Study Logo/Sponsor Logo/Funder Logo

Study logo/Sponsor logo/Funder logo

FULL/LONG TITLE OF THE STUDY

SHORT STUDY TITLE / ACRONYM

PROTOCOL VERSION NUMBER AND DATE

 This protocol has regard for the HRA guidance and order of content

RESEARCH REFERENCE NUMBERS Page 1 of 12 TEM74 Keele CTU Non-CTIMP Protocol Template v1.0 06-Feb-2017 IRAS Number:

ISRCTN / Clinical trials.gov Number:

Sponsor Number:

Funder’s Number: 1. SIGNATURE PAGE The undersigned confirm that the following protocol has been agreed and accepted and that the Chief Investigator agrees to conduct the trial in compliance with the approved protocol, GCP guidelines, the Sponsor’s SOPs, and other regulatory requirements as amended. I agree to ensure that the confidential information contained in this document will not be used for any other purpose other than the evaluation or conduct of the clinical investigation without the prior written consent of the Sponsor I also confirm that I will make the findings of the study publically available through publication or other dissemination tools without any unnecessary delay and that an honest accurate and transparent account of the study will be given; and that any discrepancies from the study as planned in this protocol will be explained.

For and on behalf of the Study Sponsor: Signature: Date: ...... /...... /...... Name (please print): ...... Position: ......

Chief Investigator: Signature: ...... Date: ...... /...... /...... Name (please print): ......

of 12 TEM73 Keele CTU Non-CTIMP Protocol Template v1.0 06-Feb-2017 3. LIST of CONTENTS

GENERAL INFORMATION Page No. TITLE PAGE RESEARCH REFERENCE NUMBERS SIGNATURE PAGE LIST of CONTENTS LIST OF ABBREVIATIONS KEY TRIAL/STUDY CONTACTS TRIAL/STUDY SUMMARY TRIAL FLOW CHART SECTION 1. BACKGROUND 2. RATIONALE 3. OBJECTIVES AND OUTCOME MEASURES/ENDPOINTS 4. TRIAL DESIGN 5. STUDY SETTING 6. ELIGIBILITY CRITERIA 7. TRIAL/STUDY* PROCEDURES 8. STATISTICS AND DATA ANALYSIS 9. DATA HANDLING 10. MONITORING & AUDIT 11. ETHICAL AND TRIAL ADMINISTRATION 12. DISSEMINATION POLICY 13. REFERENCES 14. APPENDICIES LIST OF ABBREVIATIONS* Items as appropriate Define all unusual or ‘technical’ terms related to the trial/study*. Add or delete as appropriate. Maintain alphabetical order for ease of reference. AE Adverse Event AR Adverse Reaction CI Chief Investigator CRF Case Report Form CRO Contract Research Organisation CTA Clinical Trial Authorisation DMC Data Monitoring Committee DSUR Development Safety Update Report GCP Good Clinical Practice ICF Informed Consent Form DMC Independent Data Monitoring Committee ISF Investigator Site File ISRCTN International Standard Randomised Controlled Trials Number NIMP Non-Investigational Medicinal Product PI Principal Investigator PIC Participant Identification Centre PIS Participant Information Sheet QA Quality Assurance QC Quality Control RCT Randomised Control Trial REC Research Ethics Committee SAE Serious Adverse Event SAR Serious Adverse Reaction SDV Source Data Verification SMF* Study Master File SMG* Study Management Group SOP Standard Operating Procedure SSI Site Specific Information SUSAR Suspected Unexpected Serious Adverse Reaction TMG* Trial Management Group TSC Trial Steering Committee TMF* Trial Master File

of 12 TEM74 Keele CTU Non-CTIMP Protocol Template v1.0 06-Feb-2017 4. KEY TRIAL/STUDY* CONTACTS *Delete as appropriate Insert full details of the key trial contacts including the following (where applicable) Chief Investigator Full contact details including phone, email and fax numbers Principal Investigator Full contact details including phone, email and fax numbers Sponsor Dr Clark Crawford Head of Research Integrity, Directorate of Engagement & Partnerships, Innovation Centre 2, Keele University, Staffordshire, ST5 5NH 01782 733371 [email protected] Joint-sponsor(s)/co-sponsor(s) Full contact details including phone, email and fax numbers of ALL organisations assuming sponsorship responsibilities as a joint- or co-sponsor/s (If applicable) Funder(s) Names and contact details of ALL organisations providing funding and/or support in kind for this trial Trial/Study* Management Keele Clinical Trials Unit (CTU), David Weatherall Building, Keele University, Staffordshire, ST5 5BG 01782 732916 [email protected] Key Protocol Contributors Full contact details including phone, email and fax numbers (If applicable) Lead Statistician Full contact details including phone, email and fax numbers Committees Full contact details including phone, email and fax numbers

of 12 TEM74 Keele CTU Non-CTIMP Protocol Template v1.0 06-Feb-2017 5. TRIAL/STUDY* SUMMARY It may be useful to include a brief synopsis of the trial/study for quick reference. Complete information and, if required, add additional rows. Trial/Study* Title Internal Ref. Number (or short title)

