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DMID Protocol Template Version 2.028 September 2005

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TITLE

DMID Protocol Number:

DMID Funding Mechanism: (eg, grant #, contract #)

Pharmaceutical Support Provided by: (if applicable)

Other Identifying Numbers:

IND Sponsor: (if applicable. Do not include IND number)

Principal Investigator:

DMID Protocol Champion:

DMID Medical Monitor:

DMID Clinical Affairs Specialist:

DMID Regulatory Affairs Specialist: (if applicable)

Draft or Version Number: (Refer to DMID SOP for assigning version numbers)

Day Month Year(Write out the month and use international date format, eg, 23 January 2004)

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STATEMENT OF COMPLIANCE

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SIGNATURE PAGE

The signature below constitutes the approval of this protocol and the attachments, and provides the necessary assurances that this trial will be conducted according to all stipulations of the protocol, including all statements regarding confidentiality, and according to local legal and regulatory requirements and applicable US federal regulations and ICH guidelines.

Site Investigator:

Signed: Date:NameTitle

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TABLE OF CONTENTS

PageStatement of Compliance...............................................................................................................iiSignature Page..............................................................................................................................iiiTable of Contents..........................................................................................................................ivList of Abbreviations.....................................................................................................................viiProtocol Summary.........................................................................................................................ix1 Key Roles..............................................................................................................................12 Background Information and Scientific Rationale.................................................................2

2.1 Background Information......................................................................................22.2 Rationale.............................................................................................................22.3 Potential Risks and Benefits...............................................................................2

2.3.1 Potential Risks.........................................................................................22.3.2 Known Potential Benefits........................................................................2

3 Objectives.............................................................................................................................33.1 Study Objectives.................................................................................................33.2 Study Outcome Measures...................................................................................3

3.2.1 Primary Outcome Measures....................................................................33.2.2 Secondary Outcome Measures...............................................................3

4 Study Design.........................................................................................................................44.1 Substudies (if applicable)....................................................................................4

5 Study Enrollment and Withdrawal.........................................................................................55.1 Subject Inclusion Criteria.....................................................................................55.2 Subject Exclusion Criteria...................................................................................55.3 Treatment Assignment Procedures.....................................................................5

5.3.1 Randomization Procedures.....................................................................55.3.2 Masking Procedures................................................................................55.3.3 Reasons for Withdrawal..........................................................................55.3.4 Handling of Withdrawals..........................................................................55.3.5 Termination of Study...............................................................................5

6 Study Intervention/Investigational Product............................................................................66.1 Study Product Description...................................................................................6

6.1.1 Acquisition...............................................................................................66.1.2 Formulation, Packaging, and Labeling....................................................66.1.3 Product Storage and Stability..................................................................6

6.2 Dosage, Preparation and Administration of Study Intervention/Investigational Product................................................................................................................6

6.3 Modification of Study Intervention/Investigational Product for a Participant.......66.4 Accountability Procedures for the Study Intervention/Investigational Product(s)66.5 Assessment of Subject Compliance with Study Intervention/Investigational

Product................................................................................................................6______________________________________________________________________________________________

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6.6 Concomitant Medications/Treatments.................................................................77 Study Schedule.....................................................................................................................8

7.1 Screening............................................................................................................87.2 Enrollment/Baseline............................................................................................87.3 Follow-up.............................................................................................................87.4 Final Study Visit...................................................................................................87.5 Early Termination Visit........................................................................................87.6 Unscheduled Visit................................................................................................8

8 Study Procedures/Evaluations..............................................................................................98.1 Clinical Evaluations.............................................................................................98.2 Laboratory Evaluations........................................................................................9

8.2.1 Clinical Laboratory Evaluations...............................................................98.2.2 Special Assays or Procedures................................................................98.2.3 Specimen Preparation, Handling, and Shipping......................................9

9 Assessment of Safety.........................................................................................................109.1 Specification of Safety Parameters...................................................................109.2 Methods and Timing for Assessing, Recording, and Analyzing Safety

Parameters........................................................................................................109.2.1 Adverse Events.....................................................................................109.2.2 Reactogenicity (for Vaccine Studies and Some Therapeutic Trials).....109.2.3 Serious Adverse Events........................................................................109.2.4 Procedures to be Followed in the Event of Abnormal Laboratory Test

Values or Abnormal Clinical Findings....................................................109.3 Reporting Procedures.......................................................................................10

