Assessment of Safety, Tolerability and Efficacy of LY3002813 in Early Symptomatic Alzheimer's Disease
Phase: PHASE2
Conditions: Alzheimer Disease
Sponsor: Eli Lilly and Company

Protocol I5T-MC-AACG(d) 
 
Assessment of Safety, Tolerability, and Efficacy of LY3002813 in Early Symptomatic Alzheimer’s 
Disease 
 
 
NCT03367403 
 
Approval Date: 09-Oct-2018 
 
 

I5T-MC-AACG(d) Clinical Protocol
Page 1
LY3002813
Protocol I5T-MC-AACG(d)
Assessment of Safety, Tolerability, and Efficacy of 
LY3002813 in Early Symptomatic 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 
LY3002813, 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.
LY3002813
Multicenter, randomized, double-blind, placebo-controlled, Phase 2 study comparing up to 
1400 mg of LY3002813 with placebo over 76 weeks in approximately 250 patients with 
early symptomatic AD.
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Protocol Electronically Signed and Approved by Lilly:  30 August 2017  
Amendment (a) Electronically Signed and Approved by Lilly:  30 October 2017
Amendment (b) Electronically Signed and Approved by Lilly:  12 December 2017
Amendment (c) Electronically Signed and Approved by Lilly: 21 May 2018
Amendment (d) Electronically Signed and Approved by Lilly
on approval date provided below.
Approval Date: 09-Oct-2018 GMT
Please note that strikethroughs used in Appendix 7 do not indicate redacted content
but instead describe content removed during a protocol amendment.

I5T-MC-AACG(d) Clinical Protocol
Page 2
LY3002813
Table of Contents
Section
Page
Protocol I5T-MC-AACG(d) Assessment of Safety, Tolerability, and 
Efficacy of LY3002813 in Early Symptomatic Alzheimer’s Disease ...................................1
Table of Contents........................................................................................................................2
1.
Synopsis .............................................................................................................................9
2.
Schedule of Activities .......................................................................................................14
3.
Introduction ......................................................................................................................25
3.1.
Study Rationale............................................................................................................25
3.2.
Background..................................................................................................................26
3.2.1.
LY3002813 Nonclinical Studies...........................................................................26
3.2.2.
LY3002813 Phase 1 Studies.................................................................................27
3.3.
Benefit/Risk Assessment..............................................................................................28
3.3.1.
Benefit .................................................................................................................28
3.3.2.
Risks....................................................................................................................28
3.3.3.
Benefit/Risk Assessment Summary......................................................................30
4.
Objectives and Endpoints..................................................................................................32
5.
Study Design.....................................................................................................................34
5.1.
Overall Design .............................................................................................................34
5.1.1.
Screening Period (Visit 1) ....................................................................................36
5.1.1.1.
Screening Procedures .....................................................................................37
5.1.1.1.1.
Modified Hachinski Ischemic Scale (MHIS).............................................37
5.1.1.1.2.
Mini-Mental State Examination (MMSE) .................................................37
5.1.1.1.3.
CogState Brief Battery..............................................................................37
5.1.1.1.4.
Columbia Suicide Severity Rating Scale – Adult 
Version.....................................................................................................38
5.1.1.1.5.
Screening Positron Emission Tomography and 
Magnetic Resonance Imaging ...................................................................38
5.1.1.1.5.1.
Screening Flortaucipir F18 PET Scan..................................................38
5.1.1.1.5.2.
Screening MRI....................................................................................39
5.1.1.1.5.3.
Screening Florbetapir F18 PET Scan...................................................39
5.1.2.
Double-Blind Period (Visit 2 through Visit 21) ....................................................39
5.1.3.
Immunogenicity and Safety Follow-up Visits (Visits 801 
through 804) ........................................................................................................40
5.2.
Number of Participants.................................................................................................40
5.3.
End of Study Definition ...............................................................................................40
5.4.
Scientific Rationale for Study Design...........................................................................40

I5T-MC-AACG(d) Clinical Protocol
Page 3
LY3002813
5.5.
Justification for Dose ...................................................................................................41
6.
Study Population...............................................................................................................42
6.1.
Inclusion Criteria..........................................................................................................42
6.2.
Exclusion Criteria ........................................................................................................44
6.2.1.
Rationale for Exclusion of Certain Study Candidates ...........................................47
6.3.
Lifestyle Restrictions....................................................................................................47
6.4.
Screen Failures.............................................................................................................48
7.
Treatments........................................................................................................................49
7.1.
Treatments Administered .............................................................................................49
7.1.1.
Packaging and Labelling ......................................................................................49
7.1.1.1.
LY3002813 Packaging and Labelling .............................................................50
7.2.
Method of Treatment Assignment ................................................................................50
7.2.1.
Selection and Timing of Doses.............................................................................50
7.2.1.1.
LY3002813:  Selection and Timing of Doses..................................................50
7.3.
Blinding .......................................................................................................................51
7.4.
Dosage Modification....................................................................................................51
7.4.1.
LY3002813 Dosage Modification for ARIA-E.....................................................51
7.4.2.
LY3002813 Dosage Modification for ARIA-H ....................................................52
7.5.
Preparation/Handling/Storage/Accountability...............................................................52
7.6.
Treatment Compliance .................................................................................................53
7.6.1.
LY3002813 Treatment Compliance......................................................................53
7.7.
Concomitant Therapy...................................................................................................53
7.8.
Treatment after the End of the Study............................................................................54
7.8.1.
Treatment after Study Completion........................................................................54
8.
Discontinuation Criteria ....................................................................................................55
8.1.
Discontinuation from Study Treatment.........................................................................55
8.1.1.
Temporary Discontinuation from Study Treatment...............................................56
8.1.1.1.
Temporary Discontinuation from LY3002813 Study 
Treatment Due to ARIA-E..............................................................................56
8.1.1.2.
Temporary Discontinuation from LY3002813 Study 
Treatment for Reasons Other than ARIA-E.....................................................57
8.1.2.
Discontinuation of Inadvertently Enrolled Subjects..............................................57
8.2.
Discontinuation from the Study....................................................................................57
8.3.
Lost to Follow-Up........................................................................................................58
9.
Study Assessments and Procedures ...................................................................................59
9.1.
Efficacy Assessments...................................................................................................59
9.1.1.
Primary Efficacy Assessments .............................................................................59
9.1.2.
Secondary Efficacy Assessments..........................................................................60

I5T-MC-AACG(d) Clinical Protocol
Page 4
LY3002813
9.1.2.1.
Alzheimer’s Disease Assessment Scale—Cognitive 
subscale (ADAS-Cog13) ................................................................................60
9.1.2.2.
Alzheimer’s Disease Cooperative Study—Activities of 
Daily Living Inventory (ADCS-ADL) ............................................................60
9.1.2.3.
Clinical Dementia Rating Scale (CDR-SB).....................................................61
9.1.2.4.
Mini-Mental State Examination (MMSE) .......................................................61
9.1.3.
Biomarker Efficacy Measures (Double-Blind Period)...........................................61
9.1.4.
Appropriateness of Efficacy Assessments ............................................................61
9.2.
Adverse Events ............................................................................................................62
9.2.1.
Serious Adverse Events........................................................................................63
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions..........................................64
9.2.1.2.
Adverse Events of Special Interest..................................................................64
9.2.2.
Complaint Handling.............................................................................................64
9.3.
Treatment of Overdose.................................................................................................64
9.4.
Safety...........................................................................................................................65
9.4.1.
Physical and Neurological Examinations..............................................................65
9.4.2.
Electrocardiograms ..............................................................................................65
9.4.3.
Vital Signs ...........................................................................................................66
9.4.3.1.
Blood Pressure................................................................................................66
9.4.3.2.
Height, Weight, and Body Temperature..........................................................66
9.4.4.
Laboratory Tests ..................................................................................................67
9.4.5.
Immunogenicity Assessments ..............................................................................67
9.4.6.
Other Tests...........................................................................................................67
9.4.6.1.
Columbia Suicide Severity Rating Scale – Adult Version ...............................67
9.4.6.2.
Magnetic Resonance Imaging.........................................................................68
9.4.6.3.
Ophthalmological Examination.......................................................................68
9.4.6.4.
Dermatological Examination ..........................................................................69
9.4.7.
Safety Monitoring ................................................................................................70
9.4.7.1.
LY3002813 Hypersensitivity (Immediate and Non-
immediate), Including Infusion-Related Reactions..........................................70
9.4.7.1.1.
Premedication for Infusions ......................................................................70
9.4.7.1.2.
Management of Infusion Reactions...........................................................70
9.4.7.2.
LY3002813 Immunogenicity..........................................................................71
9.4.7.3.
Hepatic Safety Monitoring..............................................................................72
9.4.7.4.
Amyloid-Related Imaging Abnormalities (ARIA-E and 
ARIA-H) ........................................................................................................72
9.4.8.
Appropriateness of Safety Assessments................................................................73
9.5.
Pharmacokinetics .........................................................................................................73
9.6.
Pharmacodynamics ......................................................................................................74

I5T-MC-AACG(d) Clinical Protocol
Page 5
LY3002813
9.6.1.
Clearance of Amyloid Deposits............................................................................74
9.6.2.
Accumulation of Tau Deposits .............................................................................74
9.7.
Pharmacogenomics [OR] Genetics ...............................................................................75
9.7.1.
Apolipoprotein E Genotyping...............................................................................75
9.7.2.
Whole Blood Samples for Pharmacogenetic Research..........................................75
9.8.
Biomarkers...................................................................................................................75
9.9.
Medical Resource Utilization and Health Economics ...................................................76
10.
Statistical Considerations ..................................................................................................77
10.1. Sample Size Determination ..........................................................................................77
10.2. Populations for Analyses..............................................................................................77
10.3. Statistical Analyses ......................................................................................................78
10.3.1.
General Statistical Considerations ........................................................................78
10.3.1.1.
Handling of Missing Items for Scales .............................................................78
10.3.2.
Treatment Group Comparability...........................................................................79
10.3.2.1.
Subject Disposition.........................................................................................79
10.3.2.2.
Subject Characteristics....................................................................................79
10.3.2.3.
Prior and Concomitant Therapy......................................................................80
10.3.2.4.
Treatment Compliance....................................................................................80
10.3.3.
Efficacy Analyses ................................................................................................80
10.3.3.1.
Primary Analyses ...........................................................................................80
10.3.3.2.
Secondary Efficacy Analyses..........................................................................81
10.3.4.
Safety Analyses....................................................................................................81
10.3.4.1.
Adverse Events...............................................................................................81
10.3.4.2.
Vital Signs and Weight...................................................................................82
10.3.4.3.
Laboratory Analyses.......................................................................................82
10.3.4.4.
Electrocardiograms.........................................................................................83
10.3.4.5.
ARIA-E and ARIA-H.....................................................................................85
10.3.4.6.
Evaluation of Immunogenicity........................................................................85
10.3.4.7.
Suicidal Ideation and Behavior .......................................................................85
10.3.5.
Pharmacokinetic/Pharmacodynamic Analyses......................................................86
10.3.6.
Interim Analyses..................................................................................................86
11.
References ........................................................................................................................87
12.
Appendices .......................................................................................................................92

I5T-MC-AACG(d) Clinical Protocol
Page 6
LY3002813
List of Tables
Table
Page
Table AACG.4.1.Objectives and Endpoints...............................................................................32
Table AACG.7.1.Treatment Regimens, Double-Blind Period....................................................49
Table AACG.7.2.LY3002813 Dosage Modifications for First Occurrence of ARIA-E ..............52
Table AACG.10.1.
Criteria for Abnormal Vital Signs .......................................................82
Table AACG.10.2.
Criteria for Abnormal ECG Parameters...............................................84
Table AACG.10.3.
Criteria for Prolonged ECG QTcF Interval..........................................84

I5T-MC-AACG(d) Clinical Protocol
Page 7
LY3002813
List of Figures
Figure
Page
Figure AACG.5.1.
Illustration of study design for Clinical Protocol I5T-MC-
AACG. ..........................................................................................................35

I5T-MC-AACG(d) Clinical Protocol
Page 8
LY3002813
List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions........................................................................93
Appendix 2.
Clinical Laboratory Tests...............................................................................98
Appendix 3.
Study Governance Considerations................................................................100
Appendix 4.
Hepatic Monitoring Tests for Treatment-Emergent Abnormality..................105
Appendix 5.
Flortaucipir F18 Tau PET Imaging ..............................................................106
Appendix 6.
Florbetapir F18 Amyloid PET Imaging........................................................109
Appendix 7.
Protocol Amendment [I5T-MC-AACG(c)] Summary [Assessment of 
Safety, Tolerability, and Efficacy of LY3002813 in Early Symptomatic 
Alzheimer’s Disease]...................................................................................111

I5T-MC-AACG(d) Clinical Protocol
Page 9
LY3002813
1.
Synopsis
Title of Study:
Protocol I5T-MC-AACG(d).  Assessment of Safety, Tolerability, and Efficacy of LY3002813 in 
Early Symptomatic Alzheimer’s Disease.
Rationale:
LY3002813 is an antibody directed at the pyroglutamate modification of the third amino acid of 
amyloid beta (N3pG Aβ) epitope that is present only in brain amyloid plaques.  It is being 
studied for the treatment of Alzheimer’s disease (AD).  The mechanism of action of LY3002813 
is considered to be the targeting and removal of existing amyloid plaque, which is a key 
pathological hallmark of AD.  The clinical strategy for LY3002813 targets the N3pG Aβ specific 
to amyloid plaque in the population of early symptomatic AD patients with existing brain 
amyloid load, as measured using the amyloid plaque biomarker, florbetapir F18 positron 
emission tomography (PET) imaging.  This rationale is based on the amyloid hypothesis of AD,
which states that the production and deposition of Aβ is an early and necessary event in the 
pathogenesis of AD (Selkoe 2000).  Clinical support for this hypothesis comes from the 
demonstration that parenchymal Aβ levels are elevated before the appearance of symptoms of 
AD, and supported by genetic variants of AD that overproduce brain Aβ and genetic variants that 
protect against Aβ production (Jonsson et al. 2012; Fleisher et al. 2015).  Furthermore, early in 
the disease, the presence of brain amyloid appears to increase the risk of conversion from mild 
cognitive impairment (MCI) to AD dementia (Doraiswamy et al. 2012).  This suggests that 
enhanced clearance of Aβ will lead to slowing of AD progression.
Study I5T-MC-AACG (AACG) is a Phase 2, double-blind, placebo-controlled, study to evaluate
the safety and efficacy of N3pG antibody (LY3002813) in patients with early symptomatic AD 
(prodromal AD and mild dementia due to AD).  Study AACG will assess whether removal of 
existing amyloid plaque can slow the progression of disease as assessed by clinical measures and 
biomarkers of disease pathology and neurodegeneration over up to 72 weeks of treatment.
Multiple biomarkers of disease progress will also be evaluated.  The biomarker florbetapir F18 is 
a PET ligand that binds to fibrillar amyloid plaque.  This biomarker can provide a qualitative and 
quantitative measurement of brain plaque load in patients with prodromal AD or mild AD 
dementia.  The absence of significant florbetapir F18 signal on a visual read indicates that those 
patients clinically manifesting cognitive impairment have sparse to no amyloid plaques.  As 
such, implementation of florbetapir F18 will provide a screening tool for entry into the clinical 
trial and provide a confirmation of amyloid pathology.  Florbetapir F18 PET also provides 
quantitative assessment of fibrillar amyloid plaque in the brain and can assess amyloid plaque 
reductions from the brain by LY3002813.
Alzheimer’s disease progression is also associated with cerebral tauopathy, which will be 
assessed by flortaucipir F18 PET scans, a cortical marker of paired helical filaments.  Brain 
atrophy, as an indicator of neurodegeneration, will be assessed by volumetric resonance imaging 
(vMRI).

I5T-MC-AACG(d) Clinical Protocol
Page 10
LY3002813
The patient population for the clinical trial is selected to be AD patients with early symptomatic 
disease defined both clinically (prodromal to mild AD dementia) and by biomarkers (low to 
medium tau burden, plus amyloid plaque presence).  The 2018 NIA-AA draft AD research 
framework (Alzheimer’s Association 2017a) proposes that AD is defined by its underlying 
pathophysiologic processes which can be documented in vivo by biomarkers (such as tau and 
amyloid PET) or by post-mortem examination.  This framework will enable a more precise 
approach to therapeutic intervention trials where specific pathways can be targeted at specific 
points in the disease process and to the appropriate people (Alzheimer’s Association 2017b).  
Clinical-pathological correlations also strongly suggest that baseline imaging that allows staging 
on the basis of neurofibrillary tangles could substantially improve the power of clinical trials 
aimed at changing the rate of progression of the disease (Qian et al. 2017).  An early AD 
population defined clinically and pathologically is anticipated to be more homogeneous than 
populations defined without tau PET, and will be sufficiently early to respond to treatments prior 
to more advanced irreversible neuronal loss.

I5T-MC-AACG(d) Clinical Protocol
Page 11
LY3002813
Objective(s)/Endpoints:
Primary Objective
Primary Endpoint
To test the hypothesis that LY3002813 
administered for up to 72 weeks will decrease 
the cognitive and/or functional decline in 
patients with early symptomatic AD
Change in cognition and function as measured by the 
change in integrated Alzheimer’s Disease Rating Scale 
(iADRS) score from baseline to 18 months
Secondary Objectives
Secondary Endpoints
To assess the effect of LY3002813 vs. placebo 
on clinical progression in patients with early 
symptomatic AD
Change in cognition from baseline to 18 months as 
measured by:

the change in Alzheimer’s Disease Assessment 
Scale—Cognitive subscale (ADAS-Cog13) 
score

the change in Clinical Dementia Rating Scale 
Sum of Boxes (CDR-SB) score

the change in Mini-Mental State Examination 
(MMSE) score

the change in Alzheimer’s Disease Cooperative 
Study-instrumental Activities of Daily Living 
scale (ADCS-iADL) score 
To assess the effect of LY3002813 vs. placebo 
on brain amyloid deposition
Change in brain amyloid plaque deposition from 
baseline through 18 months as measured by florbetapir
F18 PET scan  
To assess the effect of LY3002813 vs. placebo 
on brain tau deposition
Change in brain tau deposition from baseline to 18 
months as measured by flortaucipir F18 PET scan  
To assess the effect of LY3002813 vs. placebo 
on brain volume measures
Change in volumetric MRI measures from baseline to 
18 months.
Safety Objective
Safety Endpoints
To evaluate safety and tolerability of 
LY3002813

Standard safety assessments:
o
spontaneously reported adverse events 
(AEs)
o
clinical laboratory tests
o
vital sign and body weight 
measurements
o
12-lead electrocardiograms (ECGs)
o
physical and neurological 
examinations

MRI (amyloid-related imaging abnormalities 
[ARIAs] and emergent radiological findings)

Columbia Suicide Severity Rating Scale
(C-SSRS)
Summary of Study Design:
Study AACG is a multicenter, randomized, double-blind, placebo-controlled, Phase 2 study of 
LY3002813 in subjects with early symptomatic AD.  The 133-week study includes a screening 

I5T-MC-AACG(d) Clinical Protocol
Page 12
LY3002813
period of up to 9 weeks, a treatment period of up to 72 weeks with final evaluations occurring 
4 weeks later at Week 76, and a 48-week immunogenicity and safety follow-up period.
Treatment Arms and Duration:
Patients will receive the following treatments for up to 72 weeks:

LY3002813:  intravenous LY3002813 (700 mg Q4WK for the first 3 doses, then 1400 
mg Q4WK) for up to 72 weeks or

Placebo:  intravenous placebo Q4WK for up to 72 weeks.
Approximate Number of Patients:
Screened – 1497
Randomized – 266
Statistical Analysis:
All efficacy analyses will follow the intent-to-treat (ITT) principle unless otherwise specified. 
An ITT analysis is an analysis of data by the groups to which subjects are assigned by random 
allocation, even if the subject does not take the assigned treatment, does not receive the correct 
treatment, or otherwise does not follow the protocol. Unless otherwise noted, all pairwise tests 
of treatment effects will be conducted at a 2-sided alpha level of 0.05; 2-sided confidence 
intervals (CIs) will be displayed with a 95% confidence level.
Efficacy:
The primary objective of this study is to test the hypothesis that intravenous infusion of 
LY3002813 will slow the cognitive and/or functional decline of AD as measured by the 
composite measure iADRS compared with placebo in patients with early symptomatic AD.  The 
change from baseline score on the iADRS at each scheduled postbaseline visit during the 
treatment period will be analyzed using an MMRM model, which includes the following terms:  
baseline score, pooled investigator, treatment, visit, treatment-by-visit interaction, baseline-by-
visit interaction, concomitant AChEI and/or memantine use at baseline (yes/no), and age at 
baseline.  The primary time point for treatment comparison will be at the end of the double blind 
treatment period (Week 76).  The treatment group contrast in least-squares mean progression and 
its associated p-value and 95% CI will be calculated for the treatment comparison of LY3002813 
vs. placebo.  In addition, Bayesian posterior probability of the active treatment arm being 
superior to placebo by at least a margin of interest (25% slowing of placebo progression) will 
also be calculated.
Change from baseline at each scheduled postbaseline visit during the treatment period in 
secondary efficacy outcomes, including ADAS-Cog13, ADCS-iADL, CDR-SB, and MMSE, will 
be analyzed using the same MMRM model described for the primary analysis.
Safety:
Safety will be assessed by summarizing and analyzing AEs, laboratory analytes, vital signs, MRI 
scans, ECGs, immunogenicity during the double-blind treatment period.

I5T-MC-AACG(d) Clinical Protocol
Page 13
LY3002813
Pharmacokinetics/Pharmacodynamics:
Compartmental modeling of LY3002813 PK data using nonlinear mixed effects modeling or 
other appropriate software may be explored, and population estimates for clearance and central 
volume of distribution may be reported.  Depending on the model selected, other PK parameters 
may also be reported.  Exploratory graphical analyses of the effect of dose level or demographic 
factors on PK parameters may be conducted.  If appropriate, data from other studies of 
LY3002813 may be used in this analysis.
Pharmacokinetic/pharmacodynamic (PK/PD) relationships between plasma LY3002813 
concentration and SUVr, cognitive endpoints, ARIA incidence rate or other markers of PD 
activity may be explored graphically.  The relationship between the presence of antibodies to 
LY3002813 and PK, PD, safety and/or efficacy may be assessed graphically.  If warranted, 
additional analysis may be explored to evaluate potential interactions for ADA, PD and other 
endpoints (PET scan, ARIA-E, etc.).  Additional modeling may be performed based on the 
results of the graphical analyses.

I5T-MC-AACG(d) Clinical Protocol
Page 14
LY3002813
2.
Schedule of Activities

I5T-MC-AACG(d) Clinical Protocol
Page 15
LY3002813
Schedule of Activities Protocol - I5T-MC-AACG Visit 1 (Screening Period)
Period:
Procedure
Visit No.:
V1
End of Week Relative to Study Medication Starta
Wk -9 through Wk -1
Tolerance Interval for Visit (days)a,b
63
PRELIMINARY SCREENING
Entry and Administrative 
Abbreviated (or full) Informed Consent – participant and study partnerc
X
  Patient number assigned via IWRS
X
  Demographics and habits
X
Entry Diagnostics 
  MMSEc,d,s
X
  CBBc
X
SCREENING
Full Informed Consent – participant and study partnerd
X
  Inclusion/exclusion review
X
  Physical/neurological examinatione
X
  Previous/concomitant medications
X
  Preexisting conditions 
X
Entry Diagnostics
  MHIS
X
Safety Assessments
   Vital signsf
X
   Height and weightg
X
   ECG in triplicateh
X
   C-SSRS/SHSF/SHFUi,j
X
Laboratory Specimens
  Human chorionic gonadotropin (HCG) (if applicable)k,l,m
Xb
  Clinical chemistry, hematology
Xb
  High sensitivity C-reactive protein
X
  HBsAgn
X
  HCV RNA PCRo
X
  Urinalysis
X
Screening PET Scans and MRI
   Flortaucipir F18 PET scanl,p
X
   MRIq
X
   Florbetapir F18 PET scanb,m,r
X

I5T-MC-AACG(d) Clinical Protocol
Page 16
LY3002813
Schedule of Activities, Protocol I5T-MC-AACG, Visit 1 (Screening Period) Abbreviations and Footnotes
Abbreviations:  A= amyloid ; CBB = CogState Brief Battery; C-SSRS = Columbia Suicide Severity Rating 
Scale; ECG = electrocardiogram; ED = early discontinuation visit; HBsAg = hepatitis B surface antigen;
HCG = human chorionic gonadotropin; HCV = hepatitis C virus; IWRS = interactive web response system; 
MHIS = Modified Hachinski Ischemia Scale; Examination; MMSE = Mini-Mental State Examination; 
MRI = magnetic resonance imaging; No. = number; PCR = polymerase chain reaction; PET = positron emission 
tomography; SHSF = Self-Harm Supplement form; SHFU = Self-Harm Follow-Up; V = visit; Wk = week.
a
The interval between V1 and V2 may be up to 63 days to allow for completion of V1 screening procedures, 
assessments, and evaluation of results from laboratory tests and ECGs.  V1 is not considered complete until all 
screening procedures have been completed and results reviewed by the investigator to determine patient 
eligibility.  V1 may be conducted over more than 1 day. Subjects in screening at the time screening was paused 
are allowed to continue screening beyond the 63 days to allow for completion of V1 screening procedures; this 
will not be a protocol deviation. Additional details are provided in Section 5.1.1. Subjects who had completed 
screening but were not yet randomized at the time randomization was paused are allowed to be randomized 
beyond 63 days; this will not be a protocol deviation.  Additional details are provided in Section 5.1.1.
b
A florbetapir F18 PET scan is the final screening criterion for establishing patient eligibility, although the MRI 
may be performed after the florbetapir F18 PET scan. Patients whose screening florbetapir F18 PET scan results 
are not available within the 63 day screening window will remain eligible within V1 until these results become 
available if all other eligibility criteria have been met.  Note:  If a patient’s screening florbetapir F18 PET scan 
result confirming eligibility for the study has not been received by the site by Day 63 of the screening period, 
then repeat the following laboratory tests:  blood hematology, chemistry, and serum pregnancy test (HCG) for 
women of childbearing potential (WOCBP).  Results of the repeated labs are to be reviewed by the investigator 
or qualified designee for assessment of the patient’s continued eligibility.  Repeat screening for MMSE, CBB, 
C-SSRS, ECG, flortaucipir F18 PET, MRI, and laboratory testing for HBsAg and HCV RNA PCR is not 
required.  V1 is not considered complete until all screening procedures have been completed and results reviewed 
by the investigator or qualified designee to determine patient eligibility.
c
A preliminary screening informed consent may be obtained to conduct initial screening to collect demographics 
data and administer the MMSE and CBB.  Patients who do not meet the MMSE screening criteria are not to have 
any other screening procedures performed with the exception of the CBB.  The CBB should be administered to 
all patients at the screening visit, regardless of the MMSE score.  They may be rescreened for the MMSE 8 
weeks after the first screen. Study partners are not required to complete the preliminary screening informed 
consent.
d
Patients who meet the MMSE screening criteria may proceed to the remaining screening procedures once they 
have given signed/dated informed consent for the full study and their study partner has given signed/dated 
informed consented to participate as a study partner.
e
A complete physical and neurological exam is to be performed at this visit.  Additional details are provided in 
Section 9.4.1.
f
Sitting blood pressure and pulse will be measured after 5 minutes in the sitting position only.  Temperature will 
be collected with sitting vital signs.
g
Height and weight will be measured with shoes removed.
h
ECGs should be taken in triplicate at approximately 1-minute intervals.  ECGs should be collected at 
approximately the same time of day, as much as possible, to minimize diurnal variation.
i
The baseline version of the C-SSRS is to be administered at V1.  Patients at imminent risk of suicide (positive 
response to question 4 or 5 on the C-SSRS) will be excluded from participating in the study.

