Common Protocol Template (CPT) May 2017 Release Highlights

Table of Contents Section Slide(s) Summary of CPT Releases 3 Installation Instructions for May 2017 Release 4 CPT Release and Version Identification Conventions 5 What’s Included in the May 2017 Release 6 May 2017 Release – Content Updates 7 – 22 May 2017 Release – Technology Improvements 23 - 26

Summary of CPT Releases Intended Audience Template versions included Release Number Release Date Member Companies Public Basic Word Tech-Enabled 1.0 August 2015  2.0 December 2015 3.0 June 2016 Release Number no longer being assigned May 2017

Installation Instructions for the May 2017 Release For new users (no prior CPT edition installed) Please follow the CPT Installation Instructions document. http://www.transceleratebiopharmainc.com/assets/common-protocol-template/ For users updating to May 2017 Release (prior CPT edition already installed) Please uninstall the previous version and then follow the CPT Installation Instructions document. Go to Control Panel>Programs and Features> and select the below 2 files to uninstall: CPT Intelligent Content Management CPT Library Management Add-In

CPT Release and Version Identification Conventions Releases Beginning with the May 2017 Release, releases are referenced by year and month date (e.g., the October 2018 release). A list of all files and their version number is compiled and published with the release. Versions Versions are referenced by a 3 digit number at the end of the file name. EXAMPLE FILE NAME: CPT_CoreBWE_V004.dotx Each file is numbered independently. Files are versioned only as a result of revision. Note: There is a one time exception to move to the new version numbering convention in the May 2017 release. A summary of changes from previous version is provided for every version of every file released. There is no distinction made between major and minor revisions.

What’s Included in the May 2017 Release? Content Updates Alignment of CPT with NIH-FDA Protocol Template NIH = National Institutes of Health; FDA = Food and Drug Administration Addition of designated fields to facilitate Trial Registration to CT.gov Contraception language Miscellaneous updates - Core Template Existing Libraries Participant: Healthy, Patient Therapeutic Area: Asthma, Diabetes New Participant Library: Pediatrics New Therapeutic Area Libraries: Alzheimer’s Disease, QT Technology Improvements Improve instructional text pane Improve library selection interface Improve example text use/formatting NOTE: Comparison documents are available to view specific updates for CPT Core and all libraries being revised.

May 2017 Release - Content Updates Alignment of CPT with NIH-FDA Protocol Template Rationale/Goal Mutual desire to harmonize templates (CPT and NIH-FDA Protocol Template) Acknowledged different audiences: NIH-FDA Protocol Template targeted at single- center and investigator led studies; CPT targeted at global multi-center studies. Harmonizing templates will drive harmonization in resulting protocols regardless of template used Alignment on all Level 1 headings, and most Level 2 headings Both templates (CPT and NIH-FDA Protocol Template) to be maintained, modifications to each to achieve greatest harmonization Updates Included Revised order/placement of several sections Where different Level 2 headings are required, they are placed after the common Level 2 headings. Combined several sections Harmonized terminology where applicable

May 2017 Release - Content Updates Alignment of CPT with NIH-FDA Protocol Template Updates Included – Throughout the template CPT Release 3.1 (Current Release) Aligned CPT and NIH-FDA Protocol Template Headings (May 2017 Release) Use of the word “treatment” now referred to as “intervention”

May 2017 Release - Content Updates Alignment of CPT with NIH-FDA Protocol Template Updates Included – Section Numbers/Titles/Sequence CPT Release 3.1 (Current Release) Aligned CPT and NIH-FDA Protocol Template Headings (May 2017 Release) Title Page Signature Page Protocol Amendment Summary of Changes Table Table of Contents 1 Synopsis 2 Schedule of Activities (SoA) 1 Protocol Summary 1.1 Synopsis 1.2 Schema 1.3 Schedule of Activities (SoA) 3 Introduction 3.1 Study Rationale 3.2 Background 3.3 Benefit/Risk Assessment 2 Introduction 2.1 Study Rationale 2.2 Background 2.3 Benefit/Risk Assessment 4 Objectives and Endpoints 3 Objectives and Endpoints