Trial/Study* Design

Trial Intervention (where applicable)

Trial/Study* Participants

Planned Sample Size

Treatment duration

Follow up duration

Planned Trial Period

Objectives Outcome Measures Primary

Secondary

of 12 TEM74 Keele CTU Non-CTIMP Protocol Template v1.0 06-Feb-2017 Page 8 of 12 TEM74 Keele CTU Non-CTIMP Protocol Template v1.0 06-Feb-2017 6. TRIAL/STUDY* FLOW CHART

of 12 TEM74 Keele CTU Non-CTIMP Protocol Template v1.0 06-Feb-2017 7. 1 BACKGROUND

8. 2 RATIONALE

9. 3 OBJECTIVES AND OUTCOME MEASURES/ENDPOINTS 3.1 Primary objective 3.2 Secondary objectives 3.3 Outcome measures/endpoints 3.4 Primary endpoint/outcome 3.5 Secondary endpoints/outcomes 3.6 Exploratory endpoints/outcomes

10. 4 TRIAL/STUDY* DESIGN 4.1 Interventions/Treatments 4.2 Study Training

11. 5 STUDY SETTING

12. 6 ELIGIBILITY CRITERIA 6.1 Inclusion criteria 6.2 Exclusion criteria 13.

14. 7 TRIAL/STUDY* PROCEDURES 7.1 Recruitment 7.1.1 Patient identification 7.1.2 Screening 7.2 Consent 7.3 The randomisation scheme 7.4 Blinding 7.5 Unblinding 7.6 Baseline data 7.7 Trial/Study* assessments 7.8 Long term follow-up assessments 7.9 Qualitative assessments – Nested studies 7.10 Withdrawal criteria

of 12 TEM74 Keele CTU Non-CTIMP Protocol Template v1.0 06-Feb-2017 7.11 Storage and analysis of samples 15. 7.12 End of trial/study*

16. 8 STATISTICS AND DATA ANALYSIS 8.1 Sample size calculation 8.2 Planned recruitment rate 8.3 Statistical analysis plan 8.3.1 Summary of baseline data and flow of patients 8.3.2 Primary outcome analysis 8.3.3 Secondary outcome analysis 8.4 Subgroup analyses 8.5 Adjusted analysis 8.6 Interim analysis and criteria for the premature termination of the trial 8.7 Subject population 8.8 Procedure(s) to account for missing or spurious data 8.9 Other statistical considerations. 8.11 Economic evaluation

17. 9 DATA HANDLING 18. 9.1 Data collection tools and source document identification 19. 9.2 Data handling and record keeping 20. 9.3 Access to Data 9.4 Data Sharing Agreements 9.5 Archiving

10 MONITORING & AUDIT 10.1 Trial/Study* Management 10.1.1 Trial Steering Committee (TSC) members 10.1.2 Data Monitoring Committee (DMC) members 10.2 Monitoring arrangements 10.3 Auditing procedures 10.4 Safety Reporting 10.5 Trial timeline

21. 11 ETHICAL AND REGULATORY CONSIDERATIONS 11.1 Research Ethics Committee (REC) review & reports

of 12 TEM74 Keele CTU Non-CTIMP Protocol Template v1.0 06-Feb-2017 11.2 Peer review 11.3 Public and Patient Involvement 11.4 Regulatory Compliance 11.5 Protocol compliance 11.6 Notification of Serious Breaches to GCP and/or the protocol 11.7 Data protection and patient confidentiality 11.8 Financial and other competing interests for the chief investigator, PIs at each site and committee members for the overall trial/study* management 11.9 Indemnity 11.10 Amendments 11.11 Post trial care 11.12 Access to the final trial dataset

12 DISSEMINIATION POLICY 12.1 Dissemination policy 12.2 Authorship eligibility guidelines and any intended use of professional writers

13 REFERENCES

14. APPENDICIES 14.1 Appendix 1 - Study management / responsibilities (For multi-centre trials/studies* only)

of 12 TEM74 Keele CTU Non-CTIMP Protocol Template v1.0 06-Feb-2017