Clinical Study Report [Study Title] [Study number] [Dd month yyyy] CONFIDENTIAL Signature pages for clinical study report I have read this report and confirm that to the best of my knowledge it accurately describes the conduct and results of the study. Signed: Date: ____/____/______ Date: ____/____/______ Date: ____/____/______ Date: ____/____/______ Date: ____/____/______ Print name: Affiliation: Address: Signed: Print name: Affiliation: Address: Signed: Print name: Affiliation: Address: Signed: Print name: Affiliation: Address: Signed: Print name: Affiliation: Address: Clinical Study Report Template Page 2 of 22 1 TITLE PAGE Study title: Name of Test Drug: Indication studied: Study description: Sponsors: Protocol: Clinical Phase: Study dates: Investigators: Medical Officer: Sponsor signatory: GCP Statement: This study was performed in compliance with ICH Good Clinical Practise (GCP) including the archiving of essential documents Date of report: Clinical Study Report Template Page 3 of 22 2 SYNOPSIS NAME OF SPONSOR NAME OF FINISHED PRODUCT N/A NAME OF ACTIVE INGREDIENT(S) INDIVIDUAL STUDY TABLE REFERRING TO MODULE 5 OF THE CTD (FOR NATIONAL AUTHORITY USE ONLY) Volume: Page: Title of Study Investigator(s) Study centre(s) Publication N/A Study period From: To: Primary Objective Objectives Phase of development Phase Secondary Objective Methodology Number of patients Planned: Analysed: Diagnosis and main criteria for inclusion Test product, dose and mode of administration Duration of treatment Criteria for evaluation Primary: Secondary: Statistical methods Clinical Study Report Template Page 4 of 22 NAME OF COMPANY NAME OF FINISHED PRODUCT NAME OF ACTIVE INGREDIENT(S) N/A INDIVIDUAL STUDY TABLE REFERRING TO MODULE 5 OF THE CTD (FOR NATIONAL AUTHORITY USE ONLY) Volume: Page: SUMMARY CONCLUSIONS EFFICACY RESULTS SAFETY RESULTS CONCLUSION DATE OF THE REPORT: Clinical Study Report Template Page 5 of 22 3 TABLE OF CONTENTS 1 TITLE PAGE .............................................................................................................................. 3 2 SYNOPSIS ................................................................................................................................. 4 3 TABLE OF CONTENTS ............................................................................................................. 6 4 LIST OF ABBREVIATIONS & DEFINITION OF TERMS .......................................................... 8 5 ETHICS AND REGULATORY APPROVAL .............................................................................. 9 5.1 INDEPENDENT ETHICS COMMITTEE APPROVAL ............................................................9 5.2 ETHICAL CONDUCT OF THE STUDY ..................................................................................9 5.3 PATIENT INFORMATION AND CONSENT ...........................................................................9 5.4 REGULATORY APPROVAL ................................................................................................10 6 INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE ....................................... 10 7 INTRODUCTION ...................................................................................................................... 11 7.1 [THERAPEUTIC AREA] .......................................................................................................11 7.2 RATIONALE FOR THE STUDY ...........................................................................................11 8 STUDY OBJECTIVES.............................................................................................................. 12 9 INVESTIGATIONAL PLAN ...................................................................................................... 12 9.1 OVERALL STUDY DESIGN AND PLAN ..............................................................................12 9.1.1 STUDY TIMING.............................................................................................................. 12 9.1.2 STUDY LOCATION ........................................................................................................ 12 9.2 DISCUSSION OF STUDY DESIGN .....................................................................................12 9.3 SELECTION OF STUDY POPULATION .............................................................................12 9.3.1 INCLUSION CRITERIA .................................................................................................. 12 9.3.2 EXCLUSION CRITERIA ................................................................................................. 12 9.3.3 WITHDRAWAL OF PATIENTS FROM THERAPY OR ASSESSMENT ........................ 12 9.4 TREATMENTS .....................................................................................................................13 9.4.1 TREATMENTS ADMINISTERED ................................................................................... 13 9.4.2 DESCRIPTION OF INVESTIGATIONAL PRODUCTS .................................................. 13 9.4.2.1 9.4.2.2 9.4.3 9.4.4 9.4.5 9.4.6 9.4.7 [PRIME] ......................................................................................... 