I5T-MC-AACG(d) Clinical Protocol
Page 17
LY3002813
j
The SHSF is completed after each C-SSRS administration to enter the number of discrete events of suicidal 
behavior identified.  If, based on administration of the C-SSRS, it is determined that suicide-related behaviors 
have occurred, then the SHFU form will be used to collect additional information to allow for a more complete 
assessment of these behaviors.
k
Females of childbearing potential are to have a serum pregnancy test (HCG) at V1 (if applicable).
l
Females of childbearing potential are to have a urine pregnancy test (HCG) on the day of flortaucipir F18 PET 
imaging before the flortaucipir F18 dose is administered.
m Females of childbearing potential are to have a urine pregnancy test (HCG) on the day of florbetapir F18 PET 
imaging before the florbetapir F18 dose is administered.
n
Patients with a past history of Hepatitis B are to have a serum HBsAg test at screening V1 and are excluded if the 
HBsAg test is positive.
o
Patients with a past history of Hepatitis C are to have a HCV RNA PCR test at screening V1 and are excluded if 
the HCV RNA PCR test is positive.
p
A screening flortaucipir F18 PET scan will be performed as part of the study eligibility criteria at all sites to 
determine patient eligibility for participation in Study AACG (see Appendix 5).  With the exception of an MRI
and a florbetapir F18 PET scan, a patient should meet all other V1 eligibility criteria before having a screening 
flortaucipir F18 PET scan.  The flortaucipir F18 PET scan will be submitted to a centralized PET imaging vendor 
designated by Lilly for an assessment of patient’s eligibility.  A historical flortaucipir F18 PET scan may be 
submitted to be considered for eligibility if performed within 6 months of V1.
q
A local screening MRI will be performed at V1 as part of the study eligibility criteria.  With the exception of the 
evidence of amyloid pathology by florbetapir F18 PET scan, a patient should meet all other V1 eligibility criteria 
before having an MRI scan.  The MRI scans will be reviewed by the investigator or qualified designee for 
immediate patient management.  After the MRI scan is read locally, the scan is to be submitted to the centralized 
MRI vendor designated by Lilly for final determination of MRI eligibility.  Results of centrally read MRIs will 
be used for data analysis and report-writing purposes and patient safety and eligibility will be reported back to 
sites.
r
A screening florbetapir F18 PET scan will be performed as part of the study eligibility criteria to determine 
patient eligibility for participation in Study AACG (see Appendix 6).  With the exception of an MRI, a patient 
should meet all other V1 eligibility criteria before having a screening florbetapir F18 PET scan.  The PET scan 
will be submitted to a centralized PET imaging vendor designated by Lilly for assessment of patient’s eligibility.  
The florbetapir F18 PET screening criteria must be met (scan results consistent with the presence of amyloid 
pathology) in order for the patient to proceed to V2 and be randomized to treatment assignment.
s
Assessment is to include the audio voice recording of the rater’s questions and the patient and caregiver 
responses to assessment questions.

I5T-MC-AACG(d) Clinical Protocol
Page 18
LY3002813
Schedule of Activities, Protocol I5T-MC-AACG, Visit 2 through Visit 14 (Double-Blind Period)
Period:
Procedure
Rand
Visit No.:
V2a,b
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
V13
V14
End of Week Relative to Study Medication Start
0
4
8
12
16
20
24
28
32
36
40
44
48
Tolerance Interval for Visit (days)
0
7
7
7
7
7
7
7
7
7
7
7
7
   Inclusion/exclusion review
X
X
X
X
X
X
X
X
X
X
X
X
X
   Contact IWRS – dispensation of study medication
   (LY3002813)
X
X
X
X
X
X
X
X
X
X
X
X
X
   Physical/neurological examinatione
Xf
Xf
Xf
Xg
   Ophthalmological examinationh
j
Xh
Xh
   Dermatological examinationi
j
Xi
Xi
   Previous/concomitant medications
X
X
X
X
X
X
X
X
X
X
X
X
X
   Preexisting conditions/adverse eventse
X
X
X
X
X
X
X
X
X
X
X
X
X
   LY3002813 study medication administeredk
X
X
X
X
X
X
X
X
X
X
X
X
X
Efficacy Measures
   ADAS-Cog13
l,ff
X
X
X
X
   ADCS-ADLl,ff
X
X
X
X
   CDR-SBl,ff
X
X
X
X
   MMSEl,ff
X
X
X
Safety Assessment
   C-SSRS/SHSF/SHFUm,n
m
X
X
X
X
X
X
X
X
X
X
X
X

I5T-MC-AACG(d) Clinical Protocol
Page 19
LY3002813
Schedule of Activities, Protocol I5T-MC-AACG, Visit 2 through Visit 14 (Double-Blind Period)
Period:
Procedure
Rand
Visit No.:
V2a,b
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
V13
V14
End of Week Relative to Study Medication Start
0
4
8
12
16
20
24
28
32
36
40
44
48
Tolerance Interval for Visit (days)
0
7
7
7
7
7
7
7
7
7
7
7
7
Laboratory Specimenso
   Clinical chemistry, hematologyp
X
X
X
X
X
X
   High sensitivity C-reactive proteinp
X
X
X
X
X
X
   Urinalysisp
X
   Serum for anti-LY3002813 antibodyp
X
X
X
X
X 
X
X
   Serum LY3002813q,r
Xq
Xr
Xr
Xq
Xr
Xq
Xr
   Blood for assessment of APOE genotypep,s
X
Whole blood, plasma and serum for biomarker 
storagep,t
X
X
X
X
   Blood for pharmacogenomicsp,t,u
X
Other Safety Measures
   Weight
X
X
X
X
   Vital signs and temperaturev,w
Xw
X
X
Xw
X
X
Xw
X
X
Xw
X
X
X
   ECG in triplicatex
X
X
X
X
X
X
   MRIy
z
X
Xaa
X
X
X
Additional Efficacy Measures
  Flortaucipir F18 PET scanbb,cc
z
  Florbetapir F18 PET scanbb,dd
z
Xbb,dd

I5T-MC-AACG(d) Clinical Protocol
Page 20
LY3002813
Schedule of Activities, Protocol I5T-MC-AACG, Visit 15 through Visit 21 (Double-Blind Period) and Follow-Up
Period:
Procedure
Visit No.:
V15
V16
V17
V18
V19
V20
V21
EDc
V801-
V804d,ee
End of Week Relative to Study Medication Start
52
56
60
64
68
72
76
88-124
Tolerance Interval for Visit (days)
7
7
7
7
7
7
7
14
   Inclusion/exclusion review
X
X
X
X
X
X
   Contact IWRS – dispensation of study medications
   (LY3002813)
X
X
X
X
X
X
  
   Physical/neurological examinatione
Xf
Xg
Xf
Xf
   Ophthalmological examinationh,j
Xh
   Dermatological examinationi,j
Xi
   Previous/concomitant medications
X
X
X
X
X
X
X
X
X
   Preexisting conditions/adverse eventse
X
X
X
X
X
X
X
X
X
   LY3002813 study medication administeredk
X
X
X
X
X
X
Efficacy Measures
   ADAS-Cog13
l,ff
X
X
X
X
   ADCS-ADLl,ff
X
X
X
X
   CDR-SBl,ff
X
X
X
X
   MMSEl,ff
X
X
X
X
Safety Assessment
   C-SSRS/SHSF/SHFUm,n
X
X
X
X
X
X
X
X
X

I5T-MC-AACG(d) Clinical Protocol
Page 21
LY3002813
Schedule of Activities, Protocol I5T-MC-AACG, Visit 15 through Visit 21 (Double-Blind Period) and Follow-Up
Period:
Procedure
Visit No.:
V15
V16
V17
V18
V19
V20
V21
EDc
V801-
V804d,ee
End of Week Relative to Study Medication Start
52
56
60
64
68
72
76
88-124
Tolerance Interval for Visit (days)
7
7
7
7
7
7
7
14
Laboratory Specimenso
   Clinical chemistry, hematologyp
X
X
X
X
   High sensitivity C-reactive proteinp
X
X
X
X
   Urinalysisp
X
X
X
X
   Serum for anti-LY3002813 antibodyp
X
X
X
X
   Serum LY3002813q,r
Xq
Xr
Xq
Xr
Xr
Xr
   Blood for assessment of APOE genotypep,s
   Whole blood, plasma and serum for biomarker storagep,t
X
X
X
X
   Blood for pharmacogenomicsp,t,u
Other Safety Measures
   Weight
X
X
X
X
   Vital signs and temperaturev,w
Xw
X
X
Xw
X
X
Xw
Xw
X 
   ECG in triplicate
X
X
X
X
   MRIy
X
X
X
Additional Efficacy Measures
   Flortaucipir F18 PET Scanbb,cc
Xbb,cc
Xbb,cc
   Florbetapir F18 PET scanbb,dd
Xbb,dd
Xbb,dd
Xbb,dd

I5T-MC-AACG(d) Clinical Protocol
Page 22
LY3002813
Schedule of Activities, Protocol I5T-MC-AACG, Visit 2 through Visit 21 (Double-Blind Period) and 
Follow-Up Abbreviations and Footnotes
Abbreviations:  A= amyloid ; ADA = anti-drug antibodies; ADAS-Cog13 = 13-item Alzheimer’s Disease 
Assessment Scale-Cognitive subscore; ADCS-ADL = Alzheimer’s Disease Cooperative Study Activities of 
Daily Living Inventory; APOE = apolipoprotein subtype E; ARIA-E = amyloid related imaging abnormalities–
edema/effusions; CDR-SB = Clinical Dementia Rating-Sum of Boxes; CRF = case report form; C-SSRS = 
Columbia Suicide Severity Rating Scale; ECG = electrocardiogram; ED = early discontinuation visit; 
HCG = human chorionic gonadotropin; IWRS = interactive web response system; MMSE = Mini-Mental State 
Examination; MRI = magnetic resonance imaging; No. = number; PET = positron emission tomography; SHFU 
= Self-Harm Follow-Up form; SHSF = Self-Harm Supplement form; TE = treatment-emergent; V = visit.
a
Confirm that the patient has met all V1 eligibility criteria before proceeding with V2 procedures.
b
At V2, appointments should be made for all remaining visits and should be scheduled as close as possible to the 
target date, relative to V2.  Procedures for some visits may take more than 1 day.
c
If a patient discontinues before the double-blind period endpoint (V21 at Week 76), complete the Early 
Discontinuation CRFs.  The patient should be encouraged to return to the site beginning 12 weeks after the ED 
visit for an immunogenicity follow-up visit (V801 through V804).
d
Patients are to return to the site for collection of blood samples and safety assessments for assessment of 
immunogenicity status at V801 (Week 88).  Follow-up for patients experiencing clinically significant events 
associated with TEADA status is described in Section 9.4.7.2.
e
Any clinically significant changes from baseline on follow-up physical/neurological examinations should be 
noted on the AE page.
f
A complete physical and neurological exam is to be performed at this visit.  Additional details are provided in 
Section 9.4.1.
g
A brief physical and neurological exam is to be performed at this visit.  Additional details are provided in Section 
9.4.1.
h
Ophthalmological examinations will be performed only in patients who previously received LY3202626/oral 
placebo in this study.  The final examination for each patient will be the next scheduled ophthalmological
examination after the final administration of LY3202626/oral placebo. It will not be considered a protocol 
deviation if this examination is scheduled sooner than indicated above in order to accommodate patient and/or 
site preference.  Patients who received LY3202626/oral placebo after their V9 ophthalmological examination are 
to have an unscheduled ophthalmological examination at the next available opportunity.  These examinations
must be conducted by an ophthalmologist or optometrist (where permitted by law).  Additional details are 
provided in Section 9.4.6.3.
i
Dermatological examinations will be performed only in patients who previously received LY3202626/oral 
placebo in this study.  The final examination for each patient will be the next scheduled dermatological 
evaluation after the final administration of LY3202626/oral placebo.  It will not be considered a protocol 
deviation if this examination is scheduled sooner than indicated above in order to accommodate patient and/or 
site preference.  Patients who received LY3202626/oral placebo after their V8 dermatological examination are to 
have an unscheduled dermatological examination at the next available opportunity.  These examinations must be 
conducted by a dermatologist.  Additional details are provided in Section 9.4.6.4.
j
For subjects randomized prior to amendment (d), the ophthalmological and dermatological examination 
performed at screening will serve as the baseline ophthalmological and dermatological examination.
k
Study drug will be administered by intravenous administration at investigative study site. Patients should be 
observed for approximately 2 hours following each infusion of LY3002813 for the first 6 infusions.  After the 
first six doses, a minimal post-infusion observation time of 60 minutes will be required for all subsequent 
infusions.  However, patients who have had dosing restarted after ARIA-E are required to be monitored for 2 
hours following infusion for a minimum of 3 subsequent infusions, and a minimum of 60 minutes post-infusion 
observation thereafter.

I5T-MC-AACG(d) Clinical Protocol
Page 23
LY3002813
l
When administered, cognitive and functional assessments (ADAS-Cog13, ADCS-ADL, CDR, and MMSE) 
should be performed first, before medical procedures that could be stressful for the patient (e.g., blood draws).
m The C-SSRS administered at screening will serve as the baseline C-SSRS.
n
The ‘since last visit’ version of the C-SSRS will be administered at visits after V2 (Week 0) to the patient with 
the study partner/study informant present, after the cognitive and functional assessments.  The SHSF is 
completed after each C-SSRS administration to enter the number of discrete events of suicidal behavior 
identified.  If, based on administration of the C-SSRS, it is determined that suicide-related behaviors have 
occurred, then the SHFU form will be used to collect additional information to allow for a more complete 
assessment of these behaviors
o
Unscheduled laboratory tests may be performed at the discretion of the investigator.
p
Labs are to be collected prior to administration of the intravenous study medication (LY3002813 or IV placebo).  
Record the date and times of sample collection on the Lab Requisition Form.
q
Pre-dose (before beginning the infusion) samples for intravenous study medication (LY3002813) may be 
collected from the intravenous site prior to beginning the infusion. Post-dose (within 30 minutes of completion 
of the infusion) samples for intravenous study medication (LY3002813) should be collected from the arm that 
did not receive the infusion at V2 (Week 0), V5 (Week 12), V8 (Week 24), V15 (Week 52), and V20 (Week 72).
r
A single pre-dose LY3002813 sample should be collected before beginning the infusion at V3 (Week 4), V4 
(Week 8), V6 (Week 16), V11 (Week 36), and V18 (Week 64).  In addition, a single sample for serum 
LY3002813 should be collected at V21 (Week 76), or ED, and V801 (visits at which the patient may not receive 
a study drug infusion). If LY3002813 infusion is permanently discontinued but the patient remains in the study, 
one PK sample should be collected at the soonest scheduled visit regardless if serum LY3002813 is on the 
Schedule of Activities at that visit. Subsequent PK sample collection should follow the protocol Schedule of 
Activities for serum LY3002813 collection unless the scheduled visit exceeds 6 months since discontinuation of 
infusions. No additional serum collection for LY3002813 is required once the patient exceeds 6 months since 
discontinuation of LY3002813 infusions. Record the actual date and times of sample collection on the Lab 
Requisition Form.
s
A blood sample will be collected to determine APOE genotype.  The APOE genotype sample may be collected at 
an alternative visit if it cannot be collected at V2.
t
Blood for biomarker storage, and blood for pharmacogenomic samples are to be collected unless not allowed or 
unfeasible due to local regulations prohibiting sample transport outside of the country.
u
Pharmacogenomic samples may be collected at an alternative visit if they cannot be collected at V2.  It will not 
be a protocol deviation if a biomarker storage sample cannot be collected for technical reasons (e.g., if the site is 
unable to collect enough blood via venipuncture).
v
Sitting blood pressure and pulse will be measured after 5 minutes in the sitting position at all visits.  Temperature 
will be collected with sitting vital signs.
w In addition, orthostatic blood pressure and pulse will be measured at V2 (Week 0), V5 (Week 12), V8 (Week 24), 
V11 (Week 36), V15 (Week 52), V18 (Week 64), V21 (Week 76), or ED, and at unscheduled visits after 5 
minutes in the supine position and after 3 minutes standing.
x
Electrocardiograms should be taken in triplicate at approximately 1-minute intervals.  ECGs should be collected 
at approximately the same time of day, as much as possible, to minimize diurnal variation.  ECGs are to be 
performed prior to the administration of intravenous study medication (LY3002813 and IV placebo).
y
If MRI is done on the same day as cognitive and functional assessments, then it should be done after cognitive 
and functional tests.  MRI may be done before other visit procedures, including cognitive and functional tests, 
but in that case must be done at least 1 day before other visit procedures.
z
The screening flortaucipir F18 PET scan, MRI, and florbetapir F18 PET scan done at V1 serve as the baseline 
flortaucipir F18 PET scan, MRI, and florbetapir F18 PET scan, respectively.
aa The V5 MRI is to be performed 2 weeks prior to the V5 (Week 12) LY3002813 infusion to allow for receipt and 
review of the central vendor MRI report prior to a possible LY3002813 dose change at V5 (Week 12).

I5T-MC-AACG(d) Clinical Protocol
Page 24
LY3002813
bb Females of childbearing potential are to have a urine pregnancy test (HCG) performed on the day of florbetapir 
F18 PET and flortaucipir F18 PET imaging before the florbetapir F18 dose or flortaucipir F18 dose is 
administered to confirm that they are not pregnant.
cc All patients will have a flortaucipir F18 PET scan done at V21 (Week 76) or ED (if ED occurs more than 36
weeks after randomization) (see Appendix 5).  Before the flortaucipir F18 PET scan, the investigator should 
review the patient’s medical history and concomitant medications to verify there is no risk factor for torsades de 
pointes and review the most recent ECG. If clinically meaningful abnormalities are noted on the ECG, the 
advisability of the flortaucipir scan should be considered by the investigator in consultation with the 
Lilly-designated medical monitor. The study investigator and site clinical study team will not have access to 
the flortaucipir F18 follow-up scans, as the site clinical study team must remain blinded to any potential 
changes in tau deposition.
dd All patients will have double-blind period florbetapir F18 PET scans done at V8 (Week 24), V15 (Week 52), and 
V21 (Week 76) or ED (if ED occurs more than 8 weeks after a florbetapir F18 PET scan has been performed at a 
previous visit) (see Appendix 6).  The study investigator and site clinical study team will not have access to any 
florbetapir F18 follow-up scans, as the site clinical study team must remain blinded to any potential changes 
in amyloid deposition.
ee Patients are to return to the site for an immunogenicity and safety follow-up visit (V801) at Week 88 (or 
12 weeks after the ED visit) for collection of blood samples for anti-drug antibody (ADA) measurements and 
assessment of adverse events and concomitant medications.  The need for additional study visits after V801 will 
be determined by results of the ADA sample taken at V801. A patient will stop immunogenicity follow-up visits 
when they either complete 3 additional quarterly visits (Week 100, Week 112, and Week 124) or complete a visit 
at which their ADA returns to baseline (2-fold titer from baseline), whichever occurs first.  See Section 5.1.3 and 
Section 9.4.7.2 for details.
ff Assessment is to include the audio voice recording of the rater’s questions and the patient and caregiver 
responses to assessment questions.

I5T-MC-AACG(d) Clinical Protocol
Page 25
LY3002813
3.
Introduction
3.1.
Study Rationale
LY3002813 is an antibody directed at the pyroglutamate modification of the third amino acid of 
amyloid beta (N3pG Aβ) epitope that is present only in brain amyloid plaques.  It is being 
studied for the treatment of Alzheimer’s disease (AD).  The mechanism of action of LY3002813 
is considered to be the targeting and removal of existing amyloid plaque, which is a key 
pathological hallmark of AD.  The clinical strategy for LY3002813 targets the N3pG Aβ specific 
to amyloid plaque in the population of early symptomatic AD patients with existing brain 
amyloid load, as measured using the amyloid plaque biomarker, florbetapir F18 positron 
emission tomography (PET) imaging. This rationale is based on the amyloid hypothesis of AD,
which states that the production and deposition of Aβ is an early and necessary event in the 
pathogenesis of AD (Selkoe 2000).  Clinical support for this hypothesis comes from the 
demonstration that parenchymal Aβ levels are elevated before the appearance of symptoms of 
AD, and supported by genetic variants of AD that overproduce brain Aβ and genetic variants that 
protect against Aβ production (Jonsson et al. 2012; Fleisher et al. 2015).  Furthermore, early in 
the disease, the presence of brain amyloid appears to increase the risk of conversion from mild 
cognitive impairment (MCI) to AD dementia (Doraiswamy et al. 2012).  This suggests that 
enhanced clearance of Aβ will lead to slowing of AD progression.
Study I5T-MC-AACG (AACG) is a Phase 2, double-blind, placebo-controlled study to evaluate 
the safety and efficacy of N3pG antibody (LY3002813) in patients with early symptomatic AD 
(prodromal AD and mild dementia due to AD).  Study AACG will assess whether removal of 
existing amyloid plaque can slow the progression of disease as assessed by clinical measures and 
biomarkers of disease pathology and neurodegeneration over up to 72 weeks of treatment.
Multiple biomarkers of disease progress will also be evaluated.  The biomarker florbetapir F18 is 
a PET ligand that binds to fibrillar amyloid plaque.  This biomarker can provide a qualitative and 
quantitative measurement of brain plaque load in patients with prodromal AD or mild AD 
dementia.  The absence of significant florbetapir F18 signal on a visual read indicates that those 
patients clinically manifesting cognitive impairment have sparse to no amyloid plaques.  As 
such, implementation of florbetapir F18 will provide a screening tool for entry into the clinical 
trial and provide a confirmation of amyloid pathology.  Florbetapir F18 PET also provides 
quantitative assessment of fibrillar amyloid plaque in the brain and can assess amyloid plaque 
reductions from the brain by LY3002813.
Alzheimer’s disease progression is also associated with cerebral tauopathy, which will be 
assessed by flortaucipir F18 PET scan, a cortical marker of paired helical filaments.  Brain 
atrophy, as an indicator of neurodegeneration, will be assessed by volumetric resonance imaging 
(vMRI).
The patient population for the clinical trial is selected to be AD patients with early symptomatic 
disease defined both clinically (prodromal to mild AD dementia) and by biomarkers (low to 
medium tau burden, plus amyloid plaque presence).  The 2018 NIA-AA draft AD research 

I5T-MC-AACG(d) Clinical Protocol
Page 26
LY3002813
framework (Alzheimer’s Association 2017a) proposes that AD is defined by its underlying 
pathophysiologic processes which can be documented in vivo by biomarkers (such as tau and 
amyloid PET) or by post-mortem examination.  This framework will enable a more precise 
approach to therapeutic intervention trials where specific pathways can be targeted at specific 
points in the disease process and to the appropriate people (Alzheimer’s Association 2017b).  
Clinical-pathological correlations also strongly suggest that baseline imaging that allows staging 
on the basis of neurofibrillary tangles could substantially improve the power of clinical trials 
aimed at changing the rate of progression of the disease (Qian et al. 2017).  An early AD 
population defined clinically and pathologically is anticipated to be more homogeneous than 
populations defined without tau PET, and will be sufficiently early to respond to treatments prior 
to more advanced irreversible neuronal loss.
3.2.
Background
Alzheimer’s disease is an age-related neurodegenerative disorder characterized by progressive 
decline in cognitive function and the ability to perform activities of daily living, ultimately
resulting in dementia, typically with fatal complications.  The amyloid hypothesis of AD 
postulates that the accumulation of amyloid-β peptide (Aβ) is an early and necessary event in the 
pathogenesis of AD.  This hypothesis suggests that treatments that slow the accumulation of Aβ 
plaque in the brain or increase clearance of Aβ may be able to slow the progression of the AD 
clinical syndrome.  The other hallmark neuropathological lesion of AD, intraneuronal 
neurofibrillary tangles consisting of tau proteins, is thought to be another marker for disease 
progression (Braak and Braak 1996).  The relationship between these 2 pathologies is still 
unclear, although the presence of both is necessary for the diagnosis of definite AD.
Converging evidence from both genetic at-risk and age at-risk cohorts suggests that the 
pathophysiological process of AD begins well more than a decade before the clinical stage now 
recognized as AD dementia, and that neurodegeneration is already apparent on magnetic 
resonance imaging (MRI) by the stage of MCI.  Like many disorders, AD occurs on a continuum 
from asymptomatic (preclinical) to MCI, then to dementia in mild, moderate, and severe stages.  
Recent clinical trial results in mild-to-moderate AD dementia, as well as evidence from 
transgenic animal experiments, suggest that treating AD during the earlier stages could have the 
greatest potential benefit on the disease and its progression, particularly when considering 
therapies targeted at Aβ reduction (Doody et al. 2014; Fleisher et al. 2015; Siemers et al. 2016).
3.2.1. LY3002813 Nonclinical Studies
The safety of LY3002813, a plaque-specific monoclonal antibody, was assessed in a 6-week 
toxicity study in cynomolgus monkeys, including evaluations of safety pharmacology and 
toxicokinetics.  The administration of LY3002813 in monkeys of up to a maximum dose of 100 
mg/kg/week (bolus intravenous [IV]) for 6 weeks resulted in no drug-related findings.  Repeat-
dose hazard identification studies of up to 6 months’ duration were conducted in the aged 
PDAPP (APPV717F) transgenic mouse model of Aβ deposition to investigate potential effects 
related to clearance of Aβ from the brain.  In addition, a specialized 3-month study to investigate 
the potential for cerebral amyloid angiopathy (CAA)-associated microhemorrhage was 

