Insert Title of the Protocol

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iNSERT tITLE OF THE PROTOCOL

[Include phase (e.g. phase I, phase II, etc.), design (e.g. randomized, double blind, placebo controlled, etc), if the study is multi-centered, the investigational drug or device, and target disease(s)]

Example title:

A phase II, randomized, double-blind, placebo-controlled, multi-center study of the effects of XXXX on infarct size in subjects with diabetes mellitus presenting with acute myocardial infarction.

CONFIDENTIAL

This document is confidential and the property of the University of Minnesota. No part of it may be transmitted, reproduced, published, or used by other persons without prior written authorization from the study sponsor.

Table of Contents

Study Summary 1

1 Introduction 2

1.1 Background 2

1.2 Investigational Agent 2

1.3 Preclinical Data 2

1.4 Clinical Data to Date 2

1.5 Dose Rationale and Risk/Benefits 2

2 Study Objectives 2

3 Study Design 3

3.1 General Design 3

3.2 Primary Study Endpoints 3

3.3 Secondary Study Endpoints 3

3.4 Primary Safety Endpoints 3

4 Subject Selection and Withdrawal 3

4.1 Inclusion Criteria 3

4.2 Exclusion Criteria 3

4.3 Subject Recruitment and Screening 4

4.4 Early Withdrawal of Subjects 4

4.4.1 When and How to Withdraw Subjects 4

4.4.2 Data Collection and Follow-up for Withdrawn Subjects 4

5 Study Drug 4

5.1 Description 4

5.2 Treatment Regimen 4

5.3 Method for Assigning Subjects to Treatment Groups 5

5.4 Preparation and Administration of Study Drug 5

5.5 Subject Compliance Monitoring 5

5.6 Prior and Concomitant Therapy 5

5.7 Packaging 5

5.8 Blinding of Study Drug 5

5.9 Receiving, Storage, Dispensing and Return 5

5.9.1 Receipt of Drug Supplies 5

5.9.2 Storage 6

5.9.3 Dispensing of Study Drug 6

5.9.4 Return or Destruction of Study Drug 6

6 Study Procedures 6

6.1 Visit 1 7

6.2 Visit 2 7

6.3 etc. 7

7 Statistical Plan 7

7.1 Sample Size Determination 7

7.2 Statistical Methods 7

7.3 Subject Population(s) for Analysis 7

8 Safety and Adverse Events 7

8.1 Definitions 7

8.2 Recording of Adverse Events 9

8.3 Reporting of Serious Adverse Events 10

8.3.1 Study Sponsor Notification by Investigator 10

8.3.2 EC/IRB Notification by Investigator 10

8.3.3 FDA Notification by Sponsor 10

8.4 Unblinding Procedures 11

8.5 Stopping Rules 11

8.6 Medical Monitoring 11

8.6.1 Internal Data and Safety Monitoring Board 11

8.6.2 Independent Data and Safety Monitoring Board 12

9 Data Handling and Record Keeping 12

9.1 Confidentiality 12

9.2 Source Documents 13

9.3 Case Report Forms 13

9.4 Records Retention 13

10 Study Monitoring, Auditing, and Inspecting 14

10.1 Study Monitoring Plan 14

10.2 Auditing and Inspecting 14

11 Ethical Considerations 14

12 Study Finances 15

12.1 Funding Source 15

12.2 Conflict of Interest 15

12.3 Subject Stipends or Payments 15

13 Publication Plan 15

14 References 15

15 Attachments 15

List of Abbreviations

List all abbreviations used in protocol

AE Adverse Event

CFR Code of Federal Regulations

CRF Case Report Form

DSMB Data and Safety Monitoring Board

DSMP Data and Safety Monitoring Plan

FDA Food and Drug Administration

GCP Good Clinical Practice

HIPAA Health Insurance Portability and Accountability Act of 1996

ICH International Conference on Harmonisation

IDS Investigational Drug Services

IRB Institutional Review Board

PHI Protected Health Information

SAE Serious Adverse Event

CONFIDENTIAL

This material is the property of the University of Minnesota. Do not disclose or use except as authorized in writing by the study sponsor

