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Statistical Analysis Plan NCT03124108 Statistical Analysis Plan Document Type: Template Document ID: 03.007A.03 Issue Date: 02 MAY 2016 Effective Date: 30 MAY 2016 Sponsor Name: Genfit Protocol Number and Title: GFT505B-216-1 A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of Elafibranor at doses of 80 mg and 120 mg After 12 Weeks of Treatment in Patients With Primary Biliary Cholangitis and Inadequate Response to Ursodeoxycholic Acid Protocol Version and Date: FINAL V3.0 04 December 2017 <Protocol Amendment numbers and dates> Project 1009105 Code: Author(s): SAP Version: 2.0 SAP Version Date: 11 November 2018 Notice of Confidential and Proprietary Information: The information contained in this document is confidential belonging to Genfit. Acceptance of this document constitutes agreement by the recipient that no information contained herein will be published or disclosed without prior written authorization from an official of Genfit. However, this document may be disclosed to appropriate Institutional Review Board and Ethics Committees or duly authorized representatives of a national regulatory authority under the condition that they are requested to keep it confidential. In the event of an actual or suspected breach of this obligation, should be notified promptly. This document is proprietary and confidential to 03.007A.03 Page 1 of 70 Statistical Analysis Plan GENFIT Protocol # GFT505B-216-1 Version 2.0 Revision History Version # Date Document Owner Revision Summary (dd-mmm-yyyy) 0.2 31-May-2017 Initial Release Version 0.3 14-June-2017 Updated Version 0.4 31-JUL-2018 Updated Version considered final 1.0 01-Aug-2018 Merged secondary endpoints into one table Modification on statistical analyses concerning 1.1 05-Nov-2018 some laboratory parameters Final modifications made after dry run and BDRM. 1.2 20-Nov-2018 Addition of one table Clarification of EndPoint value definition 2.0 21NOV2018 Lysophosphatidic acid replaced by autotaxin Updates to be consistent throughout SAP and shells This document is proprietary and confidential to . 03.007A.03 Page 2 of 70 Statistical Analysis Plan GENFIT Protocol # GFT505B-216-1 Version 2.0 This document is proprietary and confidential to 03.007A.03 Page 4 of 70 Statistical Analysis Plan GENFIT Protocol # GFT505B-216-1 Version 2.0 TABLE OF CONTENTS Contents 1. GLOSSARY OF ABBREVIATIONS .............................................................. 9 2. PURPOSE ...................................................................................... 13 2.1. Responsibilities ....................................................................................... 13 2.2. Timings of Analyzes .................................................................................. 13 3. STUDY OBJECTIVES .......................................................................... 14 3.1. Primary Objective .................................................................................... 14 3.2. Secondary Objective(s) ............................................................................. 14 3.3. Brief Description ...................................................................................... 15 3.4. Subject Selection ..................................................................................... 15 3.4.1. Inclusion Criteria ................................................................................ 15 3.4.2. Exclusion Criteria ............................................................................... 16 3.5. Determination of Sample Size ..................................................................... 19 3.6. Treatment Assignment & Blinding ................................................................ 19 3.7. Administration of Study Medication .............................................................. 20 3.8. Study Procedures and Flowchart ................................................................. 20 4. ENDPOINTS .................................................................................... 25 4.1. Primary Efficacy Endpoint .......................................................................... 25 4.2. Secondary Efficacy Endpoints ..................................................................... 25 4.3. Safety Endpoints ...................................................................................... 26 5. ANALYSIS SETS ............................................................................... 27 5.1. Enrolled Set ............................................................................................ 27 This document is proprietary and confidential to 03.007A.03 Page 5 of 70 Statistical Analysis Plan GENFIT Protocol # GFT505B-216-1 Version 2.0 5.2. Safety Set .............................................................................................. 27 5.3. Intent-to-Treat ........................................................................................ 27 5.4. Per Protocol Set ...................................................................................... 27 5.5. Protocol Deviations .................................................................................. 27 6. GENERAL ASPECTS FOR STATISTICAL ANALYSIS ....................................... 29 6.1. General Methods ...................................................................................... 29 6.2. Key Definitions ........................................................................................ 29 6.3. Missing Data ............................................................................................ 31 6.4. Visit Windows.......................................................................................... 31 6.5. Pooling of CentREs ................................................................................... 32 6.6. Subgroups .............................................................................................. 32 7. DEMOGRAPHIC, OTHER BASELINE CHARACTERISTICS AND MEDICATION ........... 33 7.1. Subject Disposition and Withdrawals ............................................................ 33 7.2. Demographic and Other Baseline Characteristics ............................................. 33 7.3. Medical History and Concomitant Diseases ..................................................... 34 7.4. OTHER BASELINE CHARACTERISTICS .............................................................. 35 7.5. Medication ............................................................................................. 35 7.5.1. Prior Medication ................................................................................ 36 7.5.2. Concomitant Medication ....................................................................... 36 8. EFFICACY ...................................................................................... 38 8.1. Primary Efficacy Endpoint and Analysis ......................................................... 38 8.2. Secondary Efficacy Endpoints and Analyzes .................................................... 40 8.2.1. Response rate based on two composite endpoints ....................................... 41 8.2.2. Response rate according to PBC risk scores ................................................ 42 8.2.3. Response rate according to normalized laboratory values .............................. 42 8.2.4. Response rate according to reduction in ALP levels ...................................... 43 8.2.5. Change from baseline .......................................................................... 43 This document is proprietary and confidential to 03.007A.03 Page 6 of 70 Statistical Analysis Plan GENFIT Protocol # GFT505B-216-1 Version 2.0 9. SAFETY ........................................................................................ 46 9.1. EXTENT OF EXPOSURE ............................................................................... 46 9.2. Treatment Compliance .............................................................................. 46 9.3. Adverse Events / Adverse Drug Reactions ...................................................... 46 9.4. Laboratory Evaluations .............................................................................. 48 9.5. Vital Signs .............................................................................................. 50 9.6. ECG ...................................................................................................... 51 9.7. Physical Examination ................................................................................ 51 9.8. StaNdard Diet and Exercise Recommendations ................................................ 51 10. CHANGE FROM ANALYSIS PLANNED IN PROTOCOL ..................................... 52 11. REFERENCE LIST ............................................................................. 53 12. PROGRAMMING CONSIDERATIONS ......................................................... 54 12.1. General Considerations ............................................................................. 54 12.2. Table, Listing, and Figure Format ................................................................ 54 12.2.1. General ........................................................................................... 54 12.2.2. Headers ........................................................................................... 54 12.2.3. Display Titles .................................................................................... 55 12.2.4. Column Headers ................................................................................
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