I5T-MC-AACG(d) Clinical Protocol
Page 27
LY3002813
conducted in aged PDAPP transgenic mice.  These studies in the PDAPP mouse were conducted 
with mE8c (LSN3026818), a murine analog antibody of LY3002813, to avoid limitations due to 
potential immunogenicity from repeated administration of the humanized antibody to the mouse.  
No drug-related findings occurred in the hazard identification studies in PDAPP mice at mE8c 
doses of up to 100 mg/kg/week (the highest dose tested).  Treatment of PDAPP mice with mE8c 
at 12.5 mg/kg/week for 3 months did not exacerbate CAA-associated microhemorrhage at a dose 
that produced a maximum pharmacological response (reduction in deposited brain Aβ) in these 
animals.  See the Investigator’s Brochure (IB) for details regarding nonclinical LY3002813 
studies.
3.2.2. LY3002813 Phase 1 Studies
The first human dose study of LY3002813 was I5T-MC-AACC (Study AACC).  Study AACC 
was a Phase 1, patient- and investigator-blind, randomized within cohort, placebo-controlled, 
parallel-group, single-dose followed by multiple-dose, dose-escalation study in patients with 
MCI due to AD or mild-to-moderate AD to assess the safety, tolerability, pharmacodynamics 
(PD), and pharmacokinetics (PK) of single and multiple IV doses of LY3002813.  The study 
included Japanese and non-Japanese patients.  Patients with AD were enrolled into the 
single-ascending dose (SAD) phase and were each administered a single IV dose of LY3002813 
(5 dosing cohorts from 0.1 mg/kg IV to 10 mg/kg IV) or placebo followed by a 12-week 
follow-up period for each dose level.  After the follow-up period, the same patients proceeded 
into the multiple-ascending dose (MAD) phase (5 cohorts) and were administered IV doses of 
LY3002813 (0.3 mg/kg IV to 10 mg/kg IV; subjects in the 0.1 mg/kg SAD cohort received 
0.3 mg/kg in the MAD phase) or placebo approximately once per month for up to 4 doses, 
depending on the initial dose level.  This phase concluded with a 12-week follow-up period.  The 
relative exposure assessment of an unblinded single subcutaneous (SC) dose of 3 mg/kg 
LY3002813 in AD patients was also performed, followed by a 12-week follow-up assessment.  
The PK of an unblinded single IV dose of 1 mg/kg LY3002813 in young, healthy male subjects 
was assessed to determine whether the absence of the amyloid target affected the PK as 
compared with amyloid-positive AD patients.
After single-dose administration from 0.1 mg/kg to 3.0 mg/kg, the mean terminal elimination 
half-life was approximately 4 days, increasing to approximately 10 days (243 hours) at the 
10-mg/kg dose level.  The PK of a single dose of 1.0 mg/kg IV LY3002813 in young, healthy 
subjects was indistinguishable from the PK in AD patients at the same dose level.
In AACC, florbetapir F18 scans were performed at baseline and after the last MAD, separated by 
approximately 7 months, to assess the PD effects of LY3002813.  The change from baseline in 
grey matter standardized uptake value ratio (SUVr) with cerebellum as a reference region was 
compared across dose cohorts.  There was a highly significant reduction from baseline in 
cerebral amyloid by PET at the highest dose, 10 mg/kg (p<.0002).  The analysis showed 
consistent reduction in cortical amyloid among these patients who received 3 to 5 doses of 
10 mg/kg LY3002813.  The mean observed reduction in florbetapir F18 PET signal corresponds 
to a mean 50% reduction in total brain fibrillar amyloid.  Meaningful target engagement 
(amyloid reduction) was likely not achieved at doses smaller than or equal to 3 mg/kg IV every 

I5T-MC-AACG(d) Clinical Protocol
Page 28
LY3002813
4 weeks (Q4W) because of the rapid elimination of LY3002813 and the lack of sustained 
exposure.
I5T-MC-AACD (Study AACD) is an ongoing Phase 1b single- and multiple-dose study to assess 
the safety, tolerability, PK, and PD of single and multiple IV doses of LY3002813 in patients 
with mild cognitive impairment due to AD or mild to moderate Alzheimer’s dementia.  It is 
evaluating up to 150 patients in 6 different dosing cohorts receiving single, every 2 weeks, or 
every 4 weeks dosing of either 10 mg/kg, 20 mg/kg or 40 mg/kg of LY3002813.  Treatment 
durations being assessed include single dose, six month dosing every two weeks, or up to 72 
weeks of every 4 week dosing.  Safety, PK and PD data from this ongoing study are used to 
inform further development of LY3002813.  See Section 3.3 and the IB for detailed safety and 
PK information regarding LY3002813.
3.3.
Benefit/Risk Assessment
3.3.1. Benefit
There is a large unmet medical need for disease-modifying treatments for AD. Data from the 
completed Phase 1a Study AACC and from the ongoing Phase 1b Study AACD indicate a 
dramatic reduction in cerebral amyloid (as assessed by florbetapir F18 PET imaging) in 
individuals who received repeated doses of at least 10 mg/kg (IB; Fleisher et al. 2018).  Along 
with assessment of safety and tolerability of LY3002813, this study will assess whether removal 
of existing amyloid plaque will show evidence of slowed clinical decline and change in 
biomarkers of disease progression relative to placebo treatment.
Although there are currently no available disease-modifying agents for the treatment of AD, 
there are several medications approved by the Food and Drug Administration (FDA) and Health 
Canada for the treatment of symptoms of AD; these include acetylcholinesterase inhibitors (e.g., 
donepezil, galantamine, and rivastigmine) and the N-methyl D-aspartate receptor antagonist 
memantine. Because these medications are considered standard of care for the treatment of AD, 
participants in this trial will be permitted to take these medications during the course of the 
study, provided that they have been on a stable dose at the time of randomization and remain on
a stable dose throughout the study.
3.3.2. Risks
Potential risks (discussed below) for LY3002813 include, but are not limited to, formation of 
anti-drug antibodies (ADA), hypersensitivity (immediate and non-immediate, including infusion-
related reactions), and amyloid-related imaging abnormalities (ARIA).
Anti-Drug Antibodies:  High incidences of treatment-emergent anti-drug antibodies (TEADAs) 
have been observed in clinical studies with LY3002813.  Although there were no serious adverse 
events (SAEs) related to the development of ADAs in Study AACC, the incidence of TEADAs 
in LY3002813-exposed patients and subjects was >90%; in Study AACD, the incidence of 
TEADAs to date (final protocol) in LY3002813-exposed patients and subjects is approximately 
75%.  In AACD, on 10 mg/kg Q2WK dosing, one patient was observed with a highly elevated 

I5T-MC-AACG(d) Clinical Protocol
Page 29
LY3002813
ADA titer of 1:163840 on Day 144 postbaseline, with no clinical consequences.  Anti-drug 
antibodies levels may affect PD levels of drug effect.  Infusion reactions and ADAs are potential 
risks common to all large molecules.  See the IB for details regarding TEADAs.
As a high prevalence of ADAs was observed in Study AACC, a risk management plan for 
immune safety will be incorporated into the clinical trial including a protocol for management of 
infusion reactions, and standardized data collection for infusion reaction AEs.
Hypersensitivity (Immediate and Non-immediate, including infusion-related reactions):  There 
is a risk of an infusion-related reaction with LY3002813 therapy.  In Study AACC, AEs of mild 
or moderate infusion reactions were reported in 6 of 37 patients with AD who received multiple 
IV doses of LY3002813 and in 0 of the 6 healthy volunteers. In AACD one patient receiving 10 
mg/kg IV every 2 weeks had a mild infusion-related reaction and 2 mild injection site reactions.  
To mitigate the risk of hypersensitivity (immediate and non-immediate),  including infusion-
related reactions, specific study exclusion criteria related to allergy are defined in the clinical 
protocol; guidance regarding use of premedications and slowing or stopping the LY3002813 
infusion is provided in Sections 9.4.7.1.1 and 9.4.7.1.2, respectively; and a protocol for 
management of infusion reactions is included in the trial Manual of Operations.
Amyloid-Related Imaging Abnormalities:  Some anti-amyloid therapies designed to remove 
amyloid have been associated with ARIA–edema/effusions and –hemorrhage/hemosiderin 
deposition (ARIA-E and ARIA-H; also known as vasogenic edema and cerebral 
microhemorrhage, respectively) (Sperling et al. 2011).  These abnormalities are best detected on 
an MRI using fluid attenuation inversion recovery (FLAIR) sequences for ARIA-E and the T2* 
gradient-recalled echo for ARIA-H.
Potential symptoms of ARIA-E include headache, gait instability, dizziness, tremor, worsening 
cognitive function, alteration of consciousness, seizures, unsteadiness, and vomiting (Ostrowitzki 
et al. 2012; Sperling et al. 2012). However, ARIA-E can also be unaccompanied by any 
symptoms.
Microhemorrhages and superficial siderosis (ARIA-H) are often associated with ARIA-E and 
both are thought to be possibly related to removal of vascular Aβ or amyloid trafficking at the 
blood–brain barrier (Ketter et al. 2017). Moreover, ARIA-H are believed to indicate a higher 
risk for macrohemorrhage as well as for the presence of significant cerebral amyloid angiopathy.  
While ARIA does occur during the natural course of AD, there appears to be an increased risk of 
microhemorrhage with anti-amyloid antibody treatment in preclinical models and ARIA-H and 
ARIA-E in humans (e.g., bapineuzumab, gantenerumab, aducanumab [Black et al. 2010]) as 
well.
In Study AACC, two cases of asymptomatic ARIA-H, but no ARIA-E were detected by MRI.  In 
the ongoing study AACD 42 subjects received up to 13 doses of LY3002813 (~32 subjects) or 
placebo (~10 subjects) as of 03 August 2017.  Of these, one mildly symptomatic and four 
asymptomatic cases of ARIA-E, and 5 events of ARIA-H in 4 patients (including in 3 patients 
who also experienced ARIA-E) have been reported.  Two cases occurred in subjects dosed with 
10 mg/kg Q2WK, 2 occurred in subjects who received a single dose of 20 mg/kg, and one in a 

I5T-MC-AACG(d) Clinical Protocol
Page 30
LY3002813
patient who received 10 mg/kg Q4WK.  There was no clear relationship to APOE4 carrier status, 
ADA, PK or PD in these cases.  All ARIA-E resolved without clinical consequence after 
treatment discontinuation, except for one patient with asymptomatic ARIA-E that was ongoing 
on MRI as of 10 August 2017.
To mitigate the potential risk of ARIA-H and ARIA-E during treatment with LY3002813, a dose 
titration regimen will be employed utilizing an initial dose that has lower risk of ARIA-E prior to 
increasing to full study dose.  In addition, a dose reduction algorithm will be employed for 
incident ARIA during the trial (see Section 7.4.1).  No cases of ARIA will have 
dose-reintroduction if permanent dose discontinuation rules (described in Section 8.1) are met.
To further aid in mitigation of potential risks of ARIA-H and ARIA-E during treatment with 
LY3002813, the current study includes a screening MRI scan that will be used to exclude 
patients with preexisting ARIA-E, >4 microhemorrhages or more than one area of superficial 
siderosis.  In addition to scheduled MRIs, unscheduled MRIs may to be obtained at the discretion 
of the investigator upon suspicion of ARIA.  It is recommended to repeat MRIs approximately 
every 4 to 6 weeks until resolution of ARIA-E or stabilization of incident ARIA-H is 
documented.
Further guidance for management of ARIA-E and incident ARIA-H is provided in the 
Operations Manual and the protocol includes guidance on dose reduction (Section 7.4.1), 
temporary treatment discontinuation (Section 8.1.1, permanent treatment discontinuation 
(Section 8.1), and continued safety monitoring and treatment options (Section 9.4.7.4).
3.3.3. Benefit/Risk Assessment Summary
To mitigate the potential risks described in Section 3.3.2, the current study will include standard 
safety assessments; i.e., reported AEs, clinical laboratory tests, immunogenicity assessments, 
vital sign and body weight measurements, 12-lead electrocardiograms (ECGs), and physical 
examinations.
Additional safety assessments will include neurological examinations (as part of each physical 
examination), MRI examinations, and suicidality evaluations using the Columbia-Suicide 
Severity Rating Scale (C-SSRS).  The current study will use an independent external Data 
Monitoring Committee (DMC) to monitor data on an ongoing basis to ensure the continuing 
safety of patients enrolled in this study.
The current study includes placebo as a comparator, and approximately one-half of the patients 
will be randomized to placebo.  In addition, all patients participating in the study will have a 
designated study partner who will have regular contact with the patient, accompany the patient to 
study visits, and liaise with the study staff between visits as needed (see Section 6.1 for 
additional information about the role of the study partner).
In conclusion, the available non-clinical and clinical data support the intravenous administration 
of LY3002813 to the intended study population according to the proposed clinical investigation 
plan and also provide a sufficient margin of safety for the proposed design and doses.  There are 

I5T-MC-AACG(d) Clinical Protocol
Page 31
LY3002813
currently no disease-modifying treatments for AD.  The potential benefits of LY3002813 
showing disease-modifying properties in AD are considered to outweigh the potential risks.
More information about the known and expected benefits, risks, SAEs and reasonably 
anticipated AEs of LY3002813 are to be found in the IB.

I5T-MC-AACG(d) Clinical Protocol
Page 32
LY3002813
4. Objectives and Endpoints
Table AACG.4.1 shows the objectives and endpoints of the study.
Table AACG.4.1.
Objectives and Endpoints
Primary Objective
Primary Endpoint
To test the hypothesis that LY3002813 
administered for up to 72 weeks will decrease 
the cognitive and/or functional decline in 
patients with early symptomatic AD
Change in cognition and function as measured by the 
change in integrated Alzheimer’s Disease Rating Scale 
(iADRS) score from baseline to 18 months
Secondary Objectives
Secondary Endpoints
To assess the effect of LY3002813 vs. placebo
on clinical progression in patients with early 
symptomatic AD
Change from baseline to 18 months as measured by:

the change in Alzheimer’s Disease Assessment 
Scale-Cognitive subscale (ADAS-Cog13) score

the change in Clinical Dementia Rating Scale 
Sum of Boxes (CDR-SB) score

the change in Mini Mental State Examination 
(MMSE) score

the change in Alzheimer’s Disease Cooperative 
Study-instrumental Activities of Daily Living 
scale (ADCS-iADL) score 
To assess the effect of LY3002813 vs. placebo 
on brain amyloid deposition
Change in brain amyloid plaque deposition from 
baseline through 18 months as measured by florbetapir
F18 PET scan
To assess the effect of LY3002813 vs. placebo 
on brain tau deposition
Change in brain tau deposition from baseline to 
18 months as measured by flortaucipir F18 PET scan
To assess the effect of LY3002813 vs. placebo 
on brain volume measures
Change in volumetric MRI measures from baseline to 
18 months.

I5T-MC-AACG(d) Clinical Protocol
Page 33
LY3002813
Safety Objective
Safety Endpoints
To evaluate safety and tolerability of 
LY3002813

Standard safety assessments:
o
spontaneously reported adverse events 
(AEs)
o
clinical laboratory tests
o
vital sign and body weight 
measurements
o
12-lead ECGs
o
physical and neurological 
examinations

MRI (ARIA and emergent radiological 
findings)

Columbia Suicide Severity Rating Scale
(C-SSRS)
Exploratory Objectives
Exploratory Endpoints
To assess the effect of LY3002813 vs. placebo 
on clinical progression in patients with early 
symptomatic AD

the change in dependence level derived from 
ADCS-ADL scale scores
To assess peripheral PK and presence of 
anti-LY3002813 antibodies over 72 weeks

Plasma Pharmacokinetics of LY3002813

Anti-drug-antibodies (ADA) against LY3002813 
including treatment-emergent ADA and 
neutralizing antibodies.

I5T-MC-AACG(d) Clinical Protocol
Page 34
LY3002813
5.
Study Design
5.1.
Overall Design
Study AACG is a multicenter, randomized, double-blind, placebo-controlled, Phase 2 study of 
LY3002813 in subjects with early symptomatic AD.  The 133-week study includes a screening 
period of up to 9 weeks, a treatment period of up to 72 weeks with final evaluations occurring
4 weeks later at Week 76, and a 48-week immunogenicity and safety follow-up period. Subjects 
who meet entry criteria will be randomized in a 1:1 ratio to one of the following treatments:

LY3002813:  IV LY3002813 (700 mg Q4WK for the first 3 doses, then 1400 mg Q4WK)
for up to 72 weeks or

Placebo:  IV placebo Q4WK for up to 72 weeks.
The primary hypothesis being tested is that LY3002813 administered for up to 72 weeks will 
result in a significant slowing in cognitive/functional decline compared with placebo as 
measured by the change from baseline to the end of the double blind treatment period (Week 76) 
on the integrated Alzheimer’s Disease Rating Scale (iADRS), in subjects with early symptomatic 
AD (where early symptomatic AD refers to the combination of 2 stages:  prodromal AD 
[MCI-AD] and mild AD dementia; Alaka et al. 2015).
Under previous versions of this protocol, LY3002813 was administered in combination with 
LY3202626, an inhibitor of β-site amyloid precursor protein cleaving enzyme (BACE)1.  
However, as of this amendment (d), the combination therapy and the oral placebo have been 
discontinued from the study.
Abbreviations and definitions are provided in Appendix 1; clinical laboratory tests are described 
in Appendix 2; Study governance considerations are described in detail in Appendix 3; and
Hepatic monitoring tests for treatment-emergent abnormality is provided in Appendix 4.

I5T-MC-AACG(d) Clinical Protocol
Page 35
LY3002813
Figure AACG.5.1.
Illustration of study design for Clinical Protocol I5T-MC-AACG.

I5T-MC-AACG(d) Clinical Protocol
Page 36
LY3002813
5.1.1. Screening Period (Visit 1)
At or before Visit 1, the study will be explained to the patient (and his or her legal representative, 
if applicable) and study partner.  Informed consent must be obtained before any study procedures 
are conducted.  The screening period spans the time between Visit 1 to Visit 2.  Study 
assessments are shown in the Schedule of Activities (Section 2).
A preliminary screening informed consent may be obtained to conduct initial screening to collect 
demographics data and administer the Mini-Mental State Examination (MMSE) and CogState 
Brief Battery (CBB).  Patients who do not meet the MMSE screening criteria are not to have any 
other screening procedures performed with the exception of the CBB.  The CBB should be 
administered to all patients at the screening visit, regardless of the MMSE score.  They may be 
rescreened for the MMSE 8 weeks or more after the first screen (see Section 6.4). Patients who 
screen failed on the CBB in the previous version of this protocol may be reconsented and 
immediately rescreened using the MMSE (see Section 6.4).
Patients who meet the MMSE screening criteria may proceed to the remaining screening 
procedures once they have given signed/dated informed consent for the full study.
Once the MMSE criteria are met, 63 days are allowed for completion of Visit 1 screening 
assessments, procedures, and evaluation of results from laboratory tests, ECGs, physical and 
neurological examination, flortaucipir F18 PET, MRI, and florbetapir F18 PET.  Even though 
florbetapir F18 PET imaging may be the last screening procedure of the study, it is expected that 
the centrally read florbetapir F18 PET results will be available within the timeframe of 63 days.  
However, it will not be a protocol deviation should the screening florbetapir F18 PET results not 
be available until after 63 days.
Patients whose screening florbetapir F18 PET results are not available until after 63 days will 
remain eligible within Visit 1 until these results become available.  Note:  If a patient’s screening 
florbetapir F18 PET results confirming evidence of amyloid burden are received by the site after 
63 days, laboratory tests (blood hematology, chemistry, and serum human chorionic 
gonadotropin [HCG] for females of childbearing potential) are to be repeated for that patient.  
Results of the repeated labs are to be reviewed by the investigator or qualified designee for 
assessment of the patient’s continued eligibility.  Repeat screening for MMSE, CBB, C-SSRS, 
ECG, flortaucipir F18 PET imaging, and MRI, and laboratory testing for hepatitis B surface 
antigen (HBsAg) and hepatitis C virus (HCV) RNA polymerase chain reaction (PCR), is not 
required.
Patients in active screening prior to implementation of amendment (d) remain eligible within 
Visit 1 until all screening procedures are completed and results are available. This will not be a 
protocol deviation. Patients who complete Visit 1 beyond 63 days are to repeat laboratory tests 
(blood hematology, chemistry, and serum HCG for females of childbearing potential) prior to 
being randomized. The results of these laboratory tests are to be reviewed by the investigator or 
qualified designee for assessment of the patient’s continued eligibility.  Repeat screening for 
MMSE, CBB, C-SSRS, ECG, flortaucipir F18 PET imaging, MRI, and laboratory testing for 
HBsAg and HCV RNA PCR is not required.

I5T-MC-AACG(d) Clinical Protocol
Page 37
LY3002813
Visit 1 is not considered complete until all screening procedures have been completed, results 
have been reviewed by the investigator or qualified designee, and the investigator or qualified 
designee has confirmed that the patient is eligible to be randomized. Only then can the patient 
proceed to Visit 2.
Current or planned use of concomitant medications, the effects of vacations or absences on 
protocol compliance, and general compliance with the protocol will be discussed at Visit 1.  
Patients must meet eligibility criteria (Section 6.1 and Section 6.2) to continue to Visit 2.  
Patients who do not meet all inclusion criteria or who meet any exclusion criteria may be 
discontinued from the study.
5.1.1.1.
Screening Procedures
Screening entry and administrative procedures, cognitive assessments, safety assessments, and 
laboratory assessments (see Schedule of Activities in Section 2) are to be done at Visit 1 before 
the screening flortaucipir F18 PET scan, MRI, and florbetapir F18 PET scan procedures.
5.1.1.1.1. Modified Hachinski Ischemic Scale (MHIS)
The Modified Hachinski Ischemic Scale (MHIS) will be completed at Visit 1 to exclude patients 
likely to have dementia of vascular etiology.  The MHIS (Hachinski et al. 1975) is an 8-item 
scale that examines clinical features that may be consistent with vascular dementia and is 
commonly used as a screening tool to exclude patients with multi-infarct dementia from entrance 
into clinical trials assessing neuropsychopharmacologic therapy in patients with AD.  The scale 
is completed by the physician based on clinical information obtained from diagnostic 
information and physical examination.  The scale takes about 10 to 15 minutes to complete, 
depending on the availability of the data needed.  Scores for the 8 items are added together for a 
total score.  Patients who score ≥4 are more likely to have a dementia of vascular etiology and 
are excluded from participating in the trial.
5.1.1.1.2. Mini-Mental State Examination (MMSE)
The MMSE will be administered to patients at Visit 1 to determine if the patient meets entry 
criteria for cognitive impairment. The MMSE is a brief instrument used to assess cognitive 
function in patients (Folstein et al. 1975).  The MMSE should be administered by the same rater 
from visit to visit to reduce potential variability.  The instrument is divided into 2 sections.  The 
first section measures orientation, memory, and attention.  The maximum score for the first 
section is 21.  The second section tests the ability of the patient to name objects, follow verbal 
and written commands, write a sentence, and copy figures.  The maximum score for the second 
section is 9.  The range for the total MMSE score is 0 to 30, with lower scores indicating great 
level of impairment.
5.1.1.1.3. CogState Brief Battery
The CBB is a brief (15-18 minute), computer-based cognitive test battery designed to measure 
psychomotor function, attention, working memory, and memory (Maruff et al. 2009, 2013; 
Fredrickson et al. 2010; Darby et al. 2012).  The CBB has been shown to be sensitive to 
AD-related cognitive decline in healthy older adults and in adults with amnestic MCI (Darby et 

I5T-MC-AACG(d) Clinical Protocol
Page 38
LY3002813
al. 2002, 2012; Lim et al. 2013a, b) as well as to improvement in cognition arising from 
treatment with cognitive-enhancing drugs (Davison et al. 2011; Jaeger et al. 2011; Nathan et al. 
2013).  The CBB will be administered at Visit 1 to better understand the utility of this test in 
assessment of cognitive impairment, but patient eligibility will not depend on the CBB results to 
determine if the patient meets the cognitive criteria for the study. The CBB will be administered 
to patients at Visit 1 after administration of the MMSE regardless of whether the patient meets 
MMSE entry criteria.  Prior to performing the screening CBB, patients must perform a practice 
CBB to familiarize themselves with the instrument.
5.1.1.1.4. Columbia Suicide Severity Rating Scale – Adult Version
The C-SSRS will be administered to patients at Visit 1 to assess psychological health.  The 
C-SSRS is a scale that captures the occurrence, severity, and frequency of suicide-related 
thoughts and behaviors during the corresponding assessment period.  The C-SSRS, included here 
as a screening assessment, is described in detail in Section 9.4.6.1.  The C-SSRS “Baseline” 
version will be used at screening, and the findings will constitute the baseline assessment.  
Patients at imminent risk of suicide (positive response to question 4 or 5 on the C-SSRS) will be 
excluded from participating in the study.
The C-SSRS will be administered to the subject after the cognitive assessments.  Responses from 
subject will be considered when administering the scale.  The Self-Harm Supplement form 
(SHSF) will be completed after each C-SSRS administration to enter the number of discrete 
events of suicidal behavior identified.  If, based on administration of the C-SSRS, it is 
determined that suicide-related behaviors have occurred, then the Lilly Self-Harm Follow-Up 
form will be used to collect additional information to allow for a more complete assessment of 
these behaviors.
5.1.1.1.5. Screening Positron Emission Tomography and Magnetic Resonance 
Imaging
All other screening criteria should be met in order for the patient to proceed with flortaucipir F18 
PET scan, followed by MRI, and a florbetapir F18 PET scan procedure.
5.1.1.1.5.1.
Screening Flortaucipir F18 PET Scan
A screening flortaucipir F18 PET scan will be performed as part of the study eligibility criteria 
(see Appendix 5).  The flortaucipir F18 PET scan will be submitted to a centralized PET imaging 
vendor designated by Lilly for assessment of patient’s eligibility.
A historical flortaucipir F18 PET scan may be submitted to be considered for eligibility if the 
PET scan was performed within 6 months of Visit 1.  If a historical flortaucipir PET scan is 
deemed acceptable for meeting entry criteria, then the MMSE, which is still to be administered at 
Visit 1, will serve as the baseline MMSE for statistical analyses, but will not be used for meeting 
entry criteria.
The flortaucipir F18 PET screening criteria should be met (scan results consistent with sponsor-
derived eligibility limits for flortaucipir F18 PET) before the patient can undergo the MRI and 
florbetapir F18 PET scan.

