**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)*

[]{#__RefHeading___Toc114558131 .anchor}Statement of Compliance

[]{#__RefHeading___Toc114558132 .anchor}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 |                                         |     |              |
| I    |                                         |     |              |
| nves |                                         |     |              |
| tiga |                                         |     |              |
| tor: |                                         |     |              |
+------+-----------------------------------------+-----+--------------+
| Sig  |                                         | Da  |              |
| ned: |                                         | te: |              |
+------+-----------------------------------------+-----+--------------+
|      | Name                                    |     |              |
|      |                                         |     |              |
|      | Title                                   |     |              |
+------+-----------------------------------------+-----+--------------+

[]{#__RefHeading___Toc114558133 .anchor}Table of Contents

Page

[Statement of Compliance ii](#__RefHeading___Toc114558131)

[Signature Page iii](#__RefHeading___Toc114558132)

[Table of Contents iv](#__RefHeading___Toc114558133)

[List of Abbreviations vii](#__RefHeading___Toc114558134)

[Protocol Summary ix](#__RefHeading___Toc114558135)

[1 Key Roles 1](#key-roles)

[2 Background Information and Scientific Rationale
2](#background-information-and-scientific-rationale)

[2.1 Background Information 2](#background-information)

[2.2 Rationale 2](#rationale)

[2.3 Potential Risks and Benefits 2](#potential-risks-and-benefits)

[2.3.1 Potential Risks 2](#potential-risks)

[2.3.2 Known Potential Benefits 2](#known-potential-benefits)

[3 Objectives 3](#objectives)

[3.1 Study Objectives 3](#study-objectives)

[3.2 Study Outcome Measures 3](#study-outcome-measures)

[3.2.1 Primary Outcome Measures 3](#primary-outcome-measures)

[3.2.2 Secondary Outcome Measures 3](#secondary-outcome-measures)

[4 Study Design 4](#study-design)

[4.1 Substudies (if applicable) 4](#substudies-if-applicable)

[5 Study Enrollment and Withdrawal 5](#study-enrollment-and-withdrawal)

[5.1 Subject Inclusion Criteria 5](#subject-inclusion-criteria)

[5.2 Subject Exclusion Criteria 5](#subject-exclusion-criteria)

[5.3 Treatment Assignment Procedures
5](#treatment-assignment-procedures)

[5.3.1 Randomization Procedures 5](#randomization-procedures)

[5.3.2 Masking Procedures 5](#masking-procedures)

[5.3.3 Reasons for Withdrawal 5](#reasons-for-withdrawal)

[5.3.4 Handling of Withdrawals 5](#handling-of-withdrawals)

[5.3.5 Termination of Study 5](#termination-of-study)

[6 Study Intervention/Investigational Product
6](#study-interventioninvestigational-product)

[6.1 Study Product Description 6](#study-product-description)

[6.1.1 Acquisition 6](#acquisition)

[6.1.2 Formulation, Packaging, and Labeling
6](#formulation-packaging-and-labeling)

[6.1.3 Product Storage and Stability 6](#product-storage-and-stability)

[6.2 Dosage, Preparation and Administration of Study
Intervention/Investigational Product
6](#dosage-preparation-and-administration-of-study-interventioninvestigational-product)

[6.3 Modification of Study Intervention/Investigational Product for a
Participant
6](#modification-of-study-interventioninvestigational-product-for-a-participant)

[6.4 Accountability Procedures for the Study
Intervention/Investigational Product(s)
6](#accountability-procedures-for-the-study-interventioninvestigational-products)

[6.5 Assessment of Subject Compliance with Study
Intervention/Investigational Product
6](#assessment-of-subject-compliance-with-study-interventioninvestigational-product)

[6.6 Concomitant Medications/Treatments
7](#concomitant-medicationstreatments)

[7 Study Schedule 8](#study-schedule)

[7.1 Screening 8](#screening)

[7.2 Enrollment/Baseline 8](#enrollmentbaseline)

[7.3 Follow-up 8](#follow-up)

[7.4 Final Study Visit 8](#final-study-visit)

[7.5 Early Termination Visit 8](#early-termination-visit)

[7.6 Unscheduled Visit 8](#unscheduled-visit)

[8 Study Procedures/Evaluations 9](#study-proceduresevaluations)

[8.1 Clinical Evaluations 9](#clinical-evaluations)

[8.2 Laboratory Evaluations 9](#laboratory-evaluations)

[8.2.1 Clinical Laboratory Evaluations
9](#clinical-laboratory-evaluations)

[8.2.2 Special Assays or Procedures 9](#special-assays-or-procedures)

[8.2.3 Specimen Preparation, Handling, and Shipping
9](#specimen-preparation-handling-and-shipping)

[9 Assessment of Safety 10](#assessment-of-safety)

[9.1 Specification of Safety Parameters
10](#specification-of-safety-parameters)

[9.2 Methods and Timing for Assessing, Recording, and Analyzing Safety
Parameters
10](#methods-and-timing-for-assessing-recording-and-analyzing-safety-parameters)