9.3.1 Regulatory Reporting for Studies Conducted Under DMID-Sponsored IND........................................................................................................10

9.3.2 Regulatory Reporting for Studies Not Conducted Under DMID-Sponsored IND............................................................................10

9.3.3 Other Adverse Events (if applicable).....................................................119.3.4 Reporting of Pregnancy.........................................................................11

9.4 Type and Duration of Follow-up of Subjects after Adverse Events...................119.5 Halting Rules.....................................................................................................119.6 Safety Oversight (ISM plus SMC or DSMB)......................................................11

10 Clinical Monitoring...............................................................................................................1210.1 Site Monitoring Plan..........................................................................................12

11 Statistical Considerations....................................................................................................1311.1 Study Hypotheses.............................................................................................1311.2 Sample Size Considerations.............................................................................1311.3 Planned Interim Analyses (if applicable)...........................................................13

11.3.1 Safety Review........................................................................................1311.3.2 Immunogenicity or Efficacy Review.......................................................13

11.4 Final Analysis Plan............................................................................................13

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12 Source Documents and Access to Source Data/Documents.............................................1413 Quality Control and Quality Assurance...............................................................................1514 Ethics/Protection of Human Subjects..................................................................................16

14.1 Ethical Standard................................................................................................1614.2 Institutional Review Board.................................................................................1614.3 Informed Consent Process................................................................................16

14.3.1 Informed Consent/Assent Process (in Case of a Minor).......................1614.4 Exclusion of Women, Minorities, and Children (Special Populations)...............1614.5 Subject Confidentiality.......................................................................................1614.6 Study Discontinuation.......................................................................................1614.7 Future Use of Stored Specimens......................................................................16

15 Data Handling and Record Keeping...................................................................................1715.1 Data Management Responsibilities...................................................................1715.2 Data Capture Methods......................................................................................1715.3 Types of Data....................................................................................................1715.4 Timing/Reports..................................................................................................1715.5 Study Records Retention..................................................................................1715.6 Protocol Deviations...........................................................................................17

16 Publication Policy................................................................................................................1817 Literature References.........................................................................................................19Supplements/Appendices............................................................................................................20Appendix A: Schedule of Events.................................................................................................21

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LIST OF ABBREVIATIONS

AE Adverse Event/Adverse ExperienceCFR Code of Federal RegulationsCIOMS Council for International Organizations of Medical SciencesCONSORT Consolidated Standards of Reporting TrialsCFR Code of Federal RegulationsCRF Case Report FormCRO Contract Research OrganizationDCC Data Coordinating CenterDHHS Department of Health and Human ServicesDMID Division of Microbiology and Infectious Diseases, NIAID, NIH,

DHHSDSMB Data and Safety Monitoring BoardeCRF Electronic Case Report FormFDA Food and Drug AdministrationFWA Federalwide AssuranceGCP Good Clinical PracticeHIPAA Health Insurance Portability and Accountability ActIB Investigator’s BrochureICF Informed Consent FormICH International Conference on HarmonisationICMJE International Committee of Medical Journal EditorsIDE Investigational Device ExemptionIEC Independent or Institutional Ethics CommitteeIND Investigational New Drug ApplicationIRB Institutional Review BoardISM Independent Safety MonitorJAMA Journal of the American Medical AssociationMedDRA Medical Dictionary for Regulatory ActivitiesMOP Manual of ProceduresN Number (typically refers to subjects)NCI National Cancer Institute, NIH, DHHSNDA New Drug ApplicationNEJM New England Journal of MedicineNIAID National Institute of Allergy and Infectious Diseases, NIH, DHHSNIH National Institutes of HealthOCRA Office of Clinical Research Affairs, DMID, NIAID, NIH, DHHSOHRP Office for Human Research ProtectionsOHSR Office for Human Subjects ResearchORA Office of Regulatory Affairs, DMID, NIAID, NIH, DHHSPHI Protected Health Information

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PI Principal InvestigatorPK PharmacokineticsQA Quality AssuranceQC Quality ControlSAE Serious Adverse Event/Serious Adverse ExperienceSMC Safety Monitoring CommitteeSOP Standard Operating ProcedureUS United StatesWHO World Health Organization

Please modify list to include your protocol-specific terms.