I5T-MC-AACG(d) Clinical Protocol
Page 39
LY3002813
Specific instructions for the flortaucipir F18 PET scan itself will be provided in the PET Imaging 
Manual.
5.1.1.1.5.2.
Screening MRI
A local screening MRI will be performed at Visit 1 as part of the study eligibility criteria.  With 
the exception of the evidence of amyloid pathology by florbetapir F18 PET scan, a patient should 
meet all other Visit 1 eligibility criteria before having an MRI.  The MRI scans will be reviewed 
by the investigator or qualified designee for immediate patient management.  After the MRI scan 
is read locally, the scan is to be submitted to the centralized MRI vendor designated by Lilly for 
final determination of MRI eligibility.  Results of centrally read MRIs will be used for data 
analysis and report-writing purposes and patient safety and eligibility will be reported back to 
sites.
5.1.1.1.5.3.
Screening Florbetapir F18 PET Scan
A screening florbetapir F18 PET scan will be performed as part of the study eligibility criteria 
(see Appendix 6).  With the exception of the MRI, a patient should meet all other Visit 1 
eligibility criteria before having a screening florbetapir F18 PET scan.  The florbetapir F18 PET 
scan will be submitted to a centralized PET imaging vendor designated by Lilly for assessment 
of patient’s eligibility.
The florbetapir F18 PET screening criteria must be met (scan results consistent with 
sponsor-derived eligibility limits for amyloid plaque pathology) in order for the patient to 
proceed to Visit 2 and be randomized to treatment assignment.
Specific instructions for the florbetapir F18 PET scan itself will be provided in the PET Imaging
Manual.
5.1.2. Double-Blind Period (Visit 2 through Visit 21)
The treatment period is a double-blind treatment phase beginning at Visit 2.  At Visit 2, 
appointments should be made for all remaining visits and should be scheduled as close as 
possible to the target date, relative to Visit 2.  Patients who meet entry criteria will be enrolled 
and randomized to receive up to 72 weeks of treatment with LY3002813 or placebo.
Every 4 weeks during this treatment period, all patients will be administered IV study medication 
(placebo or LY3002813) onsite as an IV infusion of approximately 140 mL over a minimum of 
30 minutes, and assessments will be made.
Final endpoint measures and safety assessments for the double-blind period will be performed at 
Visit 21 (Week 76) 4 weeks following the patient’s last dose of study medication.  See the 
Schedule of Activities (Section 2) for the timing of events and the measures to be assessed.  
Procedures for some visits may take more than 1 day.
The study investigator and site clinical study team will not have access to any florbetapir F18 
and flortaucipir F18 follow-up PET scans, as the investigator and site clinical study team must 
remain blinded to any potential changes in amyloid deposition.

I5T-MC-AACG(d) Clinical Protocol
Page 40
LY3002813
5.1.3. Immunogenicity and Safety Follow-up Visits (Visits 801
through 804)
Patients are to return to the site for an immunogenicity and safety follow-up visits (Visit 801
through Visit 804) beginning at Week 88 (or 12 weeks after their last dose of LY3002813) for 
collection of blood samples for anti-drug antibody (ADA; anti-LY3002813 antibody) and PK 
measurement, assessment of adverse events, C-SSRS, concomitant medications, and vital signs.
A patient will continue to return to the site for quarterly immunogenicity and safety follow-up 
visits (V802 [Week 100], V803 [Week 112], and V804 [Week 124]) until the patient completes 
V804 or the site is notified that the patient meets criteria for discharge from immunogenicity and 
safety follow-up, whichever occurs first (see Section 9.4.7.2 for details).  See the Schedule of 
Activities (Section 2) for the timing of events and the measures to be assessed.
5.2.
Number of Participants
Approximately 266 participants will be randomized.
5.3.
End of Study Definition
End of the study is the date of the last visit or last scheduled procedure shown in the Schedule of 
Activities (Section 2) for the last patient.
5.4.
Scientific Rationale for Study Design
Continuing Standard of Care.  Patients may take AD symptomatic medications such as 
concomitant acetylcholinesterase inhibitors (AChEIs) and/or memantine and/or Axona if such 
medications are standard of care (SOC) in the patient’s country and have been given for at least 
4 months and stable dosing has been maintained for at least 2 months before Visit 2.  During the 
double-blind treatment period (V2 to V21), changes in doses of available symptomatic 
medications for MCI or AD will require reporting to the sponsor and these changes should occur 
only when necessary for the adequate overall care of the patient.  The effect of LY3002813 
treatment plus SOC will be compared with placebo plus SOC.
Dosing.  As described more fully in Section 7.1, LY3002813 (700 mg or 1400 mg) will be 
administered every 4 weeks as an IV infusion of approximately 140 mL over a minimum of 
30 minutes.
Design.  Study AACG is a multicenter, randomized, double-blind, placebo-controlled study of 
LY3002813 in patients with early symptomatic AD (where early symptomatic AD refers to the 
combination of 2 stages:  prodromal AD [MCI-AD] and mild AD dementia) (Alaka et al. 2015).  
The study is intended to characterize the benefits and risks of treatment with LY3002813 versus 
placebo in patients early symptomatic AD.
Study AACG includes a placebo treatment arm and allows all patients to continue their AD 
standard of care concomitant medications.  Inclusion of a placebo treatment arm is acceptable in 
Study AACG because there are no available disease-modifying treatments for AD; this approach 
is in agreement with the use of placebo described in the Declaration of Helsinki (World Medical 

I5T-MC-AACG(d) Clinical Protocol
Page 41
LY3002813
Association 2013).  The use of a placebo comparator in Study AACG is needed to determine 
efficacy and safety of LY3002813 therapy.
The study includes a screening visit, which can last up to 63 days, at which patients are required 
to have PET flortaucipir F18 PET and florbetapir F18 PET imaging results consistent with tau 
and amyloid pathology in order to be randomized to the double-blind period.  The duration of the 
double-blind period of the study is 76 weeks and includes up to 72 weeks of treatment, with 
endpoint measures and safety assessments at the end of the double-blind treatment period (Week 
76), to assess the safety, tolerability and efficacy of LY3002813 versus placebo.
In addition to AE reporting, safety measures such as laboratory assessments, immunogenicity 
testing, vital signs and weight monitoring, ECG monitoring, physical examinations, neurological 
examinations, MRI assessments, and assessments of suicidal ideation and behavior are included 
to facilitate a comprehensive safety evaluation.  For patients enrolled under previous versions of 
this protocol, which included a combination arm of LY3002813 (N3pG) and LY3202626 (BACE 
inhibitor-IV), final dermatological examinations by a dermatologist and final comprehensive 
ophthalmological examinations by an ophthalmologist or optometrist (where permitted by law) 
will be performed at the next visit occurring after the patient stopped receiving LY3202626/oral 
placebo.
5.5.
Justification for Dose
LY3002813 doses of 700 mg and 1400 mg administered intravenously once every 4 weeks were 
selected based on current preclinical pharmacology and toxicology data and clinical PK, PD, and 
safety data.  Prior and ongoing exposures include 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 
10 mg/kg, 20 mg/kg, and 40 mg/kg in single and/or multi-dose dosing schedules.  Data from 
Study AACC and AACD suggested that PK of LY3002813 is linear when the dose is not less 
than 10 mg/kg.  Mean half-life was about 9-11 days when dose is ≥10 mg/kg, so minimal 
accumulation in plasma PK was predicted for 700 mg and 1400 mg Q4 week IV dosing.  High 
levels of florbetapir F18 PET signal reductions were seen with a single dose of 20 mg/kg, and 
were comparable to florbetapir F18 PET reductions seen with a 10 mg/kg Q2 week dosing 
schedule at 3 months (see Section 3.2 and the IB for details).  Based on this as well as decreased 
patient burden with an every 4 week dosing schedule compared with an every 2 week dosing 
schedule and comparable safety (see Section 3.3), 1400 mg Q4 week dosing was selected as the 
highest dose regimen for robust amyloid plaque lowering.  As noted in Section 3.3.2, the lowest 
rate of ARIA-E has been observed with 10 mg/kg monthly dosing.  For this reason, a titration 
schedule (700 mg Q4 week for the first 3 doses, then 1400 mg Q4 week) is proposed to reduce 
ARIA incidence while enabling patients to achieve high PD effects.  In addition, dose reduction 
rules have been established for incident ARIA-E (see Section 7.4.1).

I5T-MC-AACG(d) Clinical Protocol
Page 42
LY3002813
6. Study Population
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted.
6.1.
Inclusion Criteria
Patients are eligible for enrollment in the study only if they meet all of the following criteria:
Type of Patient and Disease Characteristics
[1]
Gradual and progressive change in memory function reported by patients or 
informants for ≥ 6 months.
[50] [Note:  Criterion #50 has been replaced by criterion #59.]
[59] An MMSE score of 20 to 28 (inclusive) at Visit 1 or an acceptable historical 
flortaucipir PET scan within 6 months prior to Visit 1 that meets the central read 
criteria.
[51] Meet flortaucipir F18 scan (central read) criteria.
[52] Meet florbetapir F18 scan (central read) criteria.
Patient/Subject Characteristics
[2]
Men or women, 60 to 85 years of age, inclusive, at the time of informed consent.
[3]
Contraception
a.  Male subjects
i. Male subjects, regardless of their fertility status, with non-pregnant female 
partners of childbearing potential must agree to either remain abstinent (if 
this is their preferred and usual lifestyle) or use condoms as well as one 
additional highly effective (less than 1% failure rate) method of 
contraception (such as combination oral contraceptives, implanted 
contraceptives, or intrauterine devices) or effective method of contraception 
(such as diaphragms with spermicide or cervical sponges) for 90 days after 
study drug dosing.
ii. Men and their partners may choose to use a double–barrier method of 
contraception.  Barrier protection methods without concomitant use of a spermicide 
are not an effective or acceptable method of contraception.  Thus, each barrier 
method must include use of a spermicide.  It should be noted, however, that the use 
of male and female condoms as a double barrier method is not considered 
acceptable due to the high failure rate when these barrier methods are combined.
iii. Male subjects with pregnant partners should use condoms during intercourse for 
the duration of the study and until the end of estimated relevant potential exposure 
in women of childbearing potential, predicted to be 90 days following last dose of 
study drug.

I5T-MC-AACG(d) Clinical Protocol
Page 43
LY3002813
iv. Male subjects should refrain from sperm donation for the duration of the study 
and until 90 days following last dose of study drug.
v. Male subjects who are in exclusively same sex relationships (as their preferred 
and usual lifestyle) are not required to use contraception.
b. Women
i. Women of childbearing potential (WOCBP) must be using or willing to use two
forms of effective contraception (e.g., combined oral contraceptive, intrauterine 
device, spermicide), for the duration of their participation in the trial and for an 
additional 3 months after their participation ends or
ii. Women not of childbearing potential are defined as those who are:
a) Infertile due to surgical sterilization (hysterectomy, bilateral 
oophorectomy, or tubal ligation),
b) Post-menopausal – defined as either
i) A woman 55 or older not on hormone therapy, who has had at least 
6 months of spontaneous amenorrhea; or
ii) A woman at least 55 years of age with a diagnosis of menopause 
prior to starting hormone replacement therapy.
iii. All female patients of child-bearing potential must test negative for pregnancy at 
Visit 1 based on serum pregnancy test.
[4]
Have a study partner who will provide written informed consent to participate, is 
in frequent  contact with the patient (defined as at least 10 hours per week), and 
will accompany the patient to study visits or be available by telephone at 
designated times.  
A second study partner may serve as backup.  The study partner(s) is/are required 
to accompany the patient for signing consent.  One study partner is requested to be 
present on all days the C-SSRS/Self-Harm Supplement Form is administered and 
must be present on all days the cognitive and functional scales are administered
(i.e., Visits 1, 2, 5, 8, 11, 15, 18, and 21/early discontinuation [ED]).  If a patient 
has a second study partner, it is preferred that one study partner be primarily 
responsible for the CDR and ADCS-ADL assessments.  If a study partner(s) is not 
able to accompany the patient in person for visits other than those listed above, 
they must be available by telephone for the following assessments:

AEs and concomitant medications

relevant portions of the C-SSRS/Self-Harm Supplement Forms
If a study partner must withdraw from study participation, a replacement may be allowed 
at the investigator’s discretion.  The replacement will need to sign a separate informed 
consent on the first visit that he/she accompanies the patient to participate.

I5T-MC-AACG(d) Clinical Protocol
Page 44
LY3002813
Study partners must be able to communicate with site personnel and be willing to comply 
with protocol requirements, and in the investigator’s opinion must have adequate literacy 
to complete the protocol-specified questionnaires.
[5]
Have adequate premorbid literacy, vision, and hearing for neuropsychological 
testing in the opinion of the investigator.
[6]
Have given written informed consent approved by Lilly and the ethical review 
board (ERB) governing the site.
[7]
Are reliable and willing to make themselves available for the duration of the study 
and are willing to follow study procedures.
6.2.
Exclusion Criteria
Patients will be excluded from study enrollment if they meet any of the following criteria:
Medical Conditions
[8]
Have a Modified Hachinski Ischemia Scale (MHIS; Hachinski et al. 1975) score of 
≥4.
[9]
Lack, in the investigator’s opinion, of adequate premorbid literacy, adequate 
vision, or adequate hearing to complete the required psychometric tests.
[10] Significant neurological disease affecting the central nervous system (CNS), other 
than AD, that may affect cognition or ability to complete the study, including but 
not limited to, other dementias, serious infection of the brain, Parkinson’s disease, 
multiple concussions, or epilepsy or recurrent seizures (except febrile childhood 
seizures).
[11] Current serious or unstable illnesses including cardiovascular, hepatic, renal, 
gastroenterologic, respiratory, endocrinologic, neurologic (other than AD), 
psychiatric, immunologic, or hematologic disease and other conditions that, in the 
investigator’s opinion, could interfere with the analyses in this study; or has a life 
expectancy of <24 months.
[12] History of cancer within the last 5 years, with the exception of non-metastatic 
basal and/or squamous cell carcinoma of the skin, in situ cervical cancer, non-
progressive prostate cancer, or other cancers with low risk of recurrence or spread.
[13] Patients with any current primary psychiatric diagnosis other than AD if, in the 
judgment of the investigator, the psychiatric disorder or symptom is likely to 
confound interpretation of drug effect, affect cognitive assessment, or affect the 
patient’s ability to complete the study. [Patients with history of schizophrenia or 
other chronic psychosis are excluded.]
[14] Have a history of long QT syndrome.
[15] Are clinically judged by the investigator to be at serious risk for suicide as 
assessed by medical history, examination, or the C-SSRS.
[16] [Note:  Criterion #16 has been replaced by criterion #57.]

I5T-MC-AACG(d) Clinical Protocol
Page 45
LY3002813
[57] [Note:  Criterion #57 has been deleted.]
[17] History of alcohol or drug use disorder (except tobacco use disorder) within 2 years before 
the screening visit.
[18] [Note:  Criterion #18 has been deleted.]
[19] Have a history of clinically significant multiple or severe drug allergies, or severe post-
treatment hypersensitivity reactions (including but not limited to erythema multiforme 
major, linear immunoglobulin A dermatosis, toxic epidermal necrolysis, and/or exfoliative 
dermatitis).
[20] Known positive serologic findings for human immunodeficiency virus (HIV) antibodies.  
Local laws and regulations may apply to whether testing is required.
Magnetic Resonance Imaging, Vital Signs, Electrocardiograms, Laboratory Tests, and 
Physical Examination
[21] Have any clinically important abnormality at screening, as determined by investigator, in 
physical or neurological examination, vital signs, ECG, or clinical laboratory test results 
that could be detrimental to the patient, could compromise the study, or show evidence of 
other etiologies for dementia.
[22] Screening MRI which shows evidence of significant abnormality that would suggest 
another potential etiology for progressive dementia or a clinically significant finding that 
may impact the patient’s ability to safely participate in the study.
[23] Have any contraindications for MRI, including claustrophobia or the presence of 
contraindicated metal (ferromagnetic) implants/cardiac pacemaker.
[24] [Note:  Criterion #24 has been replaced by criterion #58.]
[58] Have a centrally read MRI demonstrating presence of ARIA-E, >4 cerebral 
microhemorrhages, more than 1 area of superficial siderosis, any macrohemorrhage or 
severe white matter disease.
[25] An average (ECG in triplicate) corrected QT (QTcF) interval measurement >450 msec 
(men) or >470 msec (women) at screening (as determined at the investigational site).  The 
site may request a central read prior to making determination of this criterion.
[26] [Note: Criterion #26 has been replaced by criterion #53.]
[53] Patients with a past history of Hepatitis B should have HBsAg testing at screening and are 
excluded if HBsAg is positive.
[27] [Note: Criterion #27 has been replaced by criterion #54.]
[54] Patients with past history of Hepatitis C should have HCV RNA PCR testing at screening 
and are excluded if HCV RNA PCR is positive.
[28] Calculated creatinine clearance <30 mL/min (Cockcroft-Gault formula; Cockcroft 
and Gault 1976) at screening.

I5T-MC-AACG(d) Clinical Protocol
Page 46
LY3002813
[29] Alanine transaminase (ALT) ≥2X the upper limit of normal (ULN) of the performing 
laboratory, aspartate aminotransferase (AST) ≥2X ULN, total bilirubin level (TBL) ≥1.5X 
ULN, or alkaline phosphatase (ALP) ≥1.5X ULN at screening.
NOTE:  Patients with TBL ≥1.5X ULN are not excluded if they meet all of the 
following criteria for Gilbert syndrome:
1. Bilirubin is predominantly indirect (unconjugated) at screening (direct bilirubin 
within normal limits).
2. Absence of liver disease.
3. ALT, AST, and ALP ≤1X ULN at screening.
4. Hemoglobin is not significantly decreased at screening.
Prior/Concomitant Therapy
[30] Have received treatment with a stable dose of an acetylcholinesterase inhibitor 
(AChEI) and/or memantine for less than 2 months before randomization. [If a 
patient has recently stopped an AChEI and/or memantine, he or she must have 
discontinued treatment at least 2 months before randomization.]
[31] Changes in concomitant medications that could potentially affect cognition and 
their dosing should be stable for at least 1 month before screening, and between 
screening and randomization (does not apply to medications discontinued due to 
exclusions or with limited duration of use, such as antibiotics).
[32] [Note:  Criterion #32 has been deleted.]
[33] Current use of drugs known to significantly prolong the QT interval (see the 
Manual of Operations for a list of excluded drugs).
[34] Have had prior treatment with a passive anti-amyloid immunotherapy <5 half-lives 
prior to randomization.
[35] Have received active immunization against Aβ in any other study.
[36] Have known allergies to LY3002813, related compounds, or any components of 
the formulation; or history of significant atopy.
[37] [Note: Criterion #37 has been deleted.]
[38] Have allergies to either monoclonal antibodies, diphenhydramine, epinephrine, or 
methylprednisolone.
Procedural
[39] Sensitivity to florbetapir F18 or flortaucipir F18.
[40] Intend to use drugs known to significantly prolong the QT interval within 14 days 
or 5 half-lives, whichever is longer, of a scheduled screening/baseline flortaucipir 
F18 PET scan, or have a medical history of a risk factor of torsades de pointes.
[41] Poor venous access.

I5T-MC-AACG(d) Clinical Protocol
Page 47
LY3002813
[42] Contraindication to MRI.
[43] Contraindication to PET.
[44] Present or planned exposure to ionizing radiation that, in combination with the 
planned administration of study PET ligands, would result in a cumulative 
exposure that exceeds local recommended exposure limits.
Prior/Concurrent Clinical Trial Experience
[45] Are currently enrolled in any other interventional clinical trial involving an 
investigational product or any other type of medical research judged not to be 
scientifically or medically compatible with this study.
[46] Have participated, within the last 30 days (4 months for studies conducted in 
Japan; 3 months for studies conducted in the UK), in a clinical trial involving an 
investigational product.  If the previous investigational product is scientifically or 
medically incompatible with this study and has a long half-life, 3 months or 5 half-
lives (whichever is longer) should have passed prior to screening (Participation in 
observational studies may be permitted upon review of the observational study 
protocol and approval by the sponsor).
[47] [Note: Criterion #47 has been replaced by criterion #55.]
[55] Have previously completed or withdrawn from this study or received LY3002813 
in any prior investigational study.  (This exclusion criterion does not apply to 
patients who are allowed to rescreen before randomization in this study).
[56] [Note: Criterion #56 has been deleted.]
Other Exclusions
[48] Are investigator site personnel directly affiliated with this study and/or their 
immediate families.  Immediate family is defined as a spouse, parent, child, or 
sibling, whether biological or legally adopted.
[49] Are Lilly employees or are employees of third-party organizations (TPOs) 
involved in study who require exclusion of their employees, or have study partners 
who are Lilly employees or are employees of TPOs involved in a study which 
require exclusion of their employees.
6.2.1. Rationale for Exclusion of Certain Study Candidates
The use of LY3002813 in older patients is anticipated; thus this study will specifically examine 
the efficacy and safety in an elderly population.  Criterion [2] defines the population age range 
for the purposes of this study.  Therefore, patients not meeting the age criterion are excluded.
6.3.
Lifestyle Restrictions
1. Patients should refrain from donating blood or blood products from the time of their 
screening visit until 6 months following the last dose of study drug.

I5T-MC-AACG(d) Clinical Protocol
Page 48
LY3002813
2. Patients should avoid excessive use of alcohol from the screening visit until the study 
ends.  Excessive alcohol consumption is defined for men as consuming an average of 
more than 3 drinks per day, or more than 21 drinks per week.  For women, excessive use 
of alcohol is defined as consuming an average of more than 2 drinks per day, or more 
than 14 drinks per week.
6.4.
Screen Failures
Individuals who do not meet the criteria for participation in this study (screen failure) may not be 
rescreened if the screen failure is due to non-eligible imaging results.  If the screen failure is due 
to not meeting cognitive criteria on the MMSE, then one rescreen will be allowed after 8 weeks.  
If a patient failed the CBB screening in the previous version of this protocol, then the patient 
may be reconsented and immediately rescreened using the MMSE. Other reasons for screen fail 
will require sponsor approval for rescreen.

I5T-MC-AACG(d) Clinical Protocol
Page 49
LY3002813
7.
Treatments
7.1.
Treatments Administered
This study involves a comparison of LY3002813 administered as an IV infusion of 
approximately 140 mL over a minimum of 30 minutes compared with placebo.  In the double-
blind period, the treatment groups will be given an IV infusion of LY3002813 or placebo for up 
to 72 weeks.
Patients whose amyloid plaque reduction as measured by florbetapir F18 PET scans at Visit 8 
(Week 24) and/or Visit 15 (Week 52) meet criteria will have a double-blinded dose reduction of 
LY3002813 to 700 mg or IV placebo, based on the specific level of florbetapir F18 PET signal at 
that time, for the remaining duration of the double-blind treatment period.  These dose reduction 
rules may be modified by the sponsor based on ongoing collection of PD and safety data.  If 
ARIA-E occurs prior to Visit 5 (Week 12), the LY3002813 dose will not be escalated.
Table AACG.7.1 shows the 2 treatment regimens during the double-blind period.
The study also includes the use of the diagnostics flortaucipir F18 PET (for the determination of 
paired helical filament deposits of tau [tau PHF deposits]) and florbetapir F18 PET (for the 
determination of brain amyloid plaque deposits).  Information regarding the use of these 
diagnostics in the study is provided in Appendix 5 and Appendix 6, respectively.
Table AACG.7.1.
Treatment Regimens, Double-Blind Period
Regimen
Dose
Visit 2 (Week 0) through Visit 21 (Week 76)
LY3002813
LY3002813 (700 mg intravenous infusion every 4 weeks x 3 doses, then 1400 mg 
intravenous infusion every 4 weeks for up to 72 weeks)
Placebo
Intravenously dosed placebo infusion every 4 weeks for up to 72 weeks 
LY3002813 will be prepared by an unblinded pharmacist or other qualified unblinded personnel.  
LY3002813 will be administered by a blinded nurse or other qualified blinded personnel.  The 
investigator or his/her designee is responsible for the following:

explaining the correct use of the investigational agent(s) to the subject and/or 
legal representative

verifying that instructions are followed properly

maintaining accurate records of investigational product dispensing and collection

at the end of the study returning all unused medication to Lilly, or its designee, 
unless the sponsor and sites have agreed all unused medication is to be destroyed 
by the site, as allowed by local law
7.1.1. Packaging and Labelling
Clinical study materials will be labeled according to the country’s regulatory requirements.

