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Protocol H8A-MC-LZBE a 24-Month, Phase 3, Multicenter, Placebo

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Protocol H8A-MC-LZBE a 24-Month, Phase 3, Multicenter, Placebo Protocol H8A-MC-LZBE A 24-Month, Phase 3, Multicenter, Placebo-Controlled Study of Efficacy and Safety of Solanezumab versus Placebo in Prodromal Alzheimer’s Disease NCT02760602 Approval Date: 28-Mar-2016 H8A-MC-LZBE Clinical Protocol Page 1 Protocol H8A-MC-LZBE A 24-Month, Phase 3, Multicenter, Placebo-Controlled Study of Efficacy and Safety of Solanezumab versus Placebo in Prodromal Alzheimer’s Disease Confidential Information The information contained in this document is confidential and is intended for the use of clinical investigators. It is the property of Eli Lilly and Company or its subsidiaries and should not be copied by or distributed to persons not involved in the clinical investigation of solanezumab (LY2062430), unless such persons are bound by a confidentiality agreement with Eli Lilly and Company or its subsidiaries. Note to Regulatory Authorities: This document may contain protected personal data and/or commercially confidential information exempt from public disclosure. Eli Lilly and Company requests consultation regarding release/redaction prior to any public release. In the United States, this document is subject to Freedom of Information Act (FOIA) Exemption 4 and may not be reproduced or otherwise disseminated without the written approval of Eli Lilly and Company or its subsidiaries. Solanezumab (LY2062430) Study H8A-MC-LZBE is a multicenter, randomized, double-blind, placebo-controlled, Phase 3 study comparing solanezumab with placebo for 24 months in approximately 2450 patients with prodromal Alzheimer’s disease (AD). Eli Lilly and Company Indianapolis, Indiana USA 46285 Protocol Electronically Signed and Approved by Lilly on date provided below. Approval Date: 28-Mar-2016 GMT LY2062430 H8A-MC-LZBE Clinical Protocol Page 2 Table of Contents Section Page 1. Protocol Synopsis................................................................................................................8 2. Schedule of Activities .......................................................................................................12 3. Introduction ......................................................................................................................20 4. Objectives and Endpoints..................................................................................................22 5. Study Design.....................................................................................................................24 5.1. Overview of Study Design ...........................................................................................24 5.2. End of Double-Blind Treatment Period and End of Trial..............................................24 5.3. Scientific Rationale for Study Design...........................................................................24 5.4. Justification for Dose ...................................................................................................25 5.5. Benefit/Risk Assessment ..............................................................................................25 6. Study Population...............................................................................................................26 6.1. Inclusion Criteria..........................................................................................................26 6.2. Exclusion Criteria ........................................................................................................27 6.3. Screen Failures.............................................................................................................29 6.4. Lifestyle and/or Dietary Requirements .........................................................................29 7. Treatment..........................................................................................................................30 7.1. Treatments Administered .............................................................................................30 7.2. Method of Treatment Assignment ................................................................................30 7.2.1. Selection and Timing of Doses.............................................................................30 7.3. Blinding .......................................................................................................................30 7.4. Packaging and Labeling ...............................................................................................31 7.5. Preparation/Handling/Storage.......................................................................................31 7.6. Dose Modification........................................................................................................31 7.7. Treatment Compliance .................................................................................................31 7.8. Concomitant Therapy...................................................................................................32 7.9. Treatment after Study Completion................................................................................32 8. Discontinuation Criteria ....................................................................................................33 8.1. Discontinuation of Inadvertently Enrolled Patients.......................................................33 8.2. Discontinuation from the Study....................................................................................33 8.3. Patients Lost to Follow-Up...........................................................................................35 9. Study Assessments and Procedures ...................................................................................36 9.1. Efficacy Assessments...................................................................................................36 9.1.1. Primary Efficacy Assessments .............................................................................36 9.1.2. Secondary Efficacy Assessments..........................................................................36 LY2062430 H8A-MC-LZBE Clinical Protocol Page 3 9.1.3. Appropriateness of Assessments ..........................................................................39 9.2. Safety Evaluations........................................................................................................40 9.2.1. Adverse Events ....................................................................................................40 9.2.2. Serious Adverse Events........................................................................................41 9.2.2.1. Suspected Unexpected Serious Adverse Reactions..........................................42 9.2.2.2. Adverse Events of Special Interest..................................................................42 9.2.3. Complaint Handling.............................................................................................42 9.3. Other Safety Assessments ............................................................................................42 9.3.1. Physical Examinations and Neurologic Examination............................................42 9.3.2. Electrocardiograms ..............................................................................................43 9.3.3. Vital Signs ...........................................................................................................43 9.3.4. Body Weight and Height......................................................................................43 9.3.5. Laboratory Tests ..................................................................................................44 9.3.6. Magnetic Resonance Imaging...............................................................................44 9.3.7. Columbia Suicide Severity Rating Scale (Adult Version) .....................................44 9.3.8. Safety Monitoring ................................................................................................45 9.4. Sample Collection and Testing .....................................................................................45 9.4.1. Samples for Study Qualification and Health Monitoring.......................................45 9.4.2. CSF Aβ and Tau Proteins and Solanezumab.........................................................45 9.4.2.1. Timing of CSF Sampling................................................................................46 9.4.2.2. CSF Collection Procedures.............................................................................46 9.4.3. Plasma Samples for Assessment of As and Solanezumab ...................................46 9.4.3.1. Timing of Plasma Sampling............................................................................46 9.4.3.2. Plasma Collection Procedures.........................................................................46 9.4.4. Serum Samples for Anti-Solanezumab Immunogenicity.......................................47 9.4.4.1. Timing of Blood Sampling .............................................................................47 9.4.4.2. Blood Collection Procedures ..........................................................................47 9.4.5. Apolipoprotein E Genotyping...............................................................................48 9.4.6. Samples for Biomarker Research..........................................................................48 9.4.6.1. Pharmacogenetic Samples ..............................................................................48 9.4.6.2. Biomarker Storage Samples............................................................................48
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