May 2017 Release - Content Updates Alignment of CPT with NIH-FDA Protocol Template Updates Included – Section Numbers/Titles/Sequence CPT Release 3.1 (Current Release) Aligned CPT and NIH-FDA Protocol Template Headings (May 2017 Release) 5 Study Design 5.1 Overall Design 5.2 Participant and Study Completion 5.3 End of Study Definition 5.4 Scientific Rationale for Study Design 5.5 Justification for Dose 4 Study Design 4.1 Overall Design 4.2 Scientific Rationale for Study Design 4.3 Justification for Dose 4.4 End of Study Definition 6 Study Population 6.1 Inclusion Criteria 6.2 Exclusion Criteria 6.3 Lifestyle Restrictions 6.4 Screen Failures 5 Study Population 5.1 Inclusion Criteria 5.2 Exclusion Criteria CPT 5.3 Lifestyle Considerations CPT 5.4 Screen Failures NIH 5.3 NIH Recruitment

May 2017 Release - Content Updates Alignment of CPT with NIH-FDA Protocol Template Updates Included – Section Numbers/Titles/Sequence CPT Release 3.1 (Current Release) Aligned CPT and NIH-FDA Protocol Template Headings (May 2017 Release) 7 Treatments 7.1 Study Treatment Administered 7.2 Dose Modification 7.3 Method of Treatment Assignment 7.4 Blinding 7.5 Preparation/Handling/Storage/Accountability 7.6 Treatment Compliance 7.7 Concomitant Therapy 7.8 Treatment after the End of the Study 6 Study Intervention 6.1 Study Intervention(s) Administered 6.2 Preparation/Handling/Storage/Accountability 6.3 Measures to Minimize Bias: Randomization and Blinding 6.4 Study Intervention Compliance 6.5 Concomitant Therapy CPT 6.6 Dose Modification CPT 6.7 Intervention after the End of the Study

May 2017 Release - Content Updates Alignment of CPT with NIH-FDA Protocol Template Updates Included – Section Numbers/Titles/Sequence CPT Release 3.1 (Current Release) Aligned CPT and NIH-FDA Protocol Template Headings (May 2017 Release) 8 Discontinuation/Withdrawal Criteria 8.1 Discontinuation of Study Treatment 8.2 Withdrawal from the Study 8.3 Lost to Follow Up 7 Discontinuation of Study Intervention and Participant Discontinuation/Withdrawal 7.1 Discontinuation of Study Intervention 7.2 Participant Discontinuation/Withdrawal from the Study 7.3 Lost to Follow Up

May 2017 Release - Content Updates Alignment of CPT with NIH-FDA Protocol Template Updates Included – Section Numbers/Titles/Sequence CPT Release 3.1 (Current Release) Aligned CPT and NIH-FDA Protocol Template Headings (May 2017 Release) 9 Study Assessments and Procedures 9.1 Efficacy Assessments 9.2 Adverse Events 9.3 Treatment of Overdose 9.4 Safety Assessments 9.5 Pharmacokinetics 9.6 Pharmacodynamics 9.7 [Genetics] 9.8 Biomarkers 9.9 [Health Economics] OR [Medical Resource Utilization and Health Economics] 8 Study Assessments and Procedures 8.1 Efficacy Assessments 8.2 Safety Assessments 8.3 Adverse Events and Serious Adverse Events CPT 8.4 Treatment of Overdose CPT 8.5 Pharmacokinetics CPT 8.6 Pharmacodynamics CPT 8.7 [Genetics] CPT 8.8 Biomarkers CPT 8.9 [Health Economics] OR [Medical Resource Utilization and Health Economics] NIH 8.4 Reporting of Unexpected Problems NIH 8.5 Handling of Specimen

May 2017 Release - Content Updates Alignment of CPT with NIH-FDA Protocol Template Updates Included – Section Numbers/Titles/Sequence CPT Release 3.1 (Current Release) Aligned CPT and NIH-FDA Protocol Template Headings (May 2017 Release) 10 Statistical Considerations 9.1 Sample Size Determination 9.2 Populations for Analyses 9.3 Statistical Analyses 9 Statistical Considerations 9.1 Statistical Hypotheses 9.2 Sample Size Determination 9.3 Populations for Analyses 9.4 Statistical Analyses 9.5 Interim Analysis