I5T-MC-AACG(d) Clinical Protocol
Page 50
LY3002813
7.1.1.1.
LY3002813 Packaging and Labelling
The drug product LY3002813 is supplied
 
.  The drug 
product should be stored according to instructions on the label. 
 
 
Placebo is 0.9% (normal) saline.
7.2.
Method of Treatment Assignment
Patients who meet all criteria for enrollment will be assigned a study (patient) number at Visit 1 
and randomized to double-blind treatment at Visit 2.  Patients will be randomized to LY3002813 
or Placebo in a 1:1 ratio.  For between-group comparability for site factor, patient randomization 
will be stratified by investigative site.  Assignment to treatment groups will be determined by a 
computer-generated random sequence using an interactive web response system (IWRS).
The IWRS will be used to assign a dosing regimen to each patient.  Site personnel will confirm 
that they have located the correct packages by entering a confirmation number found on the label 
into the IWRS.
7.2.1. Selection and Timing of Doses
Assessment of LY3002813 safety and tolerability is a central objective; therefore, monitoring 
100 patients on LY3002813 over 72 weeks provides data to assess safety for further clinical 
development.
The actual time of LY3002813 dose administration on the day of study visits will be recorded in 
the subject’s case report form (CRF).
Note that at visits at which cognitive assessments are to be done, all cognitive scales are to be 
administered before IV study medication (LY3002813 or IV placebo) is administered.
7.2.1.1.
LY3002813:  Selection and Timing of Doses
The actual time of LY3002813 dose administrations on the day of study visits will be recorded in 
the subject’s CRF.  Intravenous study medication (i.e., IV placebo or LY3002813) is to be 
administered once every 4 weeks.  Based on the permitted visit window (see Section 2), IV study 
medication could theoretically be administered at a 2-week interval.  However, IV study 
medication must not be given at a dosing interval of less than 21 days at any time during the 
study.  Intravenous study medication given at a dosing interval of less than 21 days at any time 
during the study will be considered a protocol deviation.  The dose of LY3002813 was chosen 
based on PK/PD and safety from Studies AACC and AACD (see Section 5.5).
CCI
CCI

I5T-MC-AACG(d) Clinical Protocol
Page 51
LY3002813
Infusions should occur over the course of a minimum of 30 minutes.  If a patient demonstrates an 
infusion reaction to LY3002813, rescue medications may be administered at the discretion of the 
investigator (see Section 7.7). If indicated, the patient may be premedicated for subsequent 
infusions. See Section 9.4.7.1.1 or contact sponsor for further guidance.  Patients should be 
observed for approximately 2 hours following each infusion of LY3002813 for the first 6
infusions.  After the first 6 doses, a minimal post-infusion observation time of 60 minutes will be 
required for all subsequent infusions.  However, patients who have had dosing restarted after 
ARIA-E are required to be monitored for 2 hours following infusion for a minimum of 3 
subsequent infusions, and a minimum of 60 minutes postinfusion observation thereafter.
Sites must have resuscitation equipment available.
7.3.
Blinding
This is a double-blind study, with design to maintain blinding to treatment.  To preserve the 
blinding of the study, a minimal number of Lilly personnel will see the randomization table and 
treatment assignments before the study is complete.  The independent external DMC will 
potentially be unblinded for safety evaluations and dose reduction decisions related to safety.
Emergency unblinding for AEs may be performed through the IWRS.  This option may be used 
ONLY if the subject’s well-being requires knowledge of the subject’s treatment assignment.  All 
unblinding events are recorded and reported by the IWRS.
If an investigator, site personnel performing assessments, or subject is unblinded, the subject 
must be discontinued from the study.  In cases where there are ethical reasons to have the subject 
remain in the study, the investigator must obtain specific approval from a Lilly clinical research 
physician (CRP) for the subject to continue in the study.
In case of an emergency, the investigator has the sole responsibility for determining if unblinding 
of a patient’s treatment assignment is warranted for medical management of the event.  The 
patient’s safety must always be the first consideration in making such a determination.  If a 
patient’s treatment assignment is unblinded, Lilly must be notified immediately.  If the 
investigator decides that unblinding is warranted, it is the responsibility of the investigator to 
promptly document the decision and rationale and notify Lilly as soon as possible.
7.4.
Dosage Modification
7.4.1. LY3002813 Dosage Modification for ARIA-E
LY3002813 dosage modifications will be done for the occurrence of ARIA-E in the following 
instances shown in Table AACG.7.2.
If a dosage reduction is required, then the LY3002813 dose will be reduced to the next lower 
dose (from 1400 mg to 700 mg or from 700 mg to placebo).

I5T-MC-AACG(d) Clinical Protocol
Page 52
LY3002813
Table AACG.7.2.
LY3002813 Dosage Modifications for First Occurrence of ARIA-E
ARIA-E 
SYMPTOMS
ARIA-E on MRI
Mild
Moderate
Severe
  No symptoms
Continue on current dosinga
LY3002813
Dose reductiona,b
Temporary Discontinuation
of LY3002813
(refer to Section 8.1.1.1)b
  Mild
LY3002813
Dose reductiona,b
Temporary Discontinuation 
of LY3002813
(refer to Section 8.1.1.1)b
Temporary Discontinuation 
of LY3002813
(refer to Section 8.1.1.1)b
  Moderate
Temporary Discontinuation 
of LY3002813
(refer to Section 8.1.1.1)b
Temporary Discontinuation 
of LY3002813
(refer to Section 8.1.1.1) b
Temporary Discontinuation 
of LY3002813
(refer to Section 8.1.1.1)b
  Severe
Temporary Discontinuation 
of LY3002813
(refer to Section 8.1.1.1)b
Temporary Discontinuation 
of LY3002813
(refer to Section 8.1.1.1)b
Temporary Discontinuation 
of LY3002813
(refer to Section 8.1.1.1)b
a
Investigator may choose to temporarily discontinue LY3002813 after discussion with the sponsor.
b
If the patient has a second incidence of ARIA-E and has previously been dose reduced or temporarily 
discontinued from LY3002813, then LY3002813 will be permanently discontinued (see Section 8.1).
All Cases of ARIA-E will require unscheduled MRI scans every 4-6 weeks until ARIA-E has 
resolved.  Further details are provided in the Operations Manual.
7.4.2. LY3002813 Dosage Modification for ARIA-H
There will be no dose reductions for changes in ARIA-H.  Patients will be discontinued from 
dosing and IV administration if ARIA-H discontinuation rules are met (see Section 8.1).  Patients 
will not be re-challenged with LY3002813 after dose discontinuation for ARIA-H.
All new cases of ARIA-H will require unscheduled MRI scans every 4-6 weeks until ARIA-H 
has stabilized without new findings.
7.5.
Preparation/Handling/Storage/Accountability
The investigator or his/her designee is responsible for the following:

confirming appropriate temperature conditions have been maintained during 
transit for all study treatment received and any discrepancies are reported and 
resolved before use of the study treatment.

ensuring that only participants enrolled in the study may receive study treatment 
and only authorized site staff may supply or administer study treatment.  All study 
treatments must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions 
with access limited to the investigator and authorized site staff.

I5T-MC-AACG(d) Clinical Protocol
Page 53
LY3002813

the investigator, institution, or the head of the medical institution (where 
applicable) is responsible for study treatment accountability, reconciliation, and 
record maintenance (such as receipt, reconciliation and final disposition records).
7.6.
Treatment Compliance
The administration of all study medication should be recorded in the appropriate sections of the 
electronic case report form (eCRF).
7.6.1. LY3002813 Treatment Compliance
Because dosing occurs at study visits, patients who attend all visits and successfully receive 
LY3002813 infusions are automatically compliant with this treatment.  Any infusion at which 
75% (approximately 105 mL) or more of the infusion solution is given will be considered a 
complete infusion.
If a patient attends a visit but does not receive a complete infusion (e.g., due to technical 
complications), every effort should be made to complete the infusion within 24 hours if possible.  
If less than 75% of the infusion solution is given, this must be recorded as an incomplete infusion 
on the CRF.
Missed infusions should be recorded on the CRF.
7.7.
Concomitant Therapy
All concomitant medication taken during the study must be recorded on the Concomitant 
Medication CRF.  Patients and their study partners will be instructed to consult the investigator 
or other appropriate study personnel at the site before initiation of any new medications or 
supplements and before changing dose of any current concomitant medications or supplements.
To ensure standard of care for AD, use of approved treatments for AD is permitted in this study, 
and no medications are explicitly excluded from use.  The section below provides additional 
guidance on managing concomitant medication use.
Allowed Medications.  Use of approved or standard of care treatments for AD is permitted during 
the study, provided that such medications dose has been unchanged for 2 months before Visit 2.  
Doses of these medications should remain constant throughout the double-blind period (Visit 2 
to Visit 21).
If a patient has recently stopped AChEIs and/or memantine, he or she must have discontinued 
treatment at least 2 months before Visit 2.
Other vitamins, medical food, or nutraceuticals given for their possible effects on AD may be 
continued on stable doses beginning 2 months before Visit 2.
Prior to V21, before a patient starts, stops, or changes doses of AChEIs and/or memantine or 
other treatments for their AD, the Sponsor or designee must be contacted to determine 
whether or not the patient should continue in the study and whether or not clinical outcome 
measures should be performed.  Failure to notify Lilly or its designee regarding starting, 

I5T-MC-AACG(d) Clinical Protocol
Page 54
LY3002813
stopping or changing doses of AChEIs and/or memantine or other treatments for their AD
prior to V21 will be considered a protocol deviation.
Nonmedication treatments for AD such as behavioral management are permitted but are subject 
to the same restrictions as medication treatment taken for AD.
Other concomitant medications that affect CNS function may be given if the dose remains 
unchanged throughout the study.  Doses of these compounds should remain constant from 1 
month before screening (Visit 1).
If unforeseen starting, stopping, or changing of stable doses of drugs affecting CNS function 
occurs prior to V21 of the study, Lilly or its designee must be contacted to determine whether or 
not the patient should continue in the study and whether or not outcome measures should be 
performed.  Failure to notify Lilly or its designee regarding starting, stopping or changing 
doses of CNS medications prior to V21 of the study will be considered a protocol deviation.
Use of benzodiazepines for treatment on an as-needed basis for insomnia or daily dosing as
anxiolytics is permitted.  Use of sedatives or hypnotics should be avoided for 8 hours before 
administration of the cognitive and functional tests unless they are given chronically.
If an infusion reaction occurs, rescue medications such as, but not limited to, diphenhydramine, 
epinephrine, and/or methylprednisolone may be administered at the discretion of the investigator.  
Administration of medications before an infusion to prevent a reaction does not cause a 
discontinuation of the patient from the study.  If the need for concomitant medication arises, 
inclusion or continuation of the patient may be at the discretion of the investigator after 
consultation with a Lilly CRP.  Concomitant therapy administered to treat an infusion reaction or 
as premedication for infusions should be documented.
Excluded Medications.
IgG therapy (also known as gamma globulin or intravenous immunoglobulin [IVIG]) is not 
allowed during the study.
7.8.
Treatment after the End of the Study
7.8.1. Treatment after Study Completion
There is no planned open label extension at this time, or plan to otherwise make LY3002813 
available to patients after conclusion of the study.

I5T-MC-AACG(d) Clinical Protocol
Page 55
LY3002813
8. Discontinuation Criteria
8.1.
Discontinuation from Study Treatment
Possible reasons leading to permanent discontinuation of study treatment:

Subject Decision
o
the subject or the subject’s designee; for example, legal guardian requests to 
discontinue investigational product.

Discontinuation due to a hepatic event or liver test abnormality
Subjects who are discontinued from investigational product due to a hepatic event or liver 
test abnormality should have additional hepatic safety data collected via CRF/electronic 
data entry.
Discontinuation of the investigational product for abnormal liver tests should be 
considered by the investigator when a subject meets one of the following conditions after 
consultation with the Lilly-designated medical monitor:
o
alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >8X 
upper limit of normal (ULN)
o
ALT or AST >5X ULN for more than 2 weeks
o
ALT or AST >3X ULN and total bilirubin level (TBL) >2X ULN or 
international normalized ratio (INR) >1.5
o
ALT or AST >3X ULN with the appearance of fatigue, nausea, vomiting, 
right upper-quadrant pain or tenderness, fever, rash, and/or eosinophilia 
(>5%)
o
alkaline phosphatase (ALP) >3X ULN
o
ALP >2.5X ULN and TBL >2X ULN
o
ALP >2.5X ULN with the appearance of fatigue, nausea, vomiting, right 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%)
In addition, subjects will be discontinued from the investigational product in the following 
circumstances:

Treatment with LY3002813 will be permanently discontinued in patients with:
o
a second incidence of ARIA-E after a previous dose reduction or temporary 
discontinuation of LY3002813
o
any increase in ARIA-H accompanied by clinically significant symptoms
o
>4 new microhemorrhages, >1 new area of superficial siderosis or significant 
worsening of pre-existing superficial siderosis, or any macrohemorrhage 
regardless of symptoms
o
an ARIA-E event reported as an SAE, regardless of severity of symptoms or MRI 
findings

I5T-MC-AACG(d) Clinical Protocol
Page 56
LY3002813

Treatment with LY3002813 will also be permanently discontinued in patients with:
o
Prolonged acute infusion reaction (i.e., not responsive to medication such 
as antihistamines, nonsteroidal anti-inflammatory drugs, and/or narcotics 
and/or brief interruption of infusion).
o
Adverse event or clinically significant laboratory value, ECG result, physical 
examination finding, MRI finding (such as symptomatic ischemic stroke), 
C-SSRS result, or vital sign measurement of such severity that, in the opinion of 
the investigator or Lilly-designated medical monitor, continued treatment is not in 
the best interest of the patient.
o
Severe non-compliance to the study protocol that results in a safety concern, in 
the judgment of the investigator.
o
The patient, for any reason, requires a treatment with an excluded therapeutic 
agent and temporary discontinuation criteria cannot be met (see Section 8.1.1.2).
Patients may permanently discontinue study treatment and remain in the trial.  If LY3002813 
infusion is permanently discontinued but the patient remains in the study, one PK sample should 
be collected at the soonest scheduled visit regardless if serum LY3002813 is on the Schedule of 
Activities at that visit. Dosing dates and times should be collected.  Subsequent PK sample 
collection should follow the protocol Schedule of Activities for serum LY3002813 collection 
unless the scheduled visit exceeds 6 months since discontinuation of infusions. No additional 
serum collection for LY3002813 is required once the patient exceeds 6 months since 
discontinuation of LY3002813 infusions.
Subjects permanently discontinuing from the study prematurely for any reason should complete 
AE and other follow-up procedures per Section 2 (Schedule of Activities), Section 9.2 (Adverse 
Events), and Section 9.4 (Safety) of this protocol.
8.1.1. Temporary Discontinuation from Study Treatment
8.1.1.1.
Temporary Discontinuation from LY3002813 Study Treatment Due to 
ARIA-E
Temporary discontinuation from LY3002813 treatment is allowed for ARIA-E if the ARIA-E 
meets the temporary discontinuation criteria shown in Table AACG.7.2.
In cases of ARIA-E where the protocol indicates continued dosing or a dose reduction rather 
than temporary discontinuation (see Table AACG.7.2), the investigator may choose to 
temporarily discontinue LY3002813 after discussion with the sponsor. This will require 
choosing not to dispense LY3002813 through IWRS at relevant visits.
Study drug (LY3002813) may be restarted following a first incidence of ARIA-E at the 
discretion of the investigator if dosing is temporarily discontinued due to ARIA-E and there is 
complete resolution of symptoms and radiologic findings within 16 weeks after the temporary 
drug discontinuation.
If ARIA-E symptoms and radiologic findings have not completely resolved within 16 weeks, 
then the patient will be permanently discontinued from LY3002813 treatment.

I5T-MC-AACG(d) Clinical Protocol
Page 57
LY3002813
Study drug may be restarted at either 700 mg or placebo, double blinded, depending on the 
original study arm to which the patient is randomized.
An unscheduled safety MRI scan will be required 4-6 weeks after dose restarts.
8.1.1.2.
Temporary Discontinuation from LY3002813 Study Treatment for 
Reasons Other than ARIA-E
Temporary discontinuation from LY3002813 treatment is allowed if a short-term treatment of an 
excluded medication is necessary, secondary to hospitalization, personal circumstances or to 
evaluate the study drug impact on an uncertain AE.  Study drug may be restarted at the 
investigator’s discretion.  If temporary discontinuation is due to an AE, it should be reported to 
the Lilly CRP.  Temporary treatment discontinuation and re-starting should be documented.  
Restarting treatment after a discontinuation period that is greater than 12 weeks should be 
discussed between the investigator and Lilly CRP.
8.1.2. Discontinuation of Inadvertently Enrolled Subjects
If the sponsor or investigator identify a subject who did not meet enrollment criteria and was 
inadvertently enrolled, then the subject should be discontinued from study treatment unless there 
are extenuating circumstances that make it medically necessary for the subject to continue on 
study treatment.  If the investigator and the sponsor CRP/CRS agree it is medically appropriate 
to continue, the investigator must obtain documented approval from the sponsor CRP/CRS to 
allow the inadvertently enrolled subject to continue in the study with or without treatment with 
investigational product.
Safety follow-up is as outlined in Section 2 (Schedule of Activities), Section 9.2 (Adverse 
Events) and Section 9.4 (Safety) of this protocol.
8.2.
Discontinuation from the Study
Patients who do not meet entry criteria or who are excluded by exclusion criteria from Visit 1 
tests and procedures should be discontinued from the study before randomization as an entry 
failure.
Patients who exhibit any of the following conditions during the study that may possibly be 
related to study drug will be discontinued from the study, but will be encouraged to undergo final 
assessment visits and procedures as outlined in the Schedule of Activities (Section 2):

Patients who require a ferromagnetic implant or insertion of a cardiac pacemaker 
that is not MRI-compatible will be discontinued from study drug and from the 
study; and, with the exception of an MRI, should have end-of-therapy and/or end-
of-study procedures performed as shown in the Schedule of Activities (Section 2).
Subjects will also be discontinued from the study in the following circumstances:

enrollment in any other clinical study involving an investigational product or enrollment 
in any other type of medical research judged by sponsor not to be scientifically or 
medically compatible with this study

I5T-MC-AACG(d) Clinical Protocol
Page 58
LY3002813

participation in the study needs to be stopped for medical, safety, regulatory, or other 
reasons consistent with applicable laws, regulations, and good clinical practice (GCP)

investigator decision
o
the investigator decides that the subject should be discontinued from the study
o
if the subject, for any reason, requires treatment with another therapeutic agent 
that has been demonstrated to be effective for treatment of the study indication, 
discontinuation from the study occurs prior to introduction of the new agent

subject decision
o
the subject or the subject’s legal representative requests to be withdrawn from the 
study
Subjects discontinuing from the study prematurely for any reason must complete AE and other 
safety follow-up per Section 2 (Schedule of Activities), Section 9.2 (Adverse Events), and 
Section 9.4 (Safety) of this protocol. In addition, subjects discontinuing from the study 
prematurely should be encouraged to return to the site beginning 12 weeks after their ED visit for 
immunogenicity and safety assessments (Visits 801 through 804, as described in Section 5.1.3).
8.3.
Lost to Follow-Up
A subject will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site.  Site personnel are expected to make 
diligent attempts to contact subjects who fail to return for a scheduled visit or who were 
otherwise unable to be followed up by the site.
Site personnel, or an independent third party, will attempt to collect the vital status of the subject 
within legal and ethical boundaries for all subjects randomized, including those who did not get 
investigational product.  Public sources may be searched for vital status information.  If vital 
status is determined, this will be documented and the subject will not be considered lost to 
follow-up.
Lilly personnel will not be involved in any attempts to collect vital status information.

I5T-MC-AACG(d) Clinical Protocol
Page 59
LY3002813
9. Study Assessments and Procedures
Section 2 lists the Schedule of Activities, with the study procedures and their timing (including 
tolerance limits for timing).
Appendix 2 lists the clinical laboratory tests that will be performed for this study.
Unless otherwise stated in the subsections below, all samples collected for specified laboratory 
tests will be destroyed within 60 days of receipt of confirmed test results.  Certain samples may 
be retained for a longer period, if necessary, to comply with applicable laws, regulations, or 
laboratory certification standards.
9.1.
Efficacy Assessments
Screening measures used for diagnosis and establishment of study eligibility are described 
elsewhere (Section 5.1.1.1).
Cognitive and functional testing will be administered using an eCOA tablet.  The audio voice 
recordings of the rater’s questions and the patient’s and study partner’s responses will also be
collected via the eCOA tablet during administration of the cognitive and functional testing for 
central monitoring of rater scale administration (Appendix 3, 3.2.1).  Cognitive and functional 
testing for each patient should be performed at approximately the same time on each day that 
testing occurs to reduce potential variability.  Note that the ADAS-Cog and MMSE must be 
administered by a different rater than the ADCS-ADL and CDR.  These 2 raters should continue 
doing the same scale with the same patient throughout the study.  If possible, each assessment 
should be performed on a given patient by the same rater at each visit.  The principal investigator 
(PI) has the responsibility of selecting the raters who will administer the instruments at the site, 
as long as all training requirements have been met by those raters (Appendix 3, 3.1.5).
When administered, cognitive and functional testing should be performed first, before medical 
procedures that could be stressful for the patient (e.g., blood draws).  Note that some procedures 
(MRI, flortaucipir F18 PET tau imaging, florbetapir F18 PET amyloid imaging) can be 
conducted on other days within the visit window.
9.1.1. Primary Efficacy Assessments
Integrated Alzheimer’s Disease Rating Scale (iADRS; Wessels et al. 2015).  The iADRS 
represents a composite that was developed using both a theory-driven approach (incorporating 
measures of both cognition and function) and a data-mining approach (identifying the most 
sensitive combination of scales through analysis of data from the Alzheimer’s Disease 
Neuroimaging Initiative and the LY2062430 EXPEDITION, EXPEDITION2, and 
EXPEDITION3 studies).  The iADRS is a simple linear combination of scores from 2 well-
established, therapeutically sensitive, widely accepted measures in AD, the ADAS-Cog13 and the 
ADCS-iADL, measuring the core domains of AD.  All items of these 2 scales are included 
without additional weighting of items, yielding face validity and ease of interpretation of the 
composite relative to its components.

I5T-MC-AACG(d) Clinical Protocol
Page 60
LY3002813
The iADRS score will be derived from the ADAS-Cog13 and the ADCS-iADL and will be the 
primary efficacy measure.  The ADAS-Cog13 and the ADCS-ADL will be the actual scales 
administered to patients.
9.1.2. Secondary Efficacy Assessments
Additional clinical outcome measures should be administered in the same order at every visit, 
immediately following assessment of the ADAS-Cog13.  To minimize missing data, the rater 
should include each measure orally with the patient or study partner (as designated in 
instructions), recording responses appropriately.  The same study partner should be used as the 
informant at all visits.
9.1.2.1.
Alzheimer’s Disease Assessment Scale—Cognitive subscale 
(ADAS-Cog13)
The ADAS-Cog13 is a rater-administered instrument that was designed to assess the severity of 
the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD 
(Rosen et al. 1984).  The ADAS-Cog13 should be administered by the same rater from visit to 
visit to reduce potential variability.  The cognitive subscale of the ADAS, the ADAS-Cog13, 
consists of 13 items assessing areas of cognitive function most typically impaired in AD:  
orientation, verbal memory, language, praxis, delayed free recall, digit cancellation, and maze-
completion measures (Mohs et al. 1997).  The ADAS-Cog13 allows better discrimination of 
differences among mild patients than the ADAS-Cog11, which will be included as a secondary 
outcome.  The ADAS-Cog13 scale ranges from 0 to 85, with higher scores indicating greater 
disease severity.
9.1.2.2.
Alzheimer’s Disease Cooperative Study—Activities of Daily Living 
Inventory (ADCS-ADL)
The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire that is to 
be answered by the patient’s study partner (Galasko et al. 1997, 2004).  The ADCS-ADL should 
be administered by the same rater from visit to visit to reduce potential variability.  The ADCS-
ADL subset of items (items 7 to 23) for instrumental activities of daily living (ADCS-iADL) will 
be used as a secondary efficacy measure.  The focus in the early symptomatic AD population is 
on the instrumental activities of daily living (iADLs) rather than the basic activities of daily 
living (bADLs), which are thought to be affected in more severe stages of the disease.  The range 
for the iADL score is 0 to 56, with lower scores indicating greater disease severity.  For each of 
the specific items, the study partner is first asked if the patient attempted the ADL during the past 
4 weeks.  If the patient did attempt the ADL, the study partner is asked to rate the patient’s 
performance level based on a set of performance descriptions.  Scores for each item and the 
overall score for the tool are calculated.  The range for the total ADCS-ADL score is 0 to 78, 
with higher scores indicating greater level of impairment.  Separate scores for the bADLs (0 to 
22) will also be computed.