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METHOD OF ASSIGNING PATIENTS TO TREATMENT GROUPS ............................ 13 SELECTION OF DOSES IN THE STUDY ..................................................................... 13 SELECTION AND TIMING OF DOSE FOR INDIVIDUAL PATIENTS ........................... 13 PRIOR AND CONCOMITANT THERAPY ..................................................................... 13 TREATMENT COMPLIANCE ........................................................................................ 13 9.5 EFFICACY AND SAFETY VARIABLES ...............................................................................13 9.5.1 EFFICACY AND SAFETY MEASUREMENTS ASSESSED .......................................... 13 9.5.2 APPROPRIATENESS OF MEASUREMENTS .............................................................. 16 9.5.3 IMMUNOGENICITY VARIABLES .................................................................................. 16 9.6 DATA QUALITY ASSURANCE ............................................................................................16 9.7 STATISTICAL METHODS PLANNED IN THE PROTOCOL & DETERMINATION OF SAMPLE SIZE ................................................................................................................................16 Clinical Study Report Template Page 6 of 22 9.7.1 9.7.2 STATISTICAL AND ANALYTICAL PLANS .................................................................... 16 DETERMINATION OF SAMPLE SIZE ........................................................................... 16 9.8 CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED ANALYSES ...................16 9.8.1 PROTOCOL AMENDMENTS ........................................................................................ 16 10 STUDY POPULATION ............................................................................................................. 16 10.1 DISPOSITION OF PATIENTS..............................................................................................16 10.2 PROTOCOL DEVIATIONS ..................................................................................................18 11 RESULTS ................................................................................................................................. 19 11.1 DATA SETS ANALYSED .....................................................................................................19 11.2 DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS ......................................19 11.3 MEASUREMENTS OF TREATMENT COMPLIANCE .........................................................19 11.4 STUDY DURATION .............................................................................................................19 11.5 IMMUNOGENECITY RESULTS AND TABULATIONS OF PATIENT DATA.......................20 11.5.1 ANALYSIS OF IMMUNOGENECITY ............................................................................. 20 11.5.2 STATISTICAL/ANALYTICAL ISSUES ........................................................................... 20 11.5.2.1 11.5.3 11.5.4 11.5.5 11.5.6 HANDLING OF DROPOUTS OR MISSING DATA ..................................................................... 20 TABULATION OF INDIVIDUAL RESPONSE DATA ...................................................... 20 VACCINE DOSE AND RELATIONSHIP TO RESPONSE ............................................. 20 BY-PATIENT DISPLAYS ............................................................................................... 20 IMMUNOGENECITY CONCLUSIONS .......................................................................... 20 12 SAFETY EVALUATION ........................................................................................................... 20 12.1 EXTENT OF EXPOSURE ....................................................................................................20 12.2 ADVERSE EVENTS (AE’s) ..................................................................................................20 12.2.1 BRIEF SUMMARY OF ADVERSE EVENTS ................................................................. 20 12.2.2 TREATMENT EMERGENT ADVERSE EVENTS .......................................................... 20 12.2.3 TREATMENT RELATED ADVERSE EVENTS .............................................................. 20 12.2.4 IMMUNISATION TOLERANCE ...................................................................................... 20 12.3 SERIOUS ADVERSE EVENTS AND OTHER SIGNIFICANT ADVERSE EVENTS ...........21 12.4 DEATHS ...............................................................................................................................21 12.5 CLINICAL LABORATORY EVALUATION ............................................................................21 12.5.1 EVALUATION OF EACH LABORATORY PARAMETER .............................................. 21 12.6 VITAL SIGNS, PHYSICAL FINDINGS AND OTHER OBSERVATIONS RELATED TO SAFETY 21 12.7 CONCOMITTANT MEDICATION USE ................................................................................21 12.8 SAFETY CONCLUSIONS ....................................................................................................21 13 DISCUSSION AND OVERALL CONCLUSIONS .................................................................... 