[9.2.1 Adverse Events 10](#adverse-events)

[9.2.2 Reactogenicity (for Vaccine Studies and Some Therapeutic Trials)
10](#reactogenicity-for-vaccine-studies-and-some-therapeutic-trials)

[9.2.3 Serious Adverse Events 10](#serious-adverse-events)

[9.2.4 Procedures to be Followed in the Event of Abnormal Laboratory
Test Values or Abnormal Clinical Findings
10](#procedures-to-be-followed-in-the-event-of-abnormal-laboratory-test-values-or-abnormal-clinical-findings)

[9.3 Reporting Procedures 10](#reporting-procedures)

[9.3.1 Regulatory Reporting for Studies Conducted Under DMID‑Sponsored
IND
10](#regulatory-reporting-for-studies-conducted-under-dmidsponsored-ind)

[9.3.2 Regulatory Reporting for Studies Not Conducted Under
DMID‑Sponsored IND
10](#regulatory-reporting-for-studies-not-conducted-under-dmidsponsored-ind)

[9.3.3 Other Adverse Events (if applicable)
11](#other-adverse-events-if-applicable)

[9.3.4 Reporting of Pregnancy 11](#reporting-of-pregnancy)

[9.4 Type and Duration of Follow-up of Subjects after Adverse Events
11](#type-and-duration-of-follow-up-of-subjects-after-adverse-events)

[9.5 Halting Rules 11](#halting-rules)

[9.6 Safety Oversight (ISM plus SMC or DSMB)
11](#safety-oversight-ism-plus-smc-or-dsmb)

[10 Clinical Monitoring 12](#clinical-monitoring)

[10.1 Site Monitoring Plan 12](#site-monitoring-plan)

[11 Statistical Considerations 13](#statistical-considerations)

[11.1 Study Hypotheses 13](#study-hypotheses)

[11.2 Sample Size Considerations 13](#sample-size-considerations)

[11.3 Planned Interim Analyses (if applicable)
13](#planned-interim-analyses-if-applicable)

[11.3.1 Safety Review 13](#safety-review)

[11.3.2 Immunogenicity or Efficacy Review
13](#immunogenicity-or-efficacy-review)

[11.4 Final Analysis Plan 13](#final-analysis-plan)

[12 Source Documents and Access to Source Data/Documents
14](#source-documents-and-access-to-source-datadocuments)

[13 Quality Control and Quality Assurance
15](#quality-control-and-quality-assurance)

[14 Ethics/Protection of Human Subjects
16](#ethicsprotection-of-human-subjects)

[14.1 Ethical Standard 16](#ethical-standard)

[14.2 Institutional Review Board 16](#institutional-review-board)

[14.3 Informed Consent Process 16](#informed-consent-process)

[14.3.1 Informed Consent/Assent Process (in Case of a Minor)
16](#informed-consentassent-process-in-case-of-a-minor)

[14.4 Exclusion of Women, Minorities, and Children (Special Populations)
16](#exclusion-of-women-minorities-and-children-special-populations)

[14.5 Subject Confidentiality 16](#subject-confidentiality)

[14.6 Study Discontinuation 16](#study-discontinuation)

[14.7 Future Use of Stored Specimens
16](#future-use-of-stored-specimens)

[15 Data Handling and Record Keeping
17](#data-handling-and-record-keeping)

[15.1 Data Management Responsibilities
17](#data-management-responsibilities)

[15.2 Data Capture Methods 17](#data-capture-methods)

[15.3 Types of Data 17](#types-of-data)

[15.4 Timing/Reports 17](#timingreports)

[15.5 Study Records Retention 17](#study-records-retention)

[15.6 Protocol Deviations 17](#protocol-deviations)

[16 Publication Policy 18](#publication-policy)

[17 Literature References 19](#literature-references)

[Supplements/Appendices 20](#__RefHeading___Toc114558226)

[Appendix A: Schedule of Events 21](#__RefHeading___Toc114558227)

[]{#__RefHeading___Toc114558134 .anchor}List of Abbreviations

  ---------------------- ------------------------------------------------
  AE                     Adverse Event/Adverse Experience

  CFR                    Code of Federal Regulations

  CIOMS                  Council for International Organizations of
                         Medical Sciences

  CONSORT                Consolidated Standards of Reporting Trials

  CFR                    Code of Federal Regulations

  CRF                    Case Report Form

  CRO                    Contract Research Organization

  DCC                    Data Coordinating Center

  DHHS                   Department of Health and Human Services

  DMID                   Division of Microbiology and Infectious
                         Diseases, NIAID, NIH, DHHS

  DSMB                   Data and Safety Monitoring Board

  eCRF                   Electronic Case Report Form

  FDA                    Food and Drug Administration

  FWA                    Federalwide Assurance

  GCP                    Good Clinical Practice

  HIPAA                  Health Insurance Portability and Accountability
                         Act