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Study Summary

1  Introduction

The introduction should open with remarks that state that this document is a clinical research protocol and the described study will be conducted in compliance with the protocol, Good Clinical Practices standards and associated Federal regulations, and all applicable University research requirements. The rest of the introduction is broken out into subsections. Example language for the first paragraph under “Introduction” and before the section “1.1 Background”:

This document is a protocol for a human research study. This study will be conducted according to US and international standards of Good Clinical Practice (FDA Title 21 part 312 or 812 and International Conference on Harmonisation guidelines), applicable government regulations and Institutional research policies and procedures.

1.1  Background

This section should contain a background discussion of the target disease state to which the investigational product(s) hold promise, and any pathophysiology relevant to potential study treatment action.

1.2  Investigational Agent

This section should contain a description of the investigational product, its make-up, chemical properties and any relevant physical properties, including any available pharmacologic data. (A good example for this section is the “Description” and “Pharmacology” sections for drugs listed in the Physicians’ Desk Reference)

1.3  Preclinical Data

Summarize the available non-clinical data (published or available unpublished data) that could have clinical significance.

1.4  Clinical Data to Date

Summarize the available clinical study data (published or available unpublished data) with relevance to the protocol under construction -- if none is available, include a statement that there is no available clinical research data to date on the investigational product.

1.5  Dose Rationale and Risk/Benefits

Describe the rationale used for selection of the dose for the protocol under construction. This should be based on non-clinical and clinical data available to date. It should include justification for route of administration, dosage, dosage regimen, and dosage period. Discuss why the risks to subjects are reasonable in relation to the anticipated benefits and/or knowledge that might reasonably be expected from the results.

2  Study Objectives

Describe the overall objectives and purpose of the study. This should include both primary and any secondary objectives, e.g.:

Primary Objective

To assess the efficacy of XXXX on decreasing infarct size as measured by Sestamibi scanning.

Secondary Objective

To assess the safety and tolerability of two doses of XXXX in subjects with acute myocardial infarction.

3  Study Design

3.1  General Design

Include:

·  The type/design of the study (e.g. Phase, randomized, double-blind, parallel group, etc.)

·  Number of participants

·  A schematic diagram of the trial design, procedures and stages is advisable

·  Expected duration of subject participation

·  A description of the sequence and duration of all trial periods including follow-up, if any

3.2  Primary Study Endpoints

Describe the primary endpoint to be analyzed in the study (e.g. could be safety or efficacy, depending on the main objective of the study).

3.3  Secondary Study Endpoints

Describe any secondary endpoints to be analyzed in the study

3.4  Primary Safety Endpoints

All studies should include the primary safety endpoints to be measured. If the primary objective of the study is a safety study and therefore the Primary Endpoint(s) of the study are safety endpoints, then it should be noted in section 3.1 above and this subsection 3.3 can be deleted.

4  Subject Selection and Withdrawal

4.1  Inclusion Criteria

Create a numbered list of criteria subjects must meet to be eligible for study enrollment (e.g. age, gender, target disease, concomitant disease if required, etc.) Generally should include items such as: “subjects are capable of giving informed consent”, or if appropriate, “have an acceptable surrogate capable of giving consent on the subject’s behalf.”

4.2  Exclusion Criteria

Create a numbered list of criteria that would exclude a subject from study enrollment. If appropriate, should generally include that subjects cannot be homeless persons, or have active drug/alcohol dependence or abuse history. If exposure to certain medications or treatments at screening is prohibited, that must be noted in the exclusion criteria—if these are also prohibited concomitant medications during the study period that should be noted here as well.

Include whether pregnancy or breastfeeding is an exclusion.

