOLLOW- 11. DISCONTINUATION AND WITHDRAWAL 11.1DISCONTINUATION FROMINVESTIGATIONALPCRITERIA FORDISCONTINUINGVACCINE11.2WITHDRAWAL FROMTRIALCRITERIA FORTRIALWITHDRAWAL11.3PARTICIPANTREPLACEMENT 12. COMMUNITY ENGAGEMENT 13. ADMINISTRATIVE ASPECTS 13.1REGISTRATION OF THESTUDY13.2AMENDMENTS TO THEPROTOCOL13.2.1SUBSTANTIALAMENDMENTS13.2.2NON-SUBSTANTIALADMINISTRATIVEC13.3FINANCING13.4INSURANCE 14. STUDY ORGANIZATION 14.1TRIALGOVERNANCEFRAMEWORK14.2TRIALCO-SPONSORS14.3VACCINEDEVELOPERS14.2TRIALSCIENTIFICCOMMITTEE(TSC)14.3DATASAFETYMONITORINGBOARD(DSMB) 15. DATA MANAGEMENT AND RETENTION OF RECORDS 15.1DATAOVERSIGHT15.2TRIALMASTERFILE ANDINVESTIGATORSITEFILERECORD-KEEPING15.3DATAMANAGEMENT15.4SOURCERECORDS ANDSTUDYRECORDRETENTION 16. QUALITY ASSURANCE AND CONTROL 16.1TRAINING TOENSURETRIALQUALITY16.2MONITORINGPROTOCOLCOMPLIANCE16.3PROTOCOLDEVIATIONS ANDVIOLATIONS 16.4INSPECTIONS 17. DATA SHARING AND PUBLICATIONS 17.1PUBLICATIONPOLICY17.1.1OWNERSHIP17.1.2AUTHORSHIP17.1.3PUBLICATIONTIMING17.1.4REVIEWPROCESS17.1.5TRANSPARENCY17.2DATASHARING17.2.1DE-IDENTIFICATION REFERENCES ANNEXES ANNEX1:STANDARDOPERATINGPROCEDURES ANDELECTRONICCASERECORDFORMSANNEX2:HISTORY OFPROTOCOLAMENDMENTSANNEX3:TRIALGOVERNANCEFRAMEWORK 1.GENERAL INFORMATION 1.1Sponsor and Co-Sponsors 1.2TrialInvestigator Information 1.4StudySynopsis STATEMENT OF COMPLIANCE The study will be carried out in accordance withthe International Conference oThe Declaration of Helsinki and its amendmentsoApplicable national and international regulatory requirementsoUNESCO Universal Declaration on Bioethics and Human RightsoWHO Guidelines on Good Participatory Practices The protocol, informed consent form(s), recruitment materials, and allparticipant materials will be submitted to the WHO Ethical Review Committee, Approval of both the protocol and the consent form must be obtained before No participantenrolmentwill commence until written approval is obtainedfrom all required ethics committees and regulatory authorities. Any amendment to the protocol will require review and approval by therelevantEthics Committee(s)and National Drug Authoritybefore the changes ABBREVIATIONS AbbreviationDefinitionAEAdverse eventCEPICoalition for Epidemic Preparedness InnovationsCIConfidence IntervalCRFCase Report FormDSMBData Safety Monitoring BoardeCRFElectronic case record formELISAEnzyme Li