May 2017 Release - Content Updates Alignment of CPT with NIH-FDA Protocol Template Updates Included – Section Numbers/Titles/Sequence CPT Release 3.1 (Current Release) Aligned CPT and NIH-FDA Protocol Template Headings (May 2017 Release) 11 References   12 Appendices Appendix 1: Abbreviations and Trademarks Appendix 2: Clinical Laboratory Tests Appendix 3: Study Governance Considerations Appendix 4: Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-up, and Reporting Appendix 5: Contraceptive Guidance and Collection of Pregnancy Information Appendix 6: Genetics Appendix 7: Liver Safety: Suggested Actions and Follow-up Assessments [and Study Treatment Rechallenge Guidelines] Appendix 8: Medical Device Incidents: Definition and Procedures for Recording, Evaluating, Follow-up, and Reporting Appendix 9: Country-specific requirements Appendix 10: Protocol Amendment History 10 Supporting Documentation and Operational Considerations 10.1 Appendix 1: Regulatory, Ethical, and Study Oversight Considerations CPT 10.2 Appendix 2: Clinical Laboratory Tests CPT 10.3 Appendix 3: Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-up, and Reporting CPT 10.4 Appendix 4: Contraceptive Guidance and Collection of Pregnancy Information CPT 10.5 Appendix 5: Genetics CPT 10.6 Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments [and Study Intervention Rechallenge Guidelines] CPT 10.7 Appendix 7: Medical Device Incidents: Definition and Procedures for Recording, Evaluating, Follow-up, and Reporting CPT 10.8 Appendix 8: Country-specific requirements CPT 10.9 Appendix 9: Abbreviations CPT 10.10 Appendix 10: Protocol Amendment History

May 2017 Release - Content Updates Addition of designated fields to facilitate Trial Registration to CT.gov Rationale/Goal Enable Registration of the Protocol – Trial Disclosure Form – original registration and updated once per amendment No impact for Operational elements (e.g. #sites, start date, # enrolled) or Results Reporting aspects of Trial Registration Ability to export registration data directly from the protocol Updates Included CPT captures protocol related data for disclosure fields per CDISC CTR standards Updated variable names, new variables Character limits on variables where required by CT.gov Export of all captured variables in CDISC CTR-XML Additional disclosure-related instructional text

May 2017 Release - Content Updates Contraception Language Rationale/Goal To align the requirements with current guidance on contraception in clinical trials. Updates Included May 2017 Section # and Name Description of Change from CPT Release 3.1 Brief Rationale 10.4 Appendix 4: Contraceptive Guidance and Collection of Pregnancy – WOCBP (Women of Childbearing Potential) Required use of contraception for females on HRT (hormone replacement therapy) or whose menopausal status is in doubt specifies non-estrogen hormonal contraception (previously hormonal contraception). For women already receiving hormonal replacement with estrogen, additional estrogen-containing hormonal contraception may increase risks from high levels. 10.4 Appendix 4: Contraceptive Guidance and Collection of Pregnancy – Male Participants Changed placement of requirement for male participant to refrain from donating sperm. To clarify that this requirement applies to all men rather than only those with female partners of childbearing potential.

May 2017 Release - Content Updates Miscellaneous Updates - Core Template Updates Included May 2017 Section # and Name Description of Change from CPT Release 3.1 Brief Rationale Instructional Text (red); Example Text(green); Variable Text (blue) Various updates and additions throughout template To aid in authoring the protocol 1.1 Synopsis – Objectives and Endpoints Tertiary/Exploratory objectives and endpoints deleted from Synopsis (maintained in Section 3 of protocol) To remove text not commonly used 1.1 Synopsis – Number of Participants Deleted former section “ 5.2 Participant and Study Completion” including statements about numbers of participants screened and randomized Number of Participants is now placed in section 9.2 Sample Size Determination, and also highlighted in 1.1 Synopsis 1.1 Synopsis – Data Monitoring Committee Section added to allow author to specify Yes/No regarding use of a Data Monitoring Committee To provide an indicator of this study design element, and easy retrieval for reporting to clinical trial registries

