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Statistical Analysis Plan for Primary Analysis, and Final Analysis

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Statistical Analysis Plan for Primary Analysis, and Final Analysis NCT02993250 Janssen Pharmaceutical K.K. * Statistical Analysis Plan for Primary Analysis, and Final Analysis A Phase 2a, Multicenter, Open-label Study to Investigate the Safety, Pharmacokinetics, and Efficacy of Combination Treatment of AL-335, Odalasvir, and Simeprevir in Japanese Subjects With Chronic Hepatitis C Genotype 1 or 2 Virus Infection, With or Without Compensated Cirrhosis who are Direct-acting Antiviral Treatment-naïve Protocol 64294178HPC2003; Phase 2a AL-335, Odalasvir, TMC435(simeprevir) *This study is being conducted by Janssen Pharmaceutical K.K. in Japan. The term “sponsor” is used throughout the protocol to represent Janssen Pharmaceutical K.K. Status: Approved Date: 8 June 2018 Prepared by: Janssen Pharmaceutical K.K. Document No.: EDMS-ERI-164033457 Compliance: The study described in this report was performed according to the principles of Good Clinical Practice (GCP). Confidentiality Statement The information in this document contains trade secrets and commercial information that are privileged or confidential and may not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed by them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as privileged or confidential. 1 Approved, Date: 8 June 2018 NCT02993250 AL-335, Odalasvir, TMC435(simeprevir) Statistical Analysis Plan 64294178HPC2003 TABLE OF CONTENTS TABLE OF CONTENTS ............................................................................................................................... 2 ABBREVIATIONS ........................................................................................................................................ 4 1. INTRODUCTION .................................................................................................................................. 5 1.1. Trial Objectives ................................................................................................................................ 5 1.2. Trial Design ...................................................................................................................................... 6 1.2.1. Endpoints ...................................................................................................................................... 6 1.3. Statistical Hypotheses for Trial Objectives ....................................................................................... 7 1.4. Sample Size Justification ................................................................................................................. 7 1.5. Randomization and Blinding ............................................................................................................ 7 2. GENERAL ANALYSIS DEFINITIONS ................................................................................................ 7 2.1. Visit Windows and Phase Definition ................................................................................................ 7 2.2. Pooling Algorithm for Analysis Centers .......................................................................................... 10 2.3. Analysis Sets .................................................................................................................................. 10 2.4. Definition of Subgroups .................................................................................................................. 10 3. SUBJECT INFORMATION ................................................................................................................ 10 3.1. Demographics and Baseline Characteristics ................................................................................. 10 3.2. Disposition Information ................................................................................................................... 11 3.3. Treatment Adherence .................................................................................................................... 12 3.4. Extent of Exposure ......................................................................................................................... 12 3.5. Protocol Deviations ........................................................................................................................ 12 3.6. Prior and Concomitant Medications ............................................................................................... 12 3.7. Medical History ............................................................................................................................... 13 4. EFFICACY ......................................................................................................................................... 13 4.1. Level of Significance ...................................................................................................................... 13 4.2. Data Handling Rules ...................................................................................................................... 13 4.3. Efficacy Endpoints .......................................................................................................................... 13 4.3.1. Definitions ................................................................................................................................... 14 4.3.2. Analysis Methods ........................................................................................................................ 17 4.3.3. Treatment Stopping Rules .......................................................................................................... 18 5. VIROLOGY ........................................................................................................................................ 19 5.1. Virology Assessments .................................................................................................................... 19 5.1.1. Viral strain typing ........................................................................................................................ 19 5.1.2. Viral sequencing ......................................................................................................................... 19 5.2. Virology Definitions ........................................................................................................................ 19 5.3. Virology Time Points and Samples ................................................................................................ 20 5.4. Virology Analyses ........................................................................................................................... 20 5.4.1. HCV geno/subtype analyses ...................................................................................................... 20 5.4.2. Resistance analyses ................................................................................................................... 21 5.4.2.1. Baseline ................................................................................................................................... 21 5.4.2.2. Post-Baseline ........................................................................................................................... 21 5.4.2.3. Over the Study Period ............................................................................................................. 21 6. SAFETY ............................................................................................................................................. 21 6.1. Adverse Events .............................................................................................................................. 21 6.1.1. Definitions ................................................................................................................................... 21 6.1.2. Analysis Methods ........................................................................................................................ 22 6.2. Clinical Laboratory Tests................................................................................................................ 23 6.2.1. Definitions ................................................................................................................................... 24 6.2.2. Analysis Methods ........................................................................................................................ 24 6.3. Vital Signs and Physical Examination Findings ............................................................................. 25 2 Approved, Date: 8 June 2018 NCT02993250 AL-335, Odalasvir, TMC435(simeprevir) Statistical Analysis Plan 64294178HPC2003 6.3.1. Definitions ................................................................................................................................... 25 6.3.2. Analysis Methods ........................................................................................................................ 25 6.4. Electrocardiogram .......................................................................................................................... 26 6.4.1. Definitions ................................................................................................................................... 26 6.4.2. Analysis Methods .......................................................................................................................
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