21 14 TABLES, FIGURES AND GRAPHS ........................................................................................ 21 15 REFERENCES ......................................................................................................................... 21 16 APPENDICES .......................................................................................................................... 21 Clinical Study Report Template Page 7 of 22 4 LIST OF ABBREVIATIONS & DEFINITION OF TERMS Clinical Study Report Template Page 8 of 22 5 ETHICS AND REGULATORY APPROVAL 5.1 INDEPENDENT ETHICS COMMITTEE APPROVAL The study protocol and all its amendments, and the patient information sheet(s) were reviewed and approved by the appropriate independent ethics committees as detailed in table one below. Table I: Ethics committees Centre name and number Investigator Ethics committee Chairman Date of approval of the final protocol Date of approval of amendment 1 Date of approval of amendment 2 Date of approval of amendment 3 5.2 ETHICAL CONDUCT OF THE STUDY The study was performed in accordance with the current version of the declaration of Helsinki (52nd WMA General Assembly, Edinburgh, Scotland, October 2000). The trial was conducted in agreement with the International Conference on Harmonisation (ICH) guidelines on Good Clinical Practise (GCP) 5.3 PATIENT INFORMATION AND CONSENT All patients provided written informed consent to participate in the study prior to being screened. The patient information sheet detailed the procedures involved in the study (aims, methodology. potential risks, anticipated benefits) and the investigator explained these to each patient. The patient signed the consent form to indicate that the information had been explained and understood. The patient was then allowed time to consider the information presented before signing and dating the informed consent form to indicate that they fully understood the information, and willingly volunteered to participate in the study. The patient was given a copy of the informed consent form for their information. The original copy of the informed consent was kept in a confidential file in the Investigators centre records. A sample of the patient information sheet and consent form can be found at appendix [insert] Clinical Study Report Template Page 9 of 22 5.4 REGULATORY APPROVAL The study was performed in compliance with the requirements of the [regulatory authorities]. The study gained full regulatory approval from the on [date], SPONSOR was issued with the following EudraCT number [ ]. A copy can be found in appendix [insert] The study gained full approval from [EC] on [insert] a copy can be found in appendix [insert] 6 INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE Table II shows the principal study personnel involved in the study. Table II: Principal study personnel Title Principal Investigator Principal investigator Sponsor Name and affiliation Sponsor Project Managers Project Leaders Clinical Research Associate(s) Medical Adviser Laboratory investigator Data Management Clinical Study Report Template Page 10 of 22 7 INTRODUCTION 7.1 [THERAPEUTIC AREA] 7.2 RATIONALE FOR THE STUDY Clinical Study Report Template Page 11 of 22 8 STUDY OBJECTIVES Primary Objective Secondary Objective 9 INVESTIGATIONAL PLAN 9.1 OVERALL STUDY DESIGN AND PLAN 9.1.1 STUDY TIMING Figure I Schematic chart of Protocol 9.1.2 STUDY LOCATION This study was conducted at the following locations: 9.2 DISCUSSION OF STUDY DESIGN 9.3 SELECTION OF STUDY POPULATION 9.3.1 INCLUSION CRITERIA 9.3.2 EXCLUSION CRITERIA 9.3.3 WITHDRAWAL OF PATIENTS FROM THERAPY OR ASSESSMENT Patients were free to withdraw from the study at any time without giving a reason. Patients were advised that if they requested to withdraw from the study, at any time during the trial, then this would have no negative consequences. The investigator could also withdraw patients from the trial if they deemed it appropriate for safety or ethical reasons or if it was considered to be to be detrimental to the wellbeing of the patient. Patients who withdrew or were withdrawn underwent a final evaluation at [visit]. Patients who did not complete the study through to [visit], unless removed due to toxicity, could have been replaced Clinical Study Report Template Page 12 of 22 Full documentation was made of any withdrawals that occurred during the study in the CRF. The Investigator documented the date and time of the withdrawal and results of any assessments made at this time. If the patient withdrew because of an adverse event (AE) or a serious adverse event (SAE) then details were forwarded to the Ethics committee as required. The investigator also forwarded details to SPONSOR. SPONSOR forwarded details to the regulatory authorities as appropriate. 