I5T-MC-AACG(d) Clinical Protocol
Page 61
LY3002813
9.1.2.3.
Clinical Dementia Rating Scale (CDR-SB)
The CDR is a semi-structured interview performed with the patient and study partner (informant) 
that provides an index of global functioning (Berg e al. 1992).  The CDR should be administered 
by the same rater from visit to visit to reduce potential variability.  The informant is queried 
about the patient’s memory, orientation, judgment and problem solving, community affairs, 
home and hobbies, and personal care.  The patient’s memory, orientation, judgment, and 
problem-solving ability are assessed.  Higher scores indicate greater disease severity.  By 
assigning a severity score for each of the 6 domains, a total score known as sum of boxes is 
obtained—hence the abbreviation, CDR-SB.
9.1.2.4.
Mini-Mental State Examination (MMSE)
The MMSE is a brief instrument used to assess cognitive function in patients (Folstein et al. 
1975).  The MMSE should be administered by the same rater from visit to visit to reduce 
potential variability.  The instrument is divided into 2 sections.  The first section measures 
orientation, memory, and attention.  The maximum score for the first section is 21.  The second 
section tests the ability of the patient to name objects, follow verbal and written commands, write 
a sentence, and copy figures.  The maximum score for the second section is 9.  The range for the 
total MMSE score is 0 to 30, with lower scores indicating great level of impairment.
9.1.3. Biomarker Efficacy Measures (Double-Blind Period)
Florbetapir F18 PET scan.  Change in amyloid burden (as assessed by florbetapir F18 PET 
signal) will be compared in LY3002813- and placebo-treated patients for those patients who 
undergo florbetapir F18 PET scans at baseline, Week 52 [Visit 15], and Week 76 [Visit 21] or 
ED) as described in the Schedule of Activities (Section 2).
Flortaucipir F18 PET scan.  Change in tau burden (as assessed by flortaucipir F18 PET signal) 
will be compared in LY3002813- and placebo-treated patients for those patients who undergo 
both baseline and endpoint (Visit 21 [Week 76] or ED) flortaucipir F18 scans as described in the 
Schedule of Activities (Section 2).
Volumetric MRI.  Magnetic resonance imaging of the brain will be performed according to the 
Schedule of Activities (Section 2). LY3002813- and placebo-treatment effects on volumetric 
MRI will be assessed and compared to evaluate the loss of brain volume that occurs in AD 
patients.
9.1.4. Appropriateness of Efficacy Assessments
The iADRS, the primary efficacy measure, is a simple linear combination of scores from 2 
well-established, therapeutically sensitive, widely accepted measures in AD, the ADAS-Cog13 
and the ADCS-iADL, measuring the core domains of AD.  It represents a composite that was 
developed using both a theory-driven approach (incorporating measures of both cognition and 
function) and a data-mining approach (identifying the most sensitive combination of scales 
through analysis of data from the Alzheimer’s Disease Neuroimaging Initiative and the 
LY2062430 EXPEDITION, EXPEDITION2, and EXPEDITION3 studies).  Composite 
endpoints have been increasingly used as primary endpoints in clinical trials (Freemantle et al. 

I5T-MC-AACG(d) Clinical Protocol
Page 62
LY3002813
2003).  Liu-Seifert et al. (2017) demonstrated that the treatment effect size of the iADRS 
composite is greater than the minimum treatment effect size of its components and that above 
certain thresholds of correlations of components and ratios of component effect sizes, the 
composite may outperform its components.
The secondary efficacy measures described in Section 9.1.2 are established measures of 
cognitive and functional outcomes, as well as behavioral symptoms associated with AD 
dementia, and considered appropriate assessments for the early symptomatic AD population.
In addition, the primary target engagement outcome is the reduction of cerebral amyloid as 
measured by quantitative amyloid PET imaging (florbetapir F18 PET SUVr) assessed at 
baseline, 24 weeks, 52 weeks and at 76 weeks after starting treatment.  The postbaseline amyloid 
PET scans are aimed to assess the time course of amyloid reduction and sustainability of amyloid 
reduction.  Reduction of paired helical filaments of cortical tau will be quantitatively assessed by 
tau PET imaging at baseline and 76 weeks.
9.2.
Adverse Events
Investigators are responsible for monitoring the safety of patients who have entered this study 
and for alerting Lilly or its designee to any event that seems unusual, even if this event may be 
considered an unanticipated benefit to the patient.
The investigator is responsible for the appropriate medical care of patients during the study.
Investigators must document their review of each laboratory safety report.
The investigator remains responsible for following, through an appropriate health care option, 
AEs that are serious or otherwise medically important, considered related to the investigational 
product or the study, or that caused the patient to discontinue the investigational product before 
completing the study.  The patient should be followed until the event resolves, stabilizes with 
appropriate diagnostic evaluation, or is reasonably explained.  The frequency of follow-up 
evaluations of the AE is left to the discretion of the investigator.
Lack of drug effect is not an AE in clinical studies, because the purpose of the clinical study is to 
establish treatment effect.
After the informed consent form (ICF) is signed, study site personnel will record via 
CRF/electronic data entry the occurrence and nature of each patient’s preexisting conditions, 
including clinically significant signs and symptoms of the disease under treatment in the study.  
In addition, site personnel will record any change in the condition(s) and any new conditions as 
AEs. Investigators should record their assessment of the potential relatedness of each AE to 
protocol procedure, investigational product, including radiopharmaceutical tracers, via 
CRF/electronic data entry.
The investigator will interpret and document whether or not an AE has a reasonable possibility 
of being related to study treatment, study device, or a study procedure, taking into account the 
disease, concomitant treatment or pathologies.

I5T-MC-AACG(d) Clinical Protocol
Page 63
LY3002813
A “reasonable possibility” means that there is a cause and effect relationship between the 
investigational product, study device and/or study procedure and the AE.
The investigator answers yes/no when making this assessment.
Planned surgeries and nonsurgical interventions should not be reported as AEs unless the 
underlying medical condition has worsened during the course of the study.
If a patient’s investigational product is discontinued as a result of an AE, study site personnel 
must report this to Lilly or its designee via CRF/electronic data entry, clarifying if possible, the 
circumstances leading to any dosage modifications, or discontinuations of treatment.
9.2.1. Serious Adverse Events
An SAE is any AE from this study that results in one of the following outcomes:

death

initial or prolonged inpatient hospitalization

a life-threatening experience (i.e., immediate risk of dying)

persistent or significant disability/incapacity

congenital anomaly/birth defect

important medical events that may not be immediately life-threatening or result in 
death or hospitalization but may jeopardize the patient or may require intervention 
to prevent one of the other outcomes listed in the definition above.  Examples of 
such medical events include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias or convulsions that do not 
result in inpatient hospitalization, or the development of drug dependency or drug 
abuse.
All AEs occurring after signing the ICF are recorded in the CRF/electronic data entry and 
assessed for serious criteria.  The SAE reporting to the sponsor begins after the patient has 
signed the ICF and has received investigational product, including radiopharmaceutical tracers.  
However, if an SAE occurs after signing the ICF, but prior to receiving investigational product, 
the SAE should be reported to the sponsor as per SAE reporting requirements and timelines (see 
Section 9.2) if it is considered reasonably possibly related to study procedure.
Study site personnel must alert Lilly or its designee of any SAE within 24 hours of investigator 
awareness of the event via a sponsor-approved method.  If alerts are issued via telephone, they 
are to be immediately followed with official notification on study-specific SAE forms.  This 24-
hour notification requirement refers to the initial SAE information and all follow-up SAE 
information. Patients with a serious hepatic AE should have additional data collected using the 
CRF/electronic data entry.
Pregnancy (during maternal or paternal exposure to investigational product) does not meet the 
definition of an AE.  However, to fulfill regulatory requirements any pregnancy should be 
reported following the SAE process to collect data on the outcome for both mother and fetus.

I5T-MC-AACG(d) Clinical Protocol
Page 64
LY3002813
Investigators are not obligated to actively seek AEs or SAEs in subjects once they have 
discontinued and/or completed the study (the patient disposition CRF has been completed).  
However, if the investigator learns of any SAE, including a death, at any time after a subject has 
been discharged from the study, and he/she considers the event reasonably possibly related to the 
study treatment or study participation, the investigator must promptly notify Lilly.
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions
Suspected unexpected serious adverse reactions (SUSARs) are serious events that are not listed 
in the IB and that the investigator identifies as related to investigational product or procedure.  
United States 21 CFR 312.32 and European Union Clinical Trial Directive 2001/20/EC and the 
associated detailed guidances or national regulatory requirements in participating countries 
require the reporting of SUSARs.  Lilly has procedures that will be followed for the 
identification, recording and expedited reporting of SUSARs that are consistent with global 
regulations and the associated detailed guidances.
9.2.1.2.
Adverse Events of Special Interest
Specific safety topics of interest for this study include, but are not limited to, the following:

ARIA-E

ARIA-H

Hypersensitivity (immediate and non-immediate), including infusion-related 
reactions

Peripheral nervous system, central nervous system and muscle effects
The topics listed above, as well as other topics which may be subsequently determined by the 
sponsor, will be subject to enhanced surveillance activities.  Additionally, the topics above will 
be analyzed for presentation in the Clinical Study Report in accordance with the Statistical 
Analysis Plan.
9.2.2. Complaint Handling
Lilly collects product complaints on investigational products and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and to 
facilitate process and product improvements.
Patients will be instructed to contact the investigator as soon as possible if he or she has a 
complaint or problem with the investigational product so that the situation can be assessed.
9.3.
Treatment of Overdose
There is no known antidote to LY3002813.  In case of overdose, use appropriate monitoring and 
supportive therapy.

I5T-MC-AACG(d) Clinical Protocol
Page 65
LY3002813
9.4.
Safety
9.4.1. Physical and Neurological Examinations
Complete physical examinations will be performed at screening, baseline, and Weeks 12, 24, 52, 
76, and ED as indicated in the Schedule of Activities (Section 2).  Brief physical examinations 
will be performed at Weeks 36 and 64.  The complete physical examination will include 
assessment of the following:  general appearance; skin, head and neck; lymph nodes; thyroid; 
abdomen (bowel sounds, liver and spleen palpation); back (costovertebral angle tenderness); and 
musculoskeletal, cardiovascular, and respiratory systems.  The brief physical examination will 
include assessments of the skin, lungs, cardiovascular system, and abdomen (bowel sounds, liver 
and spleen palpation).
Complete neurological examinations will be performed as indicated in the Schedule of Activities 
(Section 2).  The examinations will include a thorough assessment of gait, balance, coordination, 
cranial nerves, sensory and motor systems, and reflexes.  If necessary given the training of the 
principal investigator, a neurologist will be consulted in the event of significant new findings.
If a clinically meaningful change in an MRI is noted during the study, an additional full 
neurological exam will be performed as soon as possible, along with any other medical follow-
up deemed necessary by the investigator.
9.4.2. Electrocardiograms
For each patient, 12-lead digital ECGs will be collected as triplicates during the double-blind 
period according to the Schedule of Activities (Section 2).  Patients must be supine for 
approximately 5 to 10 minutes before ECG collection and remain supine but awake during ECG 
collection.
Consecutive replicate ECGs will be obtained at approximately 1-minute intervals.  
Electrocardiograms may be obtained at additional times, when deemed clinically necessary.  
Collection of more ECGs (more replicates) than expected at a particular time point is allowed 
when needed to ensure high-quality records.
Electrocardiograms will initially be interpreted by a qualified physician (the investigator or 
qualified designee) at the site as soon after the time of ECG collection as possible, and ideally 
while the patient is still present, to determine whether the subject meets entry criteria at the 
relevant visit(s) and for immediate patient management, should any clinically relevant findings 
be identified.
After enrollment, if a clinically significant increase in the QT/corrected QT (QTc) interval from 
baseline or other clinically significant quantitative or qualitative change from baseline is 
identified, the patient will be assessed by the investigator for symptoms (e.g., palpitations, near 
syncope, syncope) and to determine whether the patient can continue in the study.  The 
investigator or qualified designee is responsible for determining if any change in patient 
management is needed.  The investigator or qualified designee must document his/her review of 

I5T-MC-AACG(d) Clinical Protocol
Page 66
LY3002813
the ECG printed at the time of evaluation from at least 1 of the replicate ECGs from each time 
point.
All digital ECGs will be electronically transmitted to a designated central ECG laboratory.  A
cardiologist at the central ECG laboratory will then conduct a full overread on 1 of the replicates 
(including all intervals).  A report based on data from this overread will be issued to the 
investigative site.  For each set of replicates, the cardiologist will determine the RR and QT 
intervals, and heart rate on the ECGs that were not fully overread.  These data are not routinely 
reported back to the investigative site.  All data from the overreads will be placed in the Lilly 
database for analytical and study report purposes.
When there are differences in ECG interpretation between the investigator (or qualified 
designee) and the cardiologist at the central ECG laboratory, the investigator’s (or qualified 
designee’s) interpretation will be used for study entry and immediate patient management.  
Interpretations from the cardiologist at the central ECG laboratory will be used for data analysis 
and report writing purposes.
The investigator (or qualified designee) must document his/her review of 1 of the replicate ECGs 
printed at the time of collection, the final overread ECG report issued by the central ECG 
laboratory, and any alert reports.
9.4.3. Vital Signs
Vital signs, including temperature, will be measured at all visits.
9.4.3.1.
Blood Pressure
Sitting blood pressure and pulse will be measured after 5 minutes in the sitting position at all
visits.  In addition, orthostatic blood pressure and pulse will be measured supine and standing at 
designated visits, as detailed in the Schedule of Activities (Section 2).
Orthostatic Blood Pressure Monitoring:  For orthostatic blood pressure monitoring, subjects 
should be supine for at least 5 minutes and stand for at least 3 minutes prior to taking the 
respective measurements.  If the subject feels unable to stand, only supine vital signs will be 
recorded.
Unscheduled orthostatic vital signs should be assessed, if possible, during any AE of dizziness or 
posture-induced symptoms.
Any clinically significant findings from vital signs measurement that result in a diagnosis and 
that occur after the patient receives the first dose of study treatment should be reported to Lilly or 
its designee as an AE via CRF/electronic data entry.
9.4.3.2.
Height, Weight, and Body Temperature
Height and body weight will be measured.  Measurements should be taken without shoes and, 
when possible, the same scale should be used for all measurements.  Body mass index (BMI) 
will be calculated from the height and body weight.  Temperature will be recorded using an oral 
or tympanic (or other acceptable route) thermometer.

I5T-MC-AACG(d) Clinical Protocol
Page 67
LY3002813
Body weight will be collected on the laboratory requisition for creatinine clearance calculations.  
Any body weight data entered into the eCRF will be used for the overall data analysis.
9.4.4. Laboratory Tests
For each patient, laboratory tests detailed in (Appendix 2) should be conducted according to the 
Schedule of Activities (Section 2).
With the exception of laboratory test results that may unblind the study, Lilly or its designee will 
provide the investigator with the results of laboratory tests analyzed by a central vendor, if a 
central vendor is used for the clinical trial.
Any clinically significant findings from laboratory tests that result in a diagnosis and that occur 
after the patient receives the first dose of investigational product should be reported to Lilly or its 
designee as an AE via CRF/electronic data entry.
9.4.5. Immunogenicity Assessments
Where local regulations and ERBs allow, at the visits and times specified in the Schedule of 
Activities (Section 2), venous blood samples of approximately 10 mL each will be collected to 
determine antibody production against LY3002813.  To interpret the results of immunogenicity, 
a venous blood sample will be collected, if warranted, at the same time points to determine the 
serum concentrations of LY3002813.  All samples for immunogenicity should be taken predose 
when applicable and possible.
Immunogenicity will be assessed by a validated assay designed to detect ADAs in the presence 
of LY3002813 at a laboratory approved by the sponsor.  Antibodies may be further characterized 
and/or evaluated for their ability to neutralize the activity of LY3002813.  The testing paradigm 
is outlined in Section 10.3.4.6.
Samples will be retained for a maximum of 15 years after the last patient visit, or for a shorter 
period if local regulations and ERBs allow, at a facility selected by the sponsor.  The duration 
allows the sponsor to respond to future regulatory requests related to LY3002813.  Any samples 
remaining after 15 years will be destroyed.
9.4.6. Other Tests
9.4.6.1.
Columbia Suicide Severity Rating Scale – Adult Version
Consistent with Food and Drug Administration (FDA) regulatory guidance (FDA 2012), any 
occurrence of suicide-related thoughts and behaviors will be assessed as indicated in the 
Schedule of Activities (Section 2).  The C-SSRS is a scale that captures the occurrence, severity, 
and frequency of suicide-related thoughts and behaviors during the corresponding assessment 
period.  The scale includes suggested questions to elicit the type of information needed to 
determine if a suicide-related thought or behavior occurred.
The first time the scale is administered in this study, the C-SSRS “Baseline” version will be 
used, and the findings will constitute the baseline assessment.  The C-SSRS “Since Last Visit” 
scale will be used for all subsequent assessments.

I5T-MC-AACG(d) Clinical Protocol
Page 68
LY3002813
The C-SSRS will be administered to the patient with the study partner/study informant present or 
available by telephone, after the cognitive and functional assessments.  Responses from both the 
study partner/study informant and patient will be considered when administering the scale.  If a 
suicide-related thought or behavior is identified at any time during the study, a thorough 
evaluation will be performed by a study physician, and appropriate medical care will be 
provided.
The Lilly Self-Harm Supplement should be completed every time the C-SSRS is administered.  
If, based on administration of the C-SSRS, it is determined that suicide-related behaviors have 
occurred, then the Lilly Self-Harm Follow-Up form will be used to collect additional information 
to allow for a more complete assessment of these behaviors.
9.4.6.2.
Magnetic Resonance Imaging
Magnetic resonance imaging of the brain will be performed according to the Schedule of 
Activities (Section 2) and as clinically indicated.  This technology will be used to check for 
evidence of ARIA-H or ARIA-E, and other clinically relevant inclusion/exclusion and safety 
findings (The MRI data will also be used to calculate brain volumes, as noted in Section 9.1.3).
The MRI scans will be reviewed by the investigator or qualified designee for immediate patient 
management.  Any clinically significant findings noted at baseline that result in a diagnosis 
should be recorded as a preexisting condition or AE.  After the MRI scan is read locally, the MRI 
scans will be sent for analysis to a centralized MRI vendor designated by Lilly.  Final MRI 
eligibility at screening will be determined by the centralized MRI vendor designated by Lilly and 
the MRI results will be reported to the site as “does” or “does not” meet MRI eligibility criteria.  
Specific analyses of the scans including assessments of ARIA-H and ARIA-E and calculations of 
brain volumes will be interpreted by the centralized MRI vendor for data analysis and report-
writing purposes.  Results of centrally read MRIs regarding patient care/safety will be reported 
back to sites.
9.4.6.3.
Ophthalmological Examination
While the BACE inhibitor LY3202626 is no longer being administered in this study (see 
Section 5.1), ophthalmological examinations in patients who previously received LY3202626 or 
oral placebo will be performed at the next scheduled examination time point after their final dose 
of oral study medication (see the Schedule of Activities [Section 2]).  Patients who received 
LY3202626/oral placebo after their Visit 9 ophthalmological examination are to have an 
unscheduled ophthalmological examination at the next available opportunity.  Patients screened 
or randomized under the current amendment are not required to undergo any ophthalmological
examinations at baseline or any other study visits.
Patients who previously received LY3202626 or oral placebo will undergo comprehensive 
ophthalmological examinations performed by an ophthalmologist or optometrist (where 
permitted by law) to assess visual function and morphology.  Scheduled examinations will 
include the following:  visual acuity, intraocular pressure, dilated funduscopic exam (dilation 
only performed in patients without contraindication to mydriatics), slit lamp exam, color 
photography of the retina, and optical coherence tomography (OCT) or equivalent; examinations 

I5T-MC-AACG(d) Clinical Protocol
Page 69
LY3002813
will also include color vision assessment.  Assessments will preferably be performed by the same 
ophthalmologist or optometrist for each patient’s visit.  Patients who complain of vision 
disturbance, such as change in field of vision, color, acuity or anything potentially localizable to 
the retina, during the clinical trial should be referred to the ophthalmologist or optometrist 
(where permitted by law) for unscheduled evaluation.
Data from the ophthalmological examination visits will be provided from the local 
ophthalmologist or optometrist to the investigator.
The local ophthalmologist or optometrist will review the color photography and OCT to aid in 
immediate patient management.  Additionally, the color photography of retina and OCT will be 
analyzed by a central reader.
Unblinded results of the eye safety data will be reviewed by the DMC.
Any clinically significant findings that result in a diagnosis should be reported to Lilly or its 
designee as a pre-existing condition or AE via eCRF per Section 9.2.  The PI will make all final 
determinations of AEs in consultation with performing eye examiner, if applicable.
9.4.6.4.
Dermatological Examination
While the BACE inhibitor LY3202626 is no longer being administered in this study, complete 
dermatological examinations in patients who previously received LY3202626 or oral placebo 
will be performed at the next scheduled examination time point after their final dose of oral study 
medication (see the Schedule of Activities [Section 2]). Patients who received LY3202626/oral 
placebo after their Visit 8 dermatological examination are to have an unscheduled dermatological 
examination at the next available opportunity.  Patients screened or randomized under the current 
amendment are not required to undergo any skin exams at baseline or any other study visits.
This examination will preferably be performed by the same dermatologist for each patient’s visit.  
All dermatological examinations must be performed by a dermatologist who will inspect the 
patient’s unclothed full body using an ultraviolet (UV) light.  The initial examination will 
include Fitzpatrick skin-type classification scale.
At each examination, abnormal hypopigmentation will be assessed by location, percentage of 
body surface area involvement, degree (partial/decreased pigmentation to complete 
depigmentation), and other findings in or around the hypopigmented area (such as redness or 
induration).  A static physician’s global assessment (sPGA) will be used to determine the 
patient’s overall hypopigmentation severity at a given time point using a visual analog scale 
(VAS) ranging from 0 to 100.  In addition, patients noted to have evidence of hypopigmentation 
will be asked to record how bothersome they find the hypopigmentation on a VAS ranging from 
0 to 100.  Skin photographs may be taken as appropriate for generating supporting 
documentation, but not for the purpose of primary clinical dermatologic evaluation or for data 
generation or analysis.  A punch biopsy may be obtained at the discretion of the dermatologist.
Unblinded results of the dermatological safety data will be reviewed by the DMC.

I5T-MC-AACG(d) Clinical Protocol
Page 70
LY3002813
Any clinically significant findings that result in a diagnosis should be reported to Lilly or its 
designee as a pre-existing condition or AE via eCRF per Section 9.2.  The PI will make all final 
determinations of AEs in consultation with the dermatologist.
9.4.7. Safety Monitoring
Lilly will periodically review evolving aggregate safety data within the study by appropriate 
methods.
In the event that safety monitoring uncovers an issue that needs to be addressed by unblinding at 
the group level, only members of the data monitoring board (an advisory group for this study 
formed to protect the integrity of data; refer to Interim Analyses section [Section 10.3.6]) can 
conduct additional analyses of the safety data.
Lilly will review SAEs within time frames mandated by company procedures.  The Lilly clinical 
research physician or scientist will, as appropriate, consult with the functionally independent 
Global Patient Safety therapeutic area physician or clinical scientist, and periodically review:

trends in safety data

laboratory analytes including blood hematology, chemistry, and urinalysis

AEs including monitoring of hypersensitivity and infusion reactions, AEs 
associated with anti-LY3002813 antibodies (immunogenicity), ARIA-H, 
ARIA-E, ECG findings, neurological findings, hemorrhagic stroke, 
microhemorrhage (cerebral microhemorrhage, cerebellar microhemorrhage, brain 
stem microhemorrhage) as identified by investigator, and suicide-related thoughts 
and behaviors.
9.4.7.1.
LY3002813 Hypersensitivity (Immediate and Non-immediate), Including 
Infusion-Related Reactions
9.4.7.1.1. Premedication for Infusions
Premedication for dosing is not planned.  However, if an infusion reaction occurs, appropriate 
medication may be used as determined by the study investigators (see Section 7.7).  The patient 
may be premedicated for subsequent infusions.  If infusion reactions are observed, but review of 
the data suggests that dosing may continue, administration of medicines such as acetaminophen 
(500 to 1000 mg) and/or an antihistamine, and/or methylprednisolone (or other corticosteroid) 
may be administered before starting subsequent infusions at the discretion of the investigator.  
Any premedication given will be documented as a concomitant therapy (see Section 7.7).
9.4.7.1.2. Management of Infusion Reactions
There is a risk of an infusion reaction with any biological agent; therefore, all patients should be 
monitored closely.  Symptoms and signs that may occur as part of an infusion reaction include, 
but are not limited to, fever, chills, nausea, headache, bronchospasm, hypotension, angioedema, 
throat irritation, rash, pruritus, myalgia, and dizziness.  In the event that an infusion reaction 
occurs, the following guidance should be followed:

I5T-MC-AACG(d) Clinical Protocol
Page 71
LY3002813

the investigational product infusion should be slowed or stopped, depending on the 
symptoms/signs present

if slowed, the infusion should be completed at the slower rate, as tolerated and 
documented in the CRF

if stopped, no further attempts to administer the investigational product will be made, and 
this will be documented in the CRF

supportive care should be employed in accordance with the symptoms/signs.
Management of the infusion reaction should proceed according to the severity of the reaction as 
per the flowchart in the Manual of Operations.  This may include, but is not limited to, rescue 
medications such as diphenhydramine, epinephrine, and/or methylprednisolone.
Additional data should also be collected via the CRF/electronic data entry. Please see the 
Operations Manual for more detail.
Additional, unscheduled stored serum samples for possible immune safety laboratory testing 
(including but not limited to β tryptase, total immunoglobulin E, and immune complex testing) 
should also be collected as close to the onset of the event as possible, but within 120 minutes,
and 4-6 weeks after moderate or severe infusion reactions.
9.4.7.2.
LY3002813 Immunogenicity
Patients are to return to the site for immunogenicity and safety follow-up visits (Visit 801
through Visit 804) beginning at Week 88 (or 12 weeks after their last dose of LY3002813) for 
collection of blood samples for anti-drug antibody (ADA; anti-LY3002813 antibody) and PK
measurement, assessment of adverse events, C-SSRS, concomitant medications, and vital signs. 
The results of ADA testing remain blinded.
In order to preserve the blind, patients will need to complete Visits 801 through 804 until all 
patients in the trial have reached Visit 21 and datalock for the treatment period has been 
achieved. After datalock, the central laboratory will notify the sites and sponsor (or designee) as 
to whether a patient requires additional clinic visits beyond Visit 801, or meets criteria for 
discharge from immunogenicity follow-up. A patient will stop immunogenicity follow-up visits 
when he or she either completes 3 additional quarterly visits (e.g., Week 100, Week 112, and 
Week 124) or completes a visit at which his or her ADA returns to baseline (2-fold titer from 
baseline), whichever occurs first.  Each subsequent visit after V801 will be scheduled only for 
those patients who meet the criteria for continued testing.  Once the patient meets the criteria for 
discharge from follow-up, either a telephone contact or clinic visit should be conducted to 
complete the patient’s participation in the study.  See the Schedule of Activities (Section 2) for 
the timing of events and the measures to be assessed.
Treatment-emergent ADAs are defined in Section 10.3.4.6.  A PK sample may be collected at 
the follow-up immunogenicity assessment(s) if warranted and agreed upon between both the 
investigator and sponsor.
In the event of drug hypersensitivity reactions (immediate or non-immediate), additional samples 
will be collected as close to the onset of the event as possible, but within 120 minutes, at the 

I5T-MC-AACG(d) Clinical Protocol
Page 72
LY3002813
resolution of the event, and 4-6 weeks following the event.  Instructions for the collection and 
handling of blood samples will be provided by the sponsor.  The actual date and time (24-hour 
clock time) of each sampling will be recorded. In the event of a finding of hypersensitivity, the 
investigator is to complete the CRF regarding the presence or absence of symptoms related to the 
hypersensitivity.
9.4.7.3.
Hepatic Safety Monitoring
If a study patient experiences elevated ALT ≥3X ULN, ALP ≥2X ULN, or elevated TBL ≥2X 
ULN, liver testing (Appendix 4) should be repeated within 3 to 5 days including ALT, AST, 
ALP, TBL, direct bilirubin, gamma-glutamyl transferase, and creatine kinase to confirm the 
abnormality and to determine if it is increasing or decreasing.  If the abnormality persists or 
worsens, clinical and laboratory monitoring should be initiated by the investigator and in 
consultation with the study medical monitor.  Monitoring of ALT, AST, TBL, and ALP should 
continue until levels normalize or return to approximate baseline levels.
Hepatic Safety Data Collection
Additional safety data should be collected via the CRF/electronic data entry if 1 or more of the 
following conditions occur:

elevation of serum ALT to ≥5X ULN on 2 or more consecutive blood tests

elevated serum TBL to ≥ 2X ULN (except for cases of known Gilbert’s 
syndrome)

elevation of serum ALP to ≥2X ULN on 2 or more consecutive blood tests

patient discontinued from treatment due to a hepatic event or abnormality of 
liver tests

hepatic event considered to be a SAE
9.4.7.4.
Amyloid-Related Imaging Abnormalities (ARIA-E and ARIA-H)
To ensure patient safety and to comply with regulatory guidance, the investigator is to consult 
with the Lilly-designated Medical Monitor regarding collection of specific recommended clinical 
information and follow-up MRIs.  In the event of a finding of ARIA-E on MRI, the investigator 
is to complete the CRF regarding the presence or absence of symptoms related to the ARIA-E.  
While most cases of ARIA-E are asymptomatic, when symptoms do occur, they are reported to 
be most commonly headache, worsening of cognitive function, alteration of consciousness, 
seizures, unsteadiness, and vomiting.  Even when symptomatic ARIA-E is present, in most cases, 
treatment is not required beyond a dose reduction (see Section 7.4.1) or temporary (see 
Section 8.1.1.1) or permanent (see Section 8.1) discontinuation of the LY3002813 treatment until 
the imaging abnormalities have resolved.  If a patient simultaneously develops more than one of 
the symptoms suggestive of ARIA-E, then an unscheduled MRI should be performed.  A single 
symptom suggestive of ARIA-E of sufficient severity may also warrant an MRI.