4.3  Subject Recruitment and Screening

Describe how subjects will be recruited for the study, e.g. from investigator or sub-investigator clinical practices, referring physicians, advertisement, etc. Note in this section that information to be disseminated to subjects (handouts, brochures, etc.) and any advertisements must be approved by the IRB for the site; include a sample of such information in the attachment section of the protocol. Also in this section, list any screening requirements such as laboratory or diagnostic testing necessary to meet any noted inclusion or exclusion criteria (greater detail of timing, etc. can be included later in section 6 “Study Procedures” section of the protocol).

4.4  Early Withdrawal of Subjects

4.4.1  When and How to Withdraw Subjects

Describe the scenarios under which a subject may be withdrawn from the study prior the expected completion of that subject (e.g. safety reasons, failure of subject to adhere to protocol requirements, subject consent withdrawal, disease progression, etc.) Also, if abrupt termination of study treatment could affect subject safety (e.g. in an antihypertensive study, abrupt withdrawal without other intervention might cause hypertensive rebound), describe procedure to transition subject off the study drug or to alternate therapy.

4.4.2  Data Collection and Follow-up for Withdrawn Subjects

Even though subjects may be withdrawn prematurely from the study, it is imperative to collect at least survival data on such subjects throughout the protocol defined follow-up period for that subject (though careful thought should be give to the full data set that should to be collected on such subjects to fully support the analysis). Such data is important to the integrity of the final study analysis since early withdrawal could be related to the safety profile of the study drug. If a subject withdraws consent to participate in the study, attempts should be made to obtain permission to record at least survival data up to the protocol-described end of subject follow-up period. IT MUST BE A HIGH PRIORITY TO TRY TO OBTAIN AT LEAST SURVIVAL DATA ON ALL SUBJECTS LOST TO FOLLOW-UP AND TO NOTE WHAT METHODS SHOULD BE USED BEFORE ONE CAN STATE THE SUBJECT IS TRULY LOST TO FOLLOW-UP (e.g. number of phone calls to subject, phone calls to next-of-kin if possible, certified letters, etc.).

5  Study Drug

5.1  Description

This section should be a very brief synopsis of section 1.2 “Investigational agent”, along with how the how the drug product will appear (e.g. as tablets or capsules of “X”mg, as a liquid with “X”mg dissolved in 10ml 5% dextrose and water, etc.)

5.2  Treatment Regimen

Describe dose, route of administration, and length of time to be infused (if applicable). . Be specific with any pre-medications and/or concurrent medications given. State the number of planned cycles or treatment duration.

5.3  Method for Assigning Subjects to Treatment Groups

Describe how a randomization number and associated treatment assignment will be made. This could be selection of a sequentially numbered drug kit/box, or communication with a randomization center that assigns a number associated with a specific treatment kit/box, etc.

5.4  Preparation and Administration of Study Drug

Describe in detail all the steps necessary to properly prepare study treatment. Include whether the drug preparation will be done in a pharmacy or by a study team member. Fully describe how the study treatment is to be administered. If study drug is stored, mixed/prepared or dispensed from the Investigational Drug Service, that should be noted here, including the assigned number from IDS.

5.5  Subject Compliance Monitoring

Describe how the study team will assess and track subject compliance with the study treatment regimen, and what procedures must be followed for any subject who is significantly non-compliant with the study treatment regimen.

5.6  Prior and Concomitant Therapy

In this section, describe:

·  What prior and/or concomitant medical therapy will be collected (if applicable)

·  Which concomitant medicines/therapies (including rescue therapies) are permitted during the study

·  Which concomitant medicines/therapies are not permitted during the study (if applicable)

5.7  Packaging

·  Describe how the study drug and any comparator agent will be packaged along with the amounts (e.g. “20 ml vials containing 30 mg”, or “bottles containing 30 tablets of …”, etc.) along with any associated labeling

·  Describe if drug is to be shipped in bulk (e.g. Study drug will be shipped in boxes of 30 vials each, etc.) or as separate subject-specific kits/boxes