9.4 TREATMENTS 9.4.1 TREATMENTS ADMINISTERED 9.4.2 DESCRIPTION OF INVESTIGATIONAL PRODUCTS 9.4.3 METHOD OF ASSIGNING PATIENTS TO TREATMENT GROUPS 9.4.4 SELECTION OF DOSES IN THE STUDY 9.4.5 SELECTION AND TIMING OF DOSE FOR INDIVIDUAL PATIENTS 9.4.6 PRIOR AND CONCOMITANT THERAPY 9.4.7 TREATMENT COMPLIANCE All study treatment was administered by the study investigator or designated member of staff. To ensure drug accountability the investigator or designated deputy maintained accurate records of the dates and amounts of drug received, to whom it was dispensed and accounts of any supplies which were accidentally or deliberately destroyed; these details were recorded on a drug accountability form. All unused clinical supplies and the drug accountability forms were returned to SPONSOR at the end of the study. 9.5 EFFICACY AND SAFETY VARIABLES 9.5.1 EFFICACY AND SAFETY MEASUREMENTS ASSESSED Performance status CT Scan (Disease status) ECG Clinical Assessment of Injection Site Clinical Examination Vital Signs Safety Laboratory Tests Clinical Study Report Template Page 13 of 22 Haematology Serum chemistry Urinalysis HBV, HCV, HIV and pregnancy Cellular immunology Table III shows the schedule of examinations and procedures. Clinical Study Report Template Page 14 of 22 Table III [Schedule of examinations and procedures] Study day Clinical Study Report Template Page 15 of 22 9.5.2 APPROPRIATENESS OF MEASUREMENTS 9.5.3 IMMUNOGENICITY VARIABLES 9.6 DATA QUALITY ASSURANCE 9.7 STATISTICAL METHODS PLANNED IN THE PROTOCOL & DETERMINATION OF SAMPLE SIZE 9.7.1 STATISTICAL AND ANALYTICAL PLANS 9.7.2 DETERMINATION OF SAMPLE SIZE 9.8 9.8.1 CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED ANALYSES PROTOCOL AMENDMENTS 10 STUDY POPULATION 10.1 DISPOSITION OF PATIENTS Clinical Study Report Template Page 16 of 22 PATIENTS SCREENED N= SCREENING FAILURES N= PATIENTS RANDOMISED N= GROUP A N= COMPLETED N= GROUP B N= WITHDRAWN N= COMPLETED N= WITHDRAWN N= LOST TO FOLLOW UP (0) ADVERSE EVENT (0) DEATH (0 ) OTHER ( ) RECEIVED [Prime] RECEIVED [Prime] RECEIVED [Boost] RECEIVED [Boost] ATTENDED [visit] COMPLETED [Visit] Table IV RECEIVED [Prime] RECEIVED [Prime] RECEIVED [Boost] RECEIVED [Boost] ATTENDED [visit] COMPLETED [Visit] Disposition of patients Group A (N=) Group B (N=) Total (N=) Enrolled Received at least one injection Received all [x] injections and attended [vist] Completed [visit] Withdrawn: Lost to follow up Adverse event Death Other Source Data: Listing xx: Clinical Study Report Template Page 17 of 22 10.2 PROTOCOL DEVIATIONS Table V gives details of study protocol deviations. Table V Protocol deviations Deviation Entry criteria Withdrawal criteria Incorrect dosing regimen Concomitant treatment/medication Other Site: Site: 0 0 0 0 0 0 0 0 0 0 Full details of the protocol deviations can be found in appendix 16.2.2 Clinical Study Report Template Page 18 of 22 11 RESULTS 11.1 DATA SETS ANALYSED 11.2 DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS Table XX Demographics of the Study Patients Group A (N=) Gender Male Female Age (years) n Mean Min Max Height (m) n Mean Min Max Weight (kg) n Mean Min Max BMI (kg/m2) n Mean Min Max Group B (N=) See appendix XX for by-patient tabular listings of demographic details. 11.3 MEASUREMENTS OF TREATMENT COMPLIANCE 11.4 STUDY DURATION Clinical Study Report Template Page 19 of 22 11.5 IMMUNOGENECITY RESULTS AND TABULATIONS OF PATIENT DATA 11.5.1 ANALYSIS OF IMMUNOGENECITY 11.5.2 STATISTICAL/ANALYTICAL ISSUES 11.5.2.1 HANDLING OF DROPOUTS OR MISSING DATA How if any dropouts were handled- why they dropped out, how long they were in the study for. Analysis of a pattern for patient drop out rates, determining factor, common variant. Missing data, incomplete CRF’s, how this is handled, and why this took place. 11.5.3 TABULATION OF INDIVIDUAL RESPONSE DATA 11.5.4 VACCINE DOSE AND RELATIONSHIP TO RESPONSE 11.5.5 BY-PATIENT DISPLAYS 11.5.6 IMMUNOGENECITY CONCLUSIONS 12 SAFETY EVALUATION 12.1 EXTENT OF EXPOSURE 12.2 ADVERSE EVENTS (AE’s) 12.2.1 BRIEF SUMMARY OF ADVERSE EVENTS 12.2.2 TREATMENT EMERGENT ADVERSE EVENTS 12.2.3 TREATMENT RELATED ADVERSE EVENTS 12.2.4 IMMUNISATION TOLERANCE Clinical Study Report Template Page 20 of 22 12.3 SERIOUS ADVERSE EVENTS AND OTHER SIGNIFICANT ADVERSE EVENTS 12.4 DEATHS 12.5 CLINICAL LABORATORY EVALUATION 12.5.1 EVALUATION OF EACH LABORATORY PARAMETER 12.6 VITAL SIGNS, PHYSICAL FINDINGS AND OTHER OBSERVATIONS RELATED TO SAFETY 12.7 CONCOMITTANT MEDICATION USE 12.8 SAFETY CONCLUSIONS 13 DISCUSSION AND OVERALL CONCLUSIONS 14 TABLES, FIGURES AND GRAPHS 15 REFERENCES 16 APPENDICES 16.1 STUDY INFORMATION 16.1.1 Protocol and Protocol Amendments 16.1.2 Case Report Form 16.1.3 Ethics Committees and Subject Information 16.1.4 Regulatory Approval 16.1.5 Investigators and Study Personnel Clinical Study Report Template Page 21 of 22 16.1.6 Sponsor and Investigator Signatures 16.1.7 Randomisation Code 16.1.8 Study Drugs 16.1.9 Audit Certificate 16.1.10 Statistical Analysis Plan 16.1.11 Laboratory quality assurance 16.1.12 Publications based on the study 16.1.13 Publications referenced in the report 16.2 PATIENT DATA LISTINGS 16.3 CASE REPORT FORMS 16.3.1 CRFs for deaths, other serious adverse events and withdrawals for AE 16.3.2 Other CRFs submitted Clinical Study Report Template Page 22 of 22