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PROTOCOL SUMMARY

Title:

Phase:

Population:

Number of Sites:

Study Duration:

Subject Participation Duration:

Description of Agent or Intervention:

Objectives: Primary:

Secondary:

Description of Study Design:

Estimated Time to Complete Enrollment:

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Schematic of Study Design:

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1 KEY ROLES

Individuals:

Protocol Champion:

Principal Investigator:

Medical Monitor: (if applicable)

Institutions:

Optional:

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2 BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE

2.1 Background Information

2.2 Rationale

2.3 Potential Risks and Benefits

2.3.1 Potential Risks

2.3.2 Known Potential Benefits

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3 OBJECTIVES

3.1 Study Objectives

3.2 Study Outcome Measures

3.2.1 Primary Outcome Measures

3.2.2 Secondary Outcome Measures

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4 STUDY DESIGN

4.1 Substudies (if applicable)

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5 STUDY ENROLLMENT AND WITHDRAWAL

5.1 Subject Inclusion Criteria

5.2 Subject Exclusion Criteria

5.3 Treatment Assignment Procedures

5.3.1 Randomization Procedures

5.3.2 Masking Procedures

5.3.3 Reasons for Withdrawal

5.3.4 Handling of Withdrawals

5.3.5 Termination of Study

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6 STUDY INTERVENTION/INVESTIGATIONAL PRODUCT

6.1 Study Product Description

6.1.1 Acquisition

6.1.2 Formulation, Packaging, and Labeling

6.1.3 Product Storage and Stability

6.2 Dosage, Preparation and Administration of Study Intervention/Investigational Product

6.3 Modification of Study Intervention/Investigational Product for a Participant

6.4 Accountability Procedures for the Study Intervention/Investigational Product(s)

6.5 Assessment of Subject Compliance with Study Intervention/Investigational Product

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6.6 Concomitant Medications/Treatments

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7 STUDY SCHEDULE

7.1 Screening

7.2 Enrollment/Baseline

7.3 Follow-up

7.4 Final Study Visit

7.5 Early Termination Visit

7.6 Unscheduled Visit

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8 STUDY PROCEDURES/EVALUATIONS

8.1 Clinical Evaluations

8.2 Laboratory Evaluations

8.2.1 Clinical Laboratory Evaluations

8.2.2 Special Assays or Procedures

8.2.3 Specimen Preparation, Handling, and Shipping

8.2.3.1 Instructions for Specimen Preparation, Handling, and Storage

8.2.3.2 Specimen Shipment

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9 ASSESSMENT OF SAFETY

9.1 Specification of Safety Parameters

9.2 Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters

9.2.1 Adverse Events

9.2.2 Reactogenicity (for Vaccine Studies and Some Therapeutic Trials)

9.2.3 Serious Adverse Events

9.2.4 Procedures to be Followed in the Event of Abnormal Laboratory Test Values or Abnormal Clinical Findings

9.3 Reporting Procedures

9.3.1 Regulatory Reporting for Studies Conducted Under DMID-Sponsored IND

9.3.2 Regulatory Reporting for Studies Not Conducted Under DMID-Sponsored IND

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9.3.3 Other Adverse Events (if applicable)

9.3.4 Reporting of Pregnancy

9.4 Type and Duration of Follow-up of Subjects after Adverse Events

9.5 Halting Rules

9.6 Safety Oversight (ISM plus SMC or DSMB)

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10 CLINICAL MONITORING

10.1 Site Monitoring Plan

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11 STATISTICAL CONSIDERATIONS

11.1 Study Hypotheses

11.2 Sample Size Considerations

11.3 Planned Interim Analyses (if applicable)

11.3.1 Safety Review

11.3.2 Immunogenicity or Efficacy Review

11.4 Final Analysis Plan

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12 SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS

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13 QUALITY CONTROL AND QUALITY ASSURANCE

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14 ETHICS/PROTECTION OF HUMAN SUBJECTS

14.1 Ethical Standard

14.2 Institutional Review Board

14.3 Informed Consent Process

14.3.1 Informed Consent/Assent Process (in Case of a Minor)

14.4 Exclusion of Women, Minorities, and Children (Special Populations)

14.5 Subject Confidentiality

14.6 Study Discontinuation

14.7 Future Use of Stored Specimens

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15 DATA HANDLING AND RECORD KEEPING

15.1 Data Management Responsibilities

15.2 Data Capture Methods

15.3 Types of Data

15.4 Timing/Reports

15.5 Study Records Retention

15.6 Protocol Deviations

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16 PUBLICATION POLICY

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17 LITERATURE REFERENCES

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SUPPLEMENTS/APPENDICES

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APPENDIX A: SCHEDULE OF EVENTS

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