I5T-MC-AACG(d) Clinical Protocol
Page 73
LY3002813
If the above-mentioned symptoms are reported, and ARIA-E is suspected, then the abnormality 
is best detected by fluid attenuation inversion recovery (FLAIR) sequences on MRI and ARIA-H 
is best detected with the T2* gradient-recalled echo on MRI.
An unscheduled MRI with these imaging sequences should be obtained upon suspicion of ARIA.  
If ARIA is present, it is recommended to repeat MRIs with these sequences every 4 to 6 weeks 
until resolution of ARIA-E or stabilization of ARIA-H is documented.  For asymptomatic or 
mild symptoms, the patient can be observed; for moderate symptoms associated with ARIA-E, 
the use of oral or IV steroids can be considered.  In the case of severe symptoms associated with 
ARIA-E, it is recommended to hospitalize the patient for close observation and consider the use 
of IV steroids such as high-dose dexamethasone or a similar agent.
The unscheduled MRI should be performed in the same manner as the currently scheduled MRIs 
in the protocol, which includes sending the images for central review.
9.4.8. Appropriateness of Safety Assessments
The clinical safety measurements (AE reporting, physical examinations, neurological 
examinations, vital signs, ECGs, and clinical safety laboratory tests [including immunogenicity]; 
Section 9.2 and Section 9.4) are well-established methods in drug development research and are 
standard procedures for clinical trials.
Performance of MRIs is indicated based on the potential for the occurrence of ARIA during 
treatment with LY3002813.  Therefore, Study AACG will include serial MRIs beginning at 
baseline and following dosing according to the Schedule of Activities for assessment of ARIA.
LY3002813 is an antibody therapy.  As noted previously, a high prevalence of LY3002813 
ADAs was observed in Study AACC and AACD; therefore, immunogenicity analyses are 
indicated.  Blood samples for the assessment of immunogenicity will be taken at regular intervals 
throughout the dosing and follow-up periods.
Performance of ophthalmological and dermatological examinations is indicated in subjects who 
were previously treated with LY3202626, based on the potential for the occurrence of adverse 
retinal effects and hypopigmentation, respectively, during treatment with LY3202626.  While 
LY3202626 is no longer being administered in this study, dermatological and ophthalmological 
examinations in subjects who previously received this therapy or oral placebo will be performed 
at the next scheduled examination time point after their final dose of oral study medication, in 
accordance with the Schedule of Activities (Section 2).  Patients who received LY3202626/oral 
placebo after their Visit 8 or 9 dermatological or ophthalmological examination are to have an 
unscheduled examination at the next available opportunity.  Patients screened or randomized 
under the current amendment are not required to undergo any dermatological or 
ophthalmological examinations at baseline or any other study visits.
9.5.
Pharmacokinetics
At the visits and times specified in the Schedule of Activities (Section 2), venous blood samples 
of approximately 4 mL each will be collected to determine the serum concentrations of 

I5T-MC-AACG(d) Clinical Protocol
Page 74
LY3002813
LY3002813.  Instructions for the collection and handling of blood samples will be provided by 
the sponsor.  The actual date and time (24-hour clock time) of each sampling will be recorded.
Drug concentration information that may unblind the study will not be reported to investigative 
sites or blinded personnel until the study has been unblinded.
A maximum of 3 blood samples per patient may be drawn at additional time points during the 
study, if warranted and agreed upon between both the investigator and sponsor.  Instructions for 
the collection and handling of blood samples will be provided by the sponsor.
If LY3002813 infusion is permanently discontinued but the patient remains in the study, one PK 
sample should be collected at the soonest scheduled visit regardless if serum LY3002813 is on 
the Schedule of Activities at that visit. Dosing dates and times should be collected.  Subsequent 
PK sample collection should follow the protocol Schedule of Activities for serum LY3002813 
collection unless the scheduled visit exceeds 6 months since discontinuation of infusions. No 
additional serum collection for LY3002813 is required once the patient exceeds 6 months since 
discontinuation of LY3002813 infusions.
Bioanalytical samples collected to measure LY3002813 or LY3202626 concentrations will be 
retained for a maximum of 1 year following last subject visit for the study. During this time, 
samples remaining after the bioanalyses may be used for exploratory analyses such as 
metabolism, protein binding, or bioanalytical method development/validation work.
9.6.
Pharmacodynamics
9.6.1. Clearance of Amyloid Deposits
Florbetapir F18 PET provides quantitative assessment of amyloid plaque deposition in the brain 
and can serve as a PD biomarker of clearance of amyloid deposits.
Clearance of amyloid deposits (as assessed by florbetapir F18 PET signal) will be compared in 
LY3002813- and placebo-treated patients for those patients who undergo baseline, Visit 8 (Week 
24), Visit 15 (Week 52) and endpoint Visit 21(Week 76) or ED florbetapir F18 PET scans as 
described in the Schedule of Activities (Section 2).
9.6.2. Accumulation of Tau Deposits
Flortaucipir F18 PET provides quantitative assessment of tau PHF in the brain and can serve as a 
PD biomarker of accumulation of tau deposits as AD progresses.
Extent of accumulation of tau PHF deposits (as assessed by flortaucipir F18 PET signal) will be 
compared in LY3002813- and placebo-treated patients for those patients who undergo baseline 
and endpoint Visit 21 (Week 76) or ED) flortaucipir F18 PET scans as described in the Schedule 
of Activities (Section 2).

I5T-MC-AACG(d) Clinical Protocol
Page 75
LY3002813
9.7.
Pharmacogenomics [OR] Genetics
9.7.1. Apolipoprotein E Genotyping
Apolipoprotein E (APOE) genotyping is a mandatory part of this study, unless country-specific 
laws and regulations prohibit this type of testing.  Blood sampling for APOE genotyping will be 
performed as shown in the Schedule of Activities (Section 2).  Neither patients nor investigators 
will receive the genotype results unless there is a country-specific law or regulation that requires 
notification of the results.  Failure to collect samples for APOE will not be considered a protocol 
deviation if country-specific regulations prohibit the testing of genetic material or transportation 
of such material outside of the country.
9.7.2. Whole Blood Samples for Pharmacogenetic Research
A whole blood sample will be collected for pharmacogenetic analysis as specified in the 
Schedule of Activities (Section 2) where local regulations allow.
Samples will not be used to conduct unspecified disease or population genetic research either 
now or in the future.  Samples will be used to investigate variable response to LY3002813 and to 
investigate genetic variants thought to play a role in AD.  Assessment of variable response may 
include evaluation of AEs or differences in efficacy.
All samples will be coded with the patient number.  These samples and any data generated can 
be linked back to the patient only by the investigator site personnel.
Samples will be retained at a facility selected by Lilly or its designee for a maximum of 15 years 
after the last patient visit for the study, or for a shorter period if local regulations and/or 
ERBs/investigational review boards (IRBs) impose shorter time limits.  This retention period 
enables use of new technologies, response to regulatory questions, and investigation of variable 
response that may not be observed until later in the development of LY3002813 and LY3202626 
or after LY3002813 and LY3202626 become commercially available.
Molecular technologies are expected to improve during the 15-year storage period and therefore 
cannot be specifically named.  However, existing approaches include whole genome or exome 
sequencing, genome wide association studies, and candidate gene studies.  Regardless of 
technology utilized, genotyping data generated will be used only for the specific research scope 
described in this section.
9.8.
Biomarkers
Biomarker research is performed to address questions of relevance to drug disposition, target 
engagement, PD, mechanism of action, variability of patient response (including safety), and 
clinical outcome.  Sample collection is incorporated into clinical studies to enable examination of 
these questions through measurement of biomolecules including deoxyribonucleic acid (DNA), 
ribonucleic acid (RNA), proteins, lipids, and other cellular elements.
Serum, plasma, and whole blood RNA samples for biomarker research will be collected at the 
times specified in the Schedule of Activities (Section 2) where local regulations allow.

I5T-MC-AACG(d) Clinical Protocol
Page 76
LY3002813
Samples will be used for research on the drug target, disease process, variable response to 
LY3002813 and/or LY3202626, pathways associated with AD, mechanism of action of 
LY3002813 and LY3202626, and/or research method or in validating diagnostic tools or assay(s) 
related to AD.
All samples will be coded with the patient number.  These samples and any data generated can 
be linked back to the patient only by the investigator site personnel.
Samples will be retained at a facility selected by Lilly or its designee for a maximum 15 years 
after the last patient visit for the study, or for a shorter period if local regulations and ERBs 
impose shorter time limits.  This retention period enables use of new technologies, response to 
regulatory questions, and investigation of variable response that may not be observed until later 
in the development of LY3002813 and LY3202626 or after LY3002813 and LY3202626 become 
commercially available.
9.9.
Medical Resource Utilization and Health Economics
Dependence, or the level of assistance required by a patient, has been suggested as a construct 
for assessing the effect of AD treatment.  The process of increasing dependence on others is 
intended as a complementary measure to existing clinical measures in order to help explain the 
impact of AD on economic issues such as the risk of institutionalization and caregiver burden 
(McLaughlin et al. 2010; Spackman et al. 2013).  Recently, the Alzheimer’s Disease Cooperative 
Study Activities of Daily Living Inventory (ADCS-ADL) scores were used to map individuals 
into one of six dependence levels (0 to 5):  Level 0 – No iADL/bADL impairment; Level 1 –
Some supervision needed on isolated iADLs; Level 2 – Supervision on multiple iADLs or loss of 
at least 1 household activity; Level 3 – Supervision on all types of iADLs or homebound; Level 
4 – Supervision on some bADLs; and Level 5 – Impaired transfer or complete incontinence 
(Kahle-Wrobleski et al. 2015). An approach to transforming continuous functional scale scores 
into discrete levels of dependence was examined previously in a longitudinal observational 
study, with preliminary results suggesting acceptable validity and progression in dependence 
level over time (Kahle-Wrobleski et al. 2017). At baseline, 49.6% of those with mild AD 
dementia were dependence level 2 and 42.7% were at levels 3 or 4. At 18 months, the 
proportion of patients at level 2 declined to 31.2% while that at levels 3 and 4 rose to 
58.8%. Analyses will be conducted to examine changes in dependence levels across the trial 
population as well as potential differences on dependence level by treatment group assignment.

I5T-MC-AACG(d) Clinical Protocol
Page 77
LY3002813
10. Statistical Considerations
10.1. Sample Size Determination
Approximately 250 subjects will be enrolled and randomized in a 1:1 ratio to the 2 treatment 
arms (placebo and LY3002813).  It is expected that approximately 200 subjects will complete 
the double-blind treatment period of the study (approximately 100 per treatment arm). This 
sample size will provide approximately 84% power to demonstrate that the active treatment arm 
has a ≥ 0.6 posterior probability of slowing down iADRS progression over placebo by at least 
3 points.  The assumption for power calculation is that mean progression levels in the placebo 
and LY3002813 arms are approximately 12 and 6 points (50% slowing) over 18 months, 
respectively, with common standard deviation of 17.  If the active treatment arm is placebo-like 
with no efficacy, the probability of passing the efficacy criterion specified above (i.e., false 
positive) is approximately 6%.  The simulation for the power calculation and sample size 
determination was carried out in FACTS Version 6.0.
10.2. Populations for Analyses
For purposes of analysis, in general the following populations are defined unless otherwise 
specified:
For efficacy analysis, the Full Analysis Set will group patients according to randomized 
treatment assignment (LY3002813 or placebo), even if the patient does not take the assigned 
treatment, does not receive the correct treatment, or otherwise does not follow the protocol.  
When change from baseline is assessed, patients will be included in the analysis only if both a 
baseline and at least 1 valid post-baseline measure are available.
For safety analysis, all patients who received at least 1 dose of randomized study treatment 
(LY3002813 or placebo) will be included in the safety analysis set.  In safety data presentations, 
erroneously treated patients (e.g., those randomized to “Treatment A” but actually given 
“Treatment B”) will be accounted for in their actual treatment groups.
There were approximately 48 patients randomized before the removal of LY3202626 treatment 
in protocol amendment (d) (about 16 each in the LY3002813 and LY3202626 combination 
therapy arm, LY3002813 monotherapy arm, and placebo arm). Patients already randomized to 
the former LY3002813 monotherapy arm and placebo arm will be pooled with patients 
randomized after protocol amendment (d) to form the Full Analysis Set and safety analysis set 
specified above. Data from patients randomized to the LY3002813 and LY3202626 
combination therapy arm will be summarized separately and will not be included in treatment 
comparisons on efficacy and safety endpoints. The total number of patients to be randomized in 
the study is approximately 266. 

I5T-MC-AACG(d) Clinical Protocol
Page 78
LY3002813
10.3. Statistical Analyses
10.3.1. General Statistical Considerations
Unless otherwise noted, all pairwise tests of treatment effects will be conducted at a 2-sided 
alpha level of 0.05; 2-sided CIs will be displayed with a 95% confidence level. All tests of 
interactions between treatment and other factors will be conducted at an alpha level of 0.05.  
Bretz’ graphical approach may be utilized to provide strong control of the study wise Type I 
error rate for the primary and key secondary hypotheses at alpha level of 0.05 (Bretz et al. 2009; 
Bretz et al. 2011).  Details on the graphical approach and testing strategy will be specified in the 
statistical analysis plan (SAP).
All efficacy analyses will follow the intent-to-treat (ITT) principle unless otherwise specified. 
An ITT analysis is an analysis of data by the groups to which subjects are assigned by random 
allocation, even if the subject does not take the assigned treatment, does not receive the correct 
treatment, or otherwise does not follow the protocol.
When change from baseline is assessed, subjects will be included in the analysis only if both a 
baseline and a postbaseline measure are available.  Unless otherwise defined, a baseline measure 
is the last nonmissing observation collected prior to the first administration of study medications.  
Endpoint is the last nonmissing postbaseline measurement.
For MMRM models, observations collected at nonscheduled visits will not be included in the 
analyses.
A database lock is expected to occur after all randomized subjects have had chance to complete 
double-blind period of the study. Efficacy and safety analyses will be conducted based on data 
collected during double-blind period. Data collected during immunogenicity and safety follow-
up period will be summarized and analyzed separately.
Any change to the data analysis methods described in the protocol will require an amendment 
ONLY if it changes a principal feature of the protocol.  Any other change to the data analysis 
methods described in the protocol and the justification for making the change will be described 
in the SAP and clinical study report.  Additional exploratory analyses of the data will be 
conducted as deemed appropriate.
Details of the statistical methods are specified in the SAP for Study AACG.
10.3.1.1. Handling of Missing Items for Scales
If any of the individual items for ADAS-Cog or ADCS-ADL are missing or unknown, every 
effort will be made to obtain the score for the missing item or items.
For ADAS-Cog13, if 4 or fewer of a total of 13 items are missing, the total score (maximum =85)
will be imputed as follows:  The total from remaining items will be multiplied by a factor that 
includes the maximum score for the missing items.  For example, if the first item, “Word-Recall
Task,” which ranges from a score of 0 through 10 (maximum = 10), is missing, and the second 
item “Commands,” which ranges from a score of 0 to 5 (maximum = 5), is missing, then the 

I5T-MC-AACG(d) Clinical Protocol
Page 79
LY3002813
multiplication factor = 85/(85 - [10 + 5]) = 85/70 = 1.21.  Thus, the total score for this example 
will be the sum of the remaining 12 items multiplied by 1.21.  The imputed number will be 
rounded up to the nearest integer.  If more than 4 items are missing, the total score for 
ADAS-Cog13 at that visit will be considered missing.
For the ADCS-iADL, if <30% of the items are missing, the total score will be imputed.  The sum 
of the nonmissing items will be prorated to the sum of total items.  The imputed number will be 
rounded up to the nearest integer.  If the nearest integer is greater than the maximum possible 
score, the imputed score will be equal to the maximum score.  If >30% of the items are missing, 
the total score for ADCS-iADL at that visit will be considered missing.  The same imputation 
technique will be applied to the ADCS-ADL total score.  Note that, depending on the specific 
item responses that are missing, it is possible to have an imputed total score for both the ADCS-
iADL and the ADCS-ADL, an imputed total score for one but not the other, or both total scores 
missing.
The same imputation technique will be applied to the CDR-SB.  If only 1 box (of 6) of the CDR 
is missing, the sum of the boxes will be imputed by prorating the sum from the other 5 boxes.  If 
the score from more than 1 box is not available, the CDR-SB at that visit will be considered 
missing.
iADRS score is calculated as – ADAS-Cog13 score + 85 + ADCS-iADL score.  If either 
ADAS-Cog13 or ADCS-iADL is missing, iADRS score will be considered missing.
For all other scales, if any item is missing, any total or sum involving that item will be 
considered missing.
10.3.2. Treatment Group Comparability
10.3.2.1. Subject Disposition
All patients who discontinue from the study will be identified, and the extent of their 
participation in the study will be reported.  If known, a reason for their discontinuation will be 
given.
The reasons for discontinuation will be collected when the patient’s participation in the study 
ends and will be summarized by treatment group for all randomized subjects.  The percentage of 
subjects discontinuing from each treatment group will be compared between groups using 
Fisher’s exact test.  The comparisons will be done for the overall percentage of patients who 
discontinue and for select specific reasons for discontinuation.
10.3.2.2. Subject Characteristics
The patient’s age, gender, race, height, body weight, BMI (weight (kg) / [height (m)]2), tobacco 
use, alcohol use, caffeine use, years of education, work status, time since onset of first AD 
symptoms, time since diagnosis, baseline MMSE, CBB score at Visit 1, apolipoprotein E 
(APOE) genotype (E4 carrier vs. non-carrier), having 1 or more first degree relatives with AD, 
and AChEI and/or memantine use at baseline will be recorded.

I5T-MC-AACG(d) Clinical Protocol
Page 80
LY3002813
Baseline characteristics will be summarized by treatment group and overall.  Summaries will 
include descriptive statistics for continuous and categorical measures.  Fisher’s exact test or 
Pearson’s chi-square test will be used for treatment-group comparisons of categorical data.  For 
continuous data, analysis of variance (ANOVA), with independent factors for treatment and 
investigator, will be used.
10.3.2.3. Prior and Concomitant Therapy
Prior medications are defined as those that stop before randomization (Visit 2).  Concomitant 
medications are defined as those being taken on or after randomization (Visit 2).  A summary of 
concomitant medications will be presented as frequencies and percentages for each treatment 
group.  Fisher’s exact test will be used to test for treatment differences between groups.
If the start or stop dates of therapies are missing or partial to the degree that determination cannot 
be made of whether the therapy is prior or concomitant, the therapy will be deemed concomitant.
Prior and concomitant medications will be listed.
Summary tables will also be provided for concomitant anticholinergics that affect cognitive 
function and AChEI/memantine medications.
Medications will be coded using the World Health Organization (WHO) drug dictionary.
10.3.2.4. Treatment Compliance
Summary statistics for LY3002813 treatment compliance will be provided for the total number 
of complete infusions received, duration of complete infusion, and volume of complete infusion 
by treatment group.
Frequencies and percentages of reasons why infusion was stopped will also be presented.
Summary statistics for LY3202626 treatment compliance will be provided for the proportion of 
patients who are compliant and noncompliant as noted in Section 7.6 of this protocol by 
treatment group.
10.3.3. Efficacy Analyses
10.3.3.1. Primary Analyses
The primary objective of this study is to test the hypothesis that IV infusion of LY3002813 will 
slow the cognitive and/or functional decline of AD as measured by the composite measure 
iADRS compared with placebo in patients with early symptomatic AD.  This will be assessed 
using an MMRM analysis.
The change from baseline score on the iADRS at each scheduled postbaseline visit (according to 
the Schedule of Activities) during the treatment period will be the dependent variable.  The 
model for the fixed effects will include the following terms:  baseline score, pooled investigator, 
treatment, visit, treatment-by-visit interaction, baseline-by-visit interaction, concomitant AChEI 
and/or memantine use at baseline (yes/no), and age at baseline.  Visit will be considered a 
categorical variable.  The null hypothesis is that the contrast between the LY3002813 group 
versus placebo at the last visit equals zero.  An unstructured covariance matrix will be used to 

I5T-MC-AACG(d) Clinical Protocol
Page 81
LY3002813
model the within-subject variance-covariance errors.  If the unstructured covariance structure 
matrix results in a lack of convergence, the following tests will be used in sequence:  
heterogeneous Toeplitz covariance structure, heterogeneous autoregressive covariance structure, 
heterogeneous compound symmetry covariance structure, and compound symmetry covariance 
structure.  The Kenward-Roger approximation will be used to estimate the denominator degrees 
of freedom.
The primary time point for treatment comparison will be at Week 76.  The treatment group 
contrast in least-squares mean progression and its associated p-value and 95% CI will be 
calculated for the treatment comparison of LY3002813 vs. placebo using the MMRM model 
specified above.  In addition, Bayesian posterior probability of the active treatment arm being 
superior to placebo by at least a margin of interest (25% slowing of placebo progression) will 
also be calculated assuming a non-informative prior.
10.3.3.2. Secondary Efficacy Analyses
Similar to the primary analysis, each of the secondary efficacy outcomes will be assessed using 
an MMRM analysis.  These secondary efficacy outcomes include ADAS-Cog13, ADCS-iADL,
CDR-SB, and MMSE.  For each secondary efficacy measure, the change from baseline score at 
each scheduled postbaseline visit (according to the Schedule of Activities) during the treatment 
period will be analyzed using the same MMRM model described for the primary analysis.
Longitudinal changes from baseline in amyloid plaque (as measured by florbetapir F18 PET 
scan) and vMRI parameters will be analyzed using MMRM including the following terms in the 
model:  baseline biomarker value, treatment, visit, treatment-by-visit interaction, and baseline-
by-visit interaction.  The change from baseline to endpoint in tau SUVr (as measured by 
flortaucipir PET scan) will be analyzed using an analysis of covariance (ANCOVA) model with 
terms of baseline value and treatment.
Any additional analyses of secondary efficacy outcomes and biomarkers will be specified in the 
SAP.
10.3.4. Safety Analyses
All subjects who receive at least 1 dose of LY3002813 will be evaluated for safety and 
tolerability.  Safety parameters (AEs, laboratory analytes, vital signs, ECGs, and MRIs) will be 
summarized using descriptive statistics for continuous variables and frequencies along with 
percentages for categorical variables during the treatment period.
10.3.4.1. Adverse Events
Treatment-emergent adverse events will be defined as events that first occurred or worsened on 
or after randomization (Visit 2).  Should there be insufficient data for AE start date and stop date 
the AE will be considered treatment emergent.
Treatment-emergent adverse events will be calculated based on adverse event identifier (AEID) 
and coded according to established Medical Dictionary for Regulatory Activities (MedDRA) 
terms and summarized by MedDRA System Organ Class (SOC) and Preferred Term.

