裂谷热核心方案

CORE Protocol Simple,large-scale, multi-country individuallyrandomized placebo-controlled trial A phase 2/3 study to evaluate the safety, tolerability, immunogenicity, andefficacy of vaccinecandidates against Rift Valley Fever (RVF) disease inhealthy individuals at risk of RVF disease. Document Version:CORE Protocol v1.0Date Prepared:[DATE]Status:For Discussion and Development 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 requirecoordination across multiple stakeholder organizations, regulatory approvals,and further development of vaccine-specific and site-specific operationalprocedures. TABLE OF CONTENTS 1.GENERAL INFORMATION5 1.1SPONSOR ANDCO-SPONSORS51.2TRIALINVESTIGATORINFORMATION51.3TRIALINVESTIGATORINFORMATION51.4STUDYSYPNOSIS6 STATEMENT OF COMPLIANCE9 ABBREVIATIONS10 2. BACKGROUND INFORMATION11 2.1EPIDEMIOLOGY OFRVF11 2.1.1GLOBALDISTRIBUTION112.1.2HUMANDISEASEBURDEN112.1.3HIGH-RISKPOPULATIONS112.1.4EPIDEMIOLOGY OFRVFINEACHCOUNTRY12 2.2CLINICALPRESENTATION122.3NEED FOR ASTUDY OF THESAFETY,IMMUNOGENICITY,ANDEFFICACY OFVACCINATION12 3. INVESTIGATIONAL PRODUCTS13 3.2COMPARATOR13PLACEBO ORACTIVECOMPARATOR:13 4.TRIAL OBJECTIVES AND PURPOSE14 4.1PHASE2OBJECTIVES:DURINGINTER-EPIDEMIC ANDOUTBREAKPERIODS4.1.1PRIMARYO BJECTIVES144.1.2SECONDARYOBJECTIVES154.1.3EXPLORATORYOBJECTIVES15 4.2.1PRIMARYOBJECTIVE164.2.2SECONDARYOBJECTIVES164.2.3EXPLORATORYOBJECTIVES17 5. ASSESSMENT OF EFFICACY21 5.1DEFINITION OFSUSPECTEDRVFDISEASE215.2ADDITIONALWHOSURVEILLANCE DEFINITION FOR EARLY DISEASE215.3DEFINITION OFPROBABLERVFDISEASE215.4DEFINITION OFCONFIRMEDRVFDISEASE225.5ADDITIONALCLINICALCONSIDERATIONS225.6DISCARDEDCASE22 6.STUDY POPULATION23 6.1TARGETPOPULATION236.1.1GEOGRAPHICTARGET236.1.2DEMOGRAPHICTARGET236.1.3OCCUPATIONAL/RISKTARGET236.2POPULATIONJUSTIFICATION236.3INCLUSIONCRITERIA236.4EXCLUSIONCRITERIA23 7.1TRIAL-WIDEDURATION24 7.1.1PHASE2ENROLLMENTPERIOD247.1.2PHASE3ENROLLMENTPERIOD247.1.3OVERALLTRIALDURATION:24 8.STUDY PROCEDURES25 8.1DURING THEINTER-EPIDEMICPERIOD258.2DURINGOUTBREAKS25ADVERSEEVENTMONITORINGSCHEDULE-DRAFT28ADVERSEEVENTASSESSMENT28 8.3TREATMENT AND INTERVENTIONS28 9.1SAMPLESIZE299.1.1SAMPLESIZEJUSTIFICATION299.2BIASMINIMIZATIONMEASURES299.2.1RANDOMIZATION ANDALLOCATIONCONCEALMENT299.2.2BLINDINGPROCEDURES299.2.3OUTCOMEASSESSMENTBLINDING299.3STATISTICALANALYSIS309.3.1INTERIMEFFICACYTARGET309.3.2FINALPOWER309.3.3PRIMARYANALYSIS309.3.4SECONDARYANALYSES309.4INTERIMANALYSISPLAN319.5STOPPING RULES31 10.1ETHICSAPPROVAL3210.2APPROVAL BYNATIONALREGULATORYAUTHORITIES3210.3PRIVACY ANDCONFIDENTIALITY OFPARTICIPANTS3210.4DECISION BY A VOLUNTEER OR LEGAL REPRESENTATIVE TO WITHDRAW FROM FOLLOW-UP32 11. DISCONTINUATION AND WITHDRAWAL33 11.1DISCONTINUATION FROMINVESTIGATIONALPRODUCT33CRITERIA FORDISCONTINUINGVACCINE33 11.2WITHDRAWAL FROMTRIAL33CRITERIA FORTRIALWITHDRAWAL3311.3PARTICIPANTREPLACEMENT34 12. COMMUNITY ENGAGEMENT35 13. ADMINISTRATIVE ASPECTS36 13.1REGISTRATION OF THESTUDY3613.2AMENDMENTS TO THEPROTOCOL3613.2.1SUBSTANTIALAMENDMENTS3613.2.2NON-SUBSTANTIALADMINISTRATIVECHANGES3613.3FINANCING3613.4INSURANCE36 14. STUDY ORGANIZATION37 14.1TRIALGOVERNANCEFRAMEWORK3714.2TRIALCO-SPONSORS3714.3VACCINEDEVELOPERS3714.2TRIALSCIENTIFICCOMMITTEE(TSC)3714.3DATASAFETYMONITORINGBOARD(DSMB)37 15. DATA MANAGEMENT AND RETENTION OF RECORDS39 15.1DATAOVERSIGHT3915.2TRIALMASTERFILE ANDINVESTIGATORSITEFILE39RECORD-KEEPING3915.3DATAMANAGEMENT3915.4SOURCERECORDS ANDSTUDYRECORDRETENTION39 16. QUALITY ASSURANCE AND CONTROL40 16.1TRAINING TOENSURETRIALQUALITY4016.2MONITORINGPROTOCOLCOMPLIANCE4016.3PROTOCOLDEVIATIONS ANDVIOLATIONS40 16.4INSPECTIONS 17.1PUBLICATIONPOLICY4141 17.1.1O WNERSHIP17.1.2AUTHORSHIP4117.1.3PUBLICATIONTIMING4117.1.4REVIEWPROCESS4117.1.5TRANSPARENCY4117.2DATASHARING4117.2.1DE-IDENTIFICATION4117.2.2DATASHARINGAGREEMENTS41 REFERENCES42 ANNEXES ANNEX1:STANDARDOPERATINGPROCEDURES ANDELECTRONICCASERECORDFORMS43ANNEX2:HISTORY OFPROTOCOLAMENDMENTS43ANNEX3:TRIALGOVERNANCEFRAMEWORK43 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 Conferenceon Harmonisation Good Clinical Practice (ICH GCP) Guideline E6(R3)oThe Declaration of Helsinki and its amendments oApplicable 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,and the relevant Ethics Committee(s), and the National Drug Authority andapproved. Approval of both the protocol and the consent form must be obtained beforeany participant is enrolled. No participantenrolmentwi