  IB                     Investigator's Brochure

  ICF                    Informed Consent Form

  ICH                    International Conference on Harmonisation

  ICMJE                  International Committee of Medical Journal
                         Editors

  IDE                    Investigational Device Exemption

  IEC                    Independent or Institutional Ethics Committee

  IND                    Investigational New Drug Application

  IRB                    Institutional Review Board

  ISM                    Independent Safety Monitor

  JAMA                   Journal of the American Medical Association

  MedDRA ^^             Medical Dictionary for Regulatory Activities

  MOP                    Manual of Procedures

  N                      Number (typically refers to subjects)

  NCI                    National Cancer Institute, NIH, DHHS

  NDA                    New Drug Application

  NEJM                   New England Journal of Medicine

  NIAID                  National Institute of Allergy and Infectious
                         Diseases, NIH, DHHS

  NIH                    National Institutes of Health

  OCRA                   Office of Clinical Research Affairs, DMID,
                         NIAID, NIH, DHHS

  OHRP                   Office for Human Research Protections

  OHSR                   Office for Human Subjects Research

  ORA                    Office of Regulatory Affairs, DMID, NIAID, NIH,
                         DHHS

  PHI                    Protected Health Information

  PI                     Principal Investigator

  PK                     Pharmacokinetics

  QA                     Quality Assurance

  QC                     Quality Control

  SAE                    Serious Adverse Event/Serious Adverse Experience

  SMC                    Safety Monitoring Committee

  SOP                    Standard Operating Procedure

  US                     United States

  WHO                    World Health Organization
  ---------------------- ------------------------------------------------

*Please modify list to include your protocol-specific terms.*

[]{#__RefHeading___Toc114558135 .anchor}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:**        |                                               |
+----------------------+-----------------------------------------------+

**Schematic of Study Design**:

# Key Roles

  ---------------------- ------------------------------------------------
  **Individuals:**       

                         **Protocol Champion:**

                         **Principal Investigator:**

                         **Medical Monitor:** *(if applicable)*

  **Institutions:**      

  **Optional:**          
  ---------------------- ------------------------------------------------

# Background Information and Scientific Rationale

## Background Information

## Rationale

## Potential Risks and Benefits

### Potential Risks

### Known Potential Benefits

# Objectives

## Study Objectives

## Study Outcome Measures

### Primary Outcome Measures

### Secondary Outcome Measures

# Study Design

## Substudies (if applicable)

# Study Enrollment and Withdrawal

## Subject Inclusion Criteria

## Subject Exclusion Criteria

## Treatment Assignment Procedures

### Randomization Procedures

### Masking Procedures

### Reasons for Withdrawal

### Handling of Withdrawals

### Termination of Study 

# Study Intervention/Investigational Product

## Study Product Description

### Acquisition

### Formulation, Packaging, and Labeling

### Product Storage and Stability

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

## Modification of Study Intervention/Investigational Product for a Participant

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

## Assessment of Subject Compliance with Study Intervention/Investigational Product 

## Concomitant Medications/Treatments

# Study Schedule

## Screening 

## Enrollment/Baseline

## Follow-up 

## Final Study Visit

## Early Termination Visit

## Unscheduled Visit 

# Study Procedures/Evaluations

## Clinical Evaluations

## Laboratory Evaluations

### Clinical Laboratory Evaluations

### Special Assays or Procedures

### Specimen Preparation, Handling, and Shipping

#### Instructions for Specimen Preparation, Handling, and Storage

#### Specimen Shipment

# Assessment of Safety

## Specification of Safety Parameters

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

### Adverse Events

### Reactogenicity (for Vaccine Studies and Some Therapeutic Trials)

### Serious Adverse Events

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

## Reporting Procedures

### Regulatory Reporting for Studies Conducted Under DMID‑Sponsored IND

### Regulatory Reporting for Studies Not Conducted Under DMID‑Sponsored IND

### Other Adverse Events (if applicable)

### Reporting of Pregnancy

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

## Halting Rules

## Safety Oversight (ISM plus SMC or DSMB)

# Clinical Monitoring

## Site Monitoring Plan

# Statistical Considerations

## Study Hypotheses

## Sample Size Considerations

## Planned Interim Analyses (if applicable)

### Safety Review 

### Immunogenicity or Efficacy Review

## Final Analysis Plan

# Source Documents and Access to Source Data/Documents

# Quality Control and Quality Assurance

# Ethics/Protection of Human Subjects

## Ethical Standard

## Institutional Review Board

## Informed Consent Process

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

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

## Subject Confidentiality

## Study Discontinuation

## Future Use of Stored Specimens

# Data Handling and Record Keeping

## Data Management Responsibilities

## Data Capture Methods

## Types of Data

## Timing/Reports

## Study Records Retention

## Protocol Deviations

# Publication Policy

# Literature References

[]{#__RefHeading___Toc114558226 .anchor}SupplementS/Appendices

[]{#__RefHeading___Toc114558227 .anchor}Appendix A: Schedule of Events