May 2017 Release - Content Updates Miscellaneous Updates – Core Template Updates Included May 2017 Section # and Name Description of Change from CPT Release 3.1 Brief Rationale 1.2 Schema Separate section added for study schema To provide a common, titled location 7.3 Lost To Follow Up – last bullet regarding unreachable participants Deleted phrase “with a primary reason of lost to follow up” To remove common text 8. Study Assessments and Procedures Added common text to refer the reader to SoA for information about study procedures and timing To provide cross-reference to information within the protocol 9.5.1 Data Monitoring Committee (DMC) Added new Level 3 section

May 2017 Release - Content Updates Existing Libraries – Healthy, Patient, Asthma, Diabetes Updates Included May 2017 Section # and Name Description of Change from CPT Release 3.1 Brief Rationale Instructional Text (red); Example Text(green); Variable Text (blue) Various updates and additions throughout libraries To aid in authoring the protocol Use of the word “treatment” “Intervention” is now used throughout the libraries To facilitate use of common text across broader range of study types References to Level 1 and Level 2 headings in the template Updated to reference new Level 1 and Level 2 headings To facilitate alignment of library text to the core template sections Acronyms/Abbreviations Where missing, defined throughout the libraries To aid comprehension Patient Library – 5.2 Exclusion Criteria - #14 Update to liver/biliary disease exclusion To clarify

May 2017 Release - Content Updates Existing Libraries – Healthy, Patient, Asthma, Diabetes Updates Included May 2017 Section # and Name Description of Change from CPT Release 3.1 Brief Rationale Patient Library – 5.2 Exclusion Criteria - #24 Removed note regarding Hepatitis B core antibody (HBcAb) exclusion To clarify Patient Library – 5.2 Exclusion Criteria - #25 Added the word “only” to Hepatitis C antibody exclusion Patient Library – 5.2 Section 7.1 – Discontinuation of study Intervention; and Appendix 6 Added definitions for test name and other abbreviations

May 2017 Release - Content Updates New Therapeutic Area Libraries Rationale/Goal CDISC, C-Path and TransCelerate are championing the development of new standards for various therapeutic areas. As TAUGs are developed by CDISC and C-Path, the CPT strives to develop aligned therapeutic area libraries. Based on questionnaire responses from member companies, new therapeutic area libraries corresponding to the most votes were initially undertaken.

May 2017 Release – Technology Improvements Automate Disclosure for CT.gov Rationale/Goal The CPT Template shall support automation to export variables for CT.gov Updates Included The following variables will be exported in the export functionality that currently exists in CPT. Additional variables will be included in the Fall 2017 release. Protocol Title Protocol Number Short Title Sponsor Name Sponsor Legal Address Number of Participants Additional Reporting Information Data Monitoring Committee Inclusion Criteria: Age: Planned Minimum Age of Subjects Inclusion Criteria: Age: Planned Maximum Age of Subjects Inclusion Criteria: Sex: Sex of Participants Exclusion Criteria: All content Controls

May 2017 Release – Technology Improvements Improve Instructional Text Pane Rationale/Goal To improve functionality and ease of use of the right hand CPT Panel and Instructional Text Box. Updates Included The right hand CPT panel sections have been renamed to better represent their functionality (Libraries, Instructional Text, Additional Content). The right hand CPT Instructional Text box can now be popped out and the wording increased/decreased/bolded for easier view when authoring the CPT Template.

May 2017 Release – Technology Improvements Improve Library Selection Interface Rationale/Goal To assist authors when utilizing the template to select at least one of the two participant type libraries (e.g. Healthy Volunteer, or Patient) Updates Included When a user clicks on any content control in the template the Library Selection Window will open automatically for a user to select at least one of the participant type libraries (e.g. Healthy Volunteer, or Patient) Users can drag and drop a library or utilize arrow buttons The Participant Type library box now appears before Therapeutic Area

May 2017 Release – Technology Improvements Improve Example Text Use/Formatting Rationale/Goal To search through Example Text but find instances where Example Text may not have been formatted correctly. Updates Included Now when searching through Example Text, a prompt will appear letting users know if there is an instance where Example Text has been formatted incorrectly and will allow users to correct it.

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