I5T-MC-AACG(d) Clinical Protocol
Page 82
LY3002813
An overview of AEs, including the number and percentage of subjects who died, had SAEs, 
discontinued due to AEs, and who had treatment-emergent AEs (TEAEs), will be summarized by 
treatment group.
10.3.4.2. Vital Signs and Weight
Vital sign measurements and weight will be analyzed using continuous data (change from 
baseline) and categorical data (proportion of treatment-emergent abnormalities).
Summary statistics will be presented for observed values at baseline and for change from 
baseline results at each scheduled postbaseline visit and at endpoint(s).  Systolic and diastolic 
blood pressure and pulse (collected in sitting position), temperature, and weight will be 
summarized.
The incidence of treatment-emergent abnormal high or low vital signs and weight will be 
summarized by treatment groups.  Treatment-emergent vital sign evaluations are defined for 
evaluations collected after the initiation of study medication.  Abnormal criteria for vital signs 
and weight are presented in Table AACG.10.1.  Any vital sign or weight outside the criterion 
values will be considered abnormal.
Table AACG.10.1.
Criteria for Abnormal Vital Signs
Vital Sign Parameter (Unit)
Postbaseline Low Criteria
Postbaseline High Criteria
Sitting Systolic Blood Pressure 
(mmHg)
Absolute value 90 and 20 decrease 
from baseline
Absolute value 160 and 20 increase 
from baseline
Sitting Diastolic Blood Pressure 
(mmHg)
Absolute value 50 and 10 decrease 
from baseline
Absolute value 100 and 10 increase 
from baseline
Sitting Pulse (bpm)
Absolute value <50 and 15 decrease 
from baseline
Absolute value >100 and 15 increase 
from baseline
Weight
4% decrease
4% increase
Vital Sign Parameter (Unit)
Postbaseline Criteria for Abnormality
Orthostatic Systolic Blood 
Pressure (mmHg)
20 mmHg decrease in systolic blood pressure (supine to standing) 
(i.e., supine minus standing 20)
Orthostatic Diastolic Blood 
Pressure (mmHg)
≥10 mmHg decrease in diastolic blood pressure (supine to standing)
(i.e., supine minus standing ≥10 mm Hg)
Orthostatic Pulse (bpm)
30 increase in bpm (standing to supine) (i.e., standing minus supine 30)
Temperature
Absolute value 38.3C and 1.1C increase from baseline
(Absolute value 101F and 2F increase from baseline)
Abbreviation:  bpm = beats per minute.
10.3.4.3. Laboratory Analyses
Laboratory measurements will be analyzed as continuous data (change from baseline) measured 
as International System Units (SI) or as categorical data (proportion of treatment-emergent 
abnormalities).

I5T-MC-AACG(d) Clinical Protocol
Page 83
LY3002813
If there are multiple records of laboratory measurements at baseline or postbaseline visits, the 
last record will be used.
Change from baseline to postbaseline visits at which laboratory measurements are taken will be 
summarized using descriptive statistics.
For all laboratory analytes, frequencies of subjects with notable changes (i.e., increases or 
decreases of a prespecified amount unique to each analyte) from baseline to each postbaseline 
visit will also be summarized for all subjects and stratified by low, normal, or high at baseline.
10.3.4.4. Electrocardiograms
The ECG measurements will be analyzed using continuous data (change from baseline) and 
categorical data (proportion of treatment-emergent abnormalities).
Since ECG is measured in triplicates during the double-blind period, the average of triplicates 
will be used at baseline and each double-blind period visit.  If there are multiple records after 
averaging ECG triplicates within a visit, the last record of averages will be used.
The analysis will be done for the following ECG measurements:  heart rate, PR, QT, QTc, and 
RR intervals and QRS duration.  All analyses of QTc will be carried out using the Fridericia 
correction (QTcF) method.  These summaries will include data from each visit ECG measures 
are performed.
Change from baseline to each postbaseline visit at which ECG measurements are taken will be 
assessed using an MMRM model.  The model for the fixed effects will include terms for the 
following independent effects:  baseline ECG score, pooled investigator, treatment, visit, 
treatment-by-visit interaction, baseline-by-visit interaction and age at baseline.  This analysis 
will be done separately for each ECG parameter.
Incidence of treatment-emergent abnormal ECGs will be assessed by comparisons at (1) anytime 
and (2) each postbaseline visit between treatment groups with Fisher’s exact test.  For analyses 
of treatment-emergent abnormal ECGs, baseline will be considered as all visits before the 
initiation of drug dose.
Abnormal ECG criteria are presented in Table AACG.10.2 and criteria for abnormal QTcF 
prolongation are presented in Table AACG.10.3.

I5T-MC-AACG(d) Clinical Protocol
Page 84
LY3002813
Table AACG.10.2.
Criteria for Abnormal ECG Parameters
ECG Parameter
Low Criteria
High Criteria
Heart Rate
<50 bpm
>100 bpm
PR Interval
<120 msec
220 msec
QRS Duration 
<60 msec
120 msec
QTc Interval
            males
            females
       males and females
<330 msec
<340 msec
450 msec
470 msec
> 500 msec
Abbreviations:  bpm = beats per minute; ECG = electrocardiogram; QTc = corrected QT.
Table AACG.10.3.
Criteria for Prolonged ECG QTcF Interval
QTc Delta Changes (msec)
>30
>60
>75
Abbreviations:  QTc = corrected QT; QTcF = Fridericia-corrected QT.
Treatment-emergent high ECG parameters (heart rate, PR interval, QRS duration, and QT and 
QTcF intervals) are the values that are low or normal at all baseline visits and fall into the high 
abnormal categories in Table AACG.10.2 and Table AACG.10.3 postbaseline.  Similarly, 
treatment-emergent low ECG parameters (heart rate, PR interval, and QRS duration) are the 
values that are high or normal at all baseline visits and fall into the low abnormal categories 
above.
For each treatment-emergent high ECG parameter in Table AACG.10.2, only subjects who were 
low or normal at baseline and have at least 1 postbaseline value will be included in the 
denominator when computing the proportion of subjects with treatment-emergent high values.  
Similarly, only subjects who were high or normal at baseline and have at least 1 postbaseline 
value will be included in the denominator when computing the proportion of subjects with 
treatment-emergent low values.
For prolonged QTcF interval assessments, when computing the proportion of subjects with 
treatment-emergent high abnormalities, only subjects who were normal at baseline and had a 
nonmissing result at that postbaseline visit will be included in the denominator.  A 
treatment-emergent high value is defined as a change from normal value at all baseline 
assessments to a value greater than 450 msec for males and 470 msec for females at postbaseline.
In addition, treatment differences in the proportion of subjects who have normal baselines with a 
change to abnormal high or abnormal low values at any postbaseline visits will be summarized.  
Treatment-emergent qualitative ECG findings will also be summarized.

I5T-MC-AACG(d) Clinical Protocol
Page 85
LY3002813
10.3.4.5. ARIA-E and ARIA-H
The incidence of ARIA-E will be summarized.  Change in ARIA-E status from baseline, to each 
subsequent MRI (in the event of unscheduled MRIs), and to double-blind period endpoint 
(Visit 21) will be compared between treatment groups using Fisher’s exact test.
The incidence of changes in ARIA-H will be summarized.  Change in ARIA-H status from 
baseline to endpoint will be compared between treatment groups using Fisher’s exact test.  The 
number and percentage of subjects with increases in size of preexisting ARIA-H, number of 
subjects with increases in number of ARIA-H, and number of subjects with increases in size of 
preexisting and/or number of ARIA-H from baseline to endpoint will be summarized for both 
treatment groups and compared using Fisher’s exact test.
Subjects with ARIA-E and subjects with ARIA-H that increased in size and/or number 
postbaseline, and subjects with any other MRI findings will be listed.
10.3.4.6. Evaluation of Immunogenicity
Subject samples will be analyzed using a 4-tiered approach.  All samples will be assessed in Tier 
1 (screening) for the possible presence of ADA.  Samples found to produce a signal above or 
equal to the screening cut point will be assessed in Tier 2 to confirm specificity to LY3002813 
(confirmation).  Any samples confirmed as specific for anti-LY3002813 antibodies will be 
reported as “detected.”  All samples below the screening cut point (Tier 1) or not confirmed (Tier 
2) will be reported as “not detected.”  Any “detected” sample in Tier 2 will be assessed in Tier 3 
(titer assessment) and Tier 4 (neutralizing antibodies).  Anti-drug antibodies titer values will be 
reported from Tier 3 titer assessment.  Any samples above the Tier 4 assay cut point will be 
reported as “detected for neutralizing antibodies”; samples below the assay cut point in Tier 4 
will be reported as “not detected for neutralizing antibodies.”
The frequency and percentage of subjects with preexisting (baseline) ADA, ADA at any time 
after baseline, and TE ADA to LY3002813 will be tabulated.  If no ADAs are detected at 
baseline, TE ADA are defined as those with a titer 2 fold (1 dilution) greater than the MRD of 
the assay.  For samples with ADA detected at baseline TE ADA are defined as those with a 4-
fold (2 dilutions) increase in titer compared to baseline.  For the TE ADA subjects, the 
distribution of maximum titers will be described.  The frequency of neutralizing antibodies may 
also be tabulated.  The relationship between the presence of antibodies to LY3002813 and PK, 
PD, safety and/or efficacy assessment may be assessed.
10.3.4.7. Suicidal Ideation and Behavior
Suicide-related thoughts and behaviors, based on the C-SSRS, will be listed by subject and visit.  
Only subjects that show suicidal ideation/behavior will be displayed (i.e., if a subject’s answers 
are all “no” for the C-SSRS, then that subject will not be displayed).  However, if a subject 
reported any ideation or behavior at any time point, then all their ideation and behavior will be 
displayed, even if not positive.

I5T-MC-AACG(d) Clinical Protocol
Page 86
LY3002813
10.3.5. Pharmacokinetic/Pharmacodynamic Analyses
Compartmental modeling of LY3002813 PK data using nonlinear mixed effects modeling or 
other appropriate software may be explored, and population estimates for clearance and central
volume of distribution may be reported.  Depending on the model selected, other PK parameters 
may also be reported.  Exploratory graphical analyses of the effect of dose level or demographic 
factors on PK parameters may be conducted.  If appropriate, data from other studies of 
LY3002813 may be used in this analysis.
Concentrations of LY3202626 were collected under the original version of this protocol, as well 
as amendments (a-c). These data will be summarized in the final study report and may be 
analyzed graphically. If appropriate, exploratory analyses may be conducted to evaluate 
potential relationships between LY3202626 concentrations and LY3002813 concentration.
The PK/PD relationships between plasma LY3002813 concentration and SUVr, cognitive 
endpoints, ARIA incidence rate or other markers of PD activity may be explored graphically.  
The relationship between the presence of antibodies to LY3002813 and PK, PD, safety and/or 
efficacy may be assessed graphically.
Additional modeling may be performed based on the results of the graphical analyses.
10.3.6. Interim Analyses
A limited number of pre-identified individuals may gain access to the limited unblinded data, as 
specified in the unblinding plan, prior to the interim or final database lock, in order to initiate the 
final population PK/PD model development processes for interim or final analyses.  Information 
that may unblind the study during the analyses will not be reported to study sites or blinded study 
team until the study has been unblinded.  It is intended that access prior to the final database lock 
will be granted after the last patient completes Visit 18 (after 64 weeks of treatment).
An independent external Data Monitoring Committee (DMC) is to monitor data on an ongoing 
basis to ensure the continuing safety of patients enrolled in this study. There will be periodic
safety data reviews during the study and the external DMC is authorized to evaluate results from 
unblinded safety data reviews. The timing and operational details of the DMC safety data 
reviews are defined in DMC charter.
At least one interim analysis may be conducted for Study AACG; for example, when all 
randomized subjects have had a chance to complete 52 weeks of treatment (Visit 15) and data 
will be used to evaluate whether to stop the study for futility.  Additional assessment of efficacy
may also be evaluated at the interim analyses to inform future development of the compounds
and platform. For such futility and efficacy analyses, an internal assessment committee (IAC), 
but external to the study team, is authorized to evaluate results from the unblinded interim 
analyses. Operational details and a quantitative framework to provide information for these 
decisions will be documented in the statistical analysis plan (SAP). Study sites will receive 
information about interim results ONLY if they need to know for the safety of their patients.
Unblinding details are specified in the unblinding plan section of the SAP or a separate 
unblinding plan document.

I5T-MC-AACG(d) Clinical Protocol
Page 87
LY3002813
11. References
Alaka K, Campbell G, Fleisher A, Hake A, Irizarry M, Miller B, Pontecorvo M, Siemers E, Sims 
J, Yaari R. The nosology of Alzheimer’s disease and application of concepts to amyloid-
targeting treatments: an internal summary of Lilly thinking. White Paper. 2015.
Alzheimer’s Association 2017a. Available at: http://alz.org/aaic/_downloads/draft-nia-aa-7-18-
17.pdf. Accessed August 24, 2017.
Alzheimer’s Association 2017b. Available at: http://alz.org/aaic/nia-aa.asp. Accessed August 24, 
2017.
Berg L, Miller JP, Baty J, Rubin EH, Morris JC, Figiel G. Mild senile dementia of the 
Alzheimer’s type. 4. Evaluation of intervention. Ann Neurol. 1992;31(3):242-249.
Black RS, Sperling RA, Safirstein B, Motter RN, Pallay A, Nichols A, Grundman M. A single 
ascending dose study of bapineuzumab in patients with Alzheimer disease. Alzheimer Dis 
Assoc Disord. 2010;24(2):198-203.
Braak H, Braak E. Evolution of the neuropathology of Alzheimer's disease. Acta Neurol Scand
Suppl. 1996;165:3-12.
Bretz F, Maurer W, Brannath W, Posch M. A graphical approach to sequentially rejective 
multiple test procedures. Stat Med. 2009;28:586-604.
Bretz F, Posch M, Glimm E, Klinglmueller F, Maurer W, Rohmeyer K. Graphical approaches for 
multiple comparison procedures using weighted Bonferroni, Simes, or parametric tests. Biom 
J. 2011;53(6):894-913.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 
1976;16(1):31-41.
Darby, D, Maruff, P, Collie, A, McStephen, M. Mild cognitive impairment can be detected by 
multiple assessments in a single day. Neurology. 2002;59(7):1042–1046.
Darby DG, Pietrzak RH, Fredrickson J, Woodward M, Moore L, Fredrickson A, Sach J, Maruff 
P. Intraindividual cognitive decline using a brief computerized cognitive screening test. 
Alzheimer’s Dement. 2012;8:95-104.
Davison, SL, Bell, RJ, Gavrilescu, M, Searle, K, Maruff, P, Gogos, A, Rossell SL, Adams J, 
Egan GF, Davis, SR. Testosterone improves verbal learning and memory in postmenopausal 
women: results from a pilot study. Maturitas. 2011;70(3):307-311.
DeMattos RB, Lu J, Tang Y, Racke MM, Delong CA, Tzaferis JA, Hole JT, Forster BM, 
McDonnell PC, Liu F, Kinley RD, Jordan WH, Hutton ML. A plaque-specific antibody clears 
existing β-amyloid plaques in Alzheimer's disease mice. Neuron. 2012;76(5):908-920.
Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Joffe S, Kieburtz K, Raman R, Sun X, 
Aisen P, for the Alzheimer's Disease Cooperative Study Steering Committee; Siemers E, Liu-
Seifert, Mohs R, for the Solanezumab Study Group. Phase 3 trials of solanezumab for mild-to-
moderate Alzheimer's disease. N Engl J Med. 2014;370:311-321.
Doraiswamy PM, Sperling RA, Coleman RE, Johnson KA, Reiman EM, Davis MD, Grundman 
M, Sabbagh MN, Sadowsky CH, Fleisher AS, Carpenter A, Clark CM, Joshi AD, Mintun MA, 

I5T-MC-AACG(d) Clinical Protocol
Page 88
LY3002813
Skovronsky DM, Pontecorvo MJ, AV45-A11 Study Group. Amyloid-β assessed by florbetapir 
F 18 PET and 18-month cognitive decline: a multicenter study. Neurology. 2012;79(6):1636-
1644.
[FDA] United States Food and Drug Administration. Guidance for Industry. Suicide ideation and 
behavior: prospective assessment of occurrence in clinical trials [draft guidance]. Available at: 
http://www.fda.gov/downloads/Drugs/Guidances/UCM225130.pdf. Accessed August 06, 
2017.
Fleisher AS, Chen K, Quiroz YT, Jakimovich LJ, Gutierrez Gomez M, Langois CM, Langbaum 
JBS Roontiva A, Thiyyagura P, Lee W, Ayutyanont N, Lopez L, Moreno S, Muñoz C, Tirado 
V, Acosta-Baena N, Fagan AM, Giraldo M, Garcia G, Huentelman MJ, Tariot PN, Lopera F, 
MD, Reiman EM. Associations between biomarkers and age in the presenilin 1 E280A 
autosomal dominant Alzheimer disease kindred: a cross-sectional study. JAMA Neurol. 
2015;72:316-24.
Fleisher AS, Lowe SL, Liu P, Shcherbinin S, Li L, Chua L, Nakano M, Hawdon A, Willis BA, 
Schwarz AJ, DeMattos RB, Mintun MA, Irizarry MC. Significant and sustained florbetapir 
F18 uptake reduction in patients with symptomatic Alzheimer’s disease with LY3002813, a 
β-amyloid plaque-specific antibody. Presented at the Alzheimer’s Association International 
Conference 2018, July 22, 2018, Chicago, IL.
Fredrickson J, Maruff P, Woodward M, Moore L, Fredrickson A, Sach J, Darby D. Evaluation of 
the usability of a brief computerized cognitive screening test in older people for 
epidemiological studies. Neuroepidemiol. 2010;34:65-75.
Freemantle N, Calvert M, Wood J, Eastaugh J, Griffin C. Composite outcomes in randomized 
trials. Greater precision but with greater uncertainty? JAMA. 2003;289(19):2554-2559.
18F florbetapir Injection (AmyvidTM) Package Insert. Indianapolis, IN: Eli Lilly and Company; 
2013.
Folstein MF, Folstein SE, McHugh PR. “Mini-Mental State”. A practical method for grading the 
cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(13):189-198.
Galasko D, Bennett D, Sano M, Ernesto C, Thomas R, Grundman M, Ferris S. An inventory to 
assess activities of daily living for clinical trials in Alzheimer’s disease. The Alzheimer’s 
Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997;11(Suppl 2):S33-S39.
Galasko D, Kershaw PR, Schneider L, Zhu Y, Tariot PN. Galantamine maintains ability to 
perform activities of daily living in patients with Alzheimer’s disease. J Am Geriat Soc. 
2004;52(7):1070-1076.
Hachinski VC, Iliff LD, Zilhka E, Du Boulay GH, McAllister VL, Marshall J, Russell RW, 
Symon L. Cerebral blood flow in dementia. Arch Neurol. 1975;32(9):632-637.
Jaeger, J, Hårdemark, H-G, Zettergren, A, Sjögren, N, Hannesdottir, K. Does repeated daily 
testing improve measurement sensitivity to the cognitive effects of donepezil in mild-to-
moderate Alzheimer’s Disease? Alzheimers Dement. 2011:7(4):e59. (Paper presented at the 
Alzheimer’s Association International Conference, Paris, France).
Jonsson T1, Atwal JK, Steinberg S, Snaedal J, Jonsson PV, Bjornsson S, Stefansson H, Sulem P, 
Gudbjartsson D, Maloney J, Hoyte K, Gustafson A, Liu Y, Lu Y, Bhangale T, Graham RR, 

I5T-MC-AACG(d) Clinical Protocol
Page 89
LY3002813
Huttenlocher J, Bjornsdottir G, Andreassen OA, Jönsson EG, Palotie A, Behrens TW, 
Magnusson OT, Kong A, Thorsteinsdottir U, Watts RJ, Stefansson K. A mutation in APP 
protects against Alzheimer's disease and age-related cognitive decline. Nature. 
2012;488(7409):96-99.
Kahle-Wrobleski K, Andrews JS, Belger M, Gauthier S, Stern Y, Rentz DM and Galasko D. 
Clinical and economic characteristics of milestones along the continuum of Alzheimer’s 
disease: transforming functional scores into levels of dependence. J Prevention of Alzheimer’s 
Dis. 2015;2(2):115-120.
Kahle-Wrobleski K, Andrews JS, Belger M, Ye W, Gauthier S, Rentz DM and Galasko D. 
Dependence levels as interim clinical milestones along the continuum of Alzheimer’s disease: 
18-month results from the GERAS Observational Study. J Prev Alzheimers Dis. 2017;4(2):72-
80.
Ketter N, Brashear HR, Bogert J, Di J, Miaux Y, Gass A, Purcell DD, Barkhof F, Arrighi HM. 
Central review of amyloid-related imaging abnormalities in two phase III clinical trials of 
bapineuzumab in mild-to-moderate Alzheimer’s Disease patients. J Alzheimers Dis. 
2017;57(2):557-573.
Lichtenstein L, Ron Y, Kivity S, Ben-Horin S, Israeli E, Fraser GM, Dotan I, Chowers Y, 
Confino-Cohen R, Weiss B. Infliximab-related infusion reactions: systematic review. J Chron 
Colitis. 2015;9(9):806-815.
Lim YY, Ellis KA, Ames D, Darby D, Harrington K, Martins RN, Masters CL, Rowe C, Savage 
G, Szoeke C, Villemagne VL, Maruff P; and the AIBL Research Group. Aβ amyloid, 
cognition, and APOE genotype in healthy older adults. Alzheimers Dement. 2013a;9:538-545.
Lim YY, Ellis KA, Harrington K, Pietrzak RH, Gale J, Ames D, Bush AI, Darby D, Martins RN, 
Masters CL, Rowe CC, Savage G, Szoeke C, Villemagne VL, Maruff P, for the AIBL 
Research Group. Cognitive decline in adults with amnestic mild cognitive impairment and 
high Aβ amyloid: prodromal Alzheimer’s disease? J Alzheimers Dis. 2013b;33(4):1167-1176.
Liu-Seifert H, Anderson S, Case M, Sparks J, Holdridge KC, Wessels AM, Hendrix S, Aisen P, 
Siemers E. Statistical properties of continuous composite scales and implications for drug 
development. J Biopharm Stats. 2017, DOI: 10.1080/10543406.2017.1315819
Maruff P, Thomas E, Cysique L, Brew B, Collie A, Snyder P, Pietrzak RH. Validity of the 
CogState brief battery: relationship to standardized tests and sensitivity to cognitive 
impairment in mild traumatic brain injury, schizophrenia, and AIDS dementia complex. Arch 
Clin Neuropsychol. 2009;24(2), 165–178.
Maruff P, Lim YY, Darby D, Ellis KA, Pietrzak RH, Snyder PJ, Bush AI, Szoeke C, Schembri 
A, Ames D, Masters CL, and for the AIBL Research Group. Clinical utility of the cogstate 
brief battery in identifying cognitive impairment in mild cognitive impairment and 
Alzheimer’s disease. BMC Pharmacol Toxicol. 2103;1(1):30. doi: 10.1186/2050-7283-1-30.
May PC, Dean RA, Lowe SL, Martenyi F, Sheehan SM, Boggs LN, Monk SA, Mathes BM, 
Mergott DJ, Watson BM, Stout SL, Timm DE, Smith Labell E, Gonzales CR, Nakano M, Jhee 
SS, Yen M, Ereshefsky L, Lindstrom TD, Calligaro DO, Cocke PJ, Greg Hall D, Friedrich S, 
Citron M, Audia JE. Robust central reduction of amyloid-beta in humans with an orally 
available, non-peptidic beta-secretase inhibitor. J Neurosci. 2011; 31(46): 16507-16516.

I5T-MC-AACG(d) Clinical Protocol
Page 90
LY3002813
McLaughlin T, Feldman H, Fillit H, Sano M, Schmitt F, Aisen P, Leibman C, Mucha L, Ryan 
JM, Sullivan SD, Spackman DE, Neumann PJ, Cohen J, Stern Y. Dependence as a unifying 
construct in defining Alzheimer’s disease severity. Alzheimers Dement. 2010;6(6):482-493.
Mohs RC, Knopmann D, Petersen RC, Ferris SH, Ernesto C, Grundman M, Sano M, 
Bieliauskas L, Geldmacher D, Clark C, Thal LJ. Development of cognitive instruments for use 
in clinical trials of antidementia drugs: additions to the Alzheimer’s Disease Assessment Scale 
that broaden its scope. The Alzheimer’s Disease Cooperative Study. Alzheimer Dis Assoc 
Disord. 1997;11(Suppl 2):S13-S21.
Nathan, PJ, Boardley, R, Scott, N, Berges, A, Maruff, P, Sivananthan, T, Upton N, Lowy MT, 
Nestor PJ, Lai, R. The safety, tolerability, pharmacokinetics and cognitive effects of 
GSK239512, a selective histamine H3 receptor antagonist in patients with mild to moderate 
Alzheimer’s disease: a preliminary investigation. Current Alzheimer Res. 2013;10:240-251.
Ostrowitzki S, Deptula D, Thurfjell L, Barkhof F, Bohrmann B, Brooks DJ, Klunk WE, Ashford 
E, Yoo K, Xu Z-X, Loetscher H, Santarelli L. Mechanism of amyloid removal in patients with 
Alzheimer disease treated with gantenerumab. Arch Neurol. 2012;69(2):198-207.
Qian J, Hyman BT, Betensky RA. Neurofibrillary tangle stage and the rate of progression of 
Alzheimer symptoms: modeling using an autopsy cohort and application to clinical trial 
design. JAMA Neurol. 2017;74:540-548.
Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer’s disease. Am J Psychiatry. 
1984;141(11):1356-1364.
Selkoe DJ. The origins of Alzheimer disease: a is for amyloid. JAMA. 2000;283:1615-1617.
Siemers ER, Sundell KL, Carlson C, Case M, Sethuraman G, Liu-Seifert H, Dowsett SA, 
Pontecorvo MJ, Dean RA, DeMattos R. Phase 3 solanezumab trials: Secondary outcomes in 
mild Alzheimer's disease patients. Alzheimers Dement. 2016;12:110-120.
Spackman DE, Kadiyala S, Neumann PJ, Veenstra DL, Sullivan SD. The validity of dependence 
as a health outcome measure in Alzheimer’s disease. Am J Alzheimers Dis Other Demen. 
2013;28(3):245-252.
Sperling RA, Jack CR Jr, Black SE, Frosch MP, Greenberg SM, Hyman BT, Scheltens P, 
Carrillo MC, Thies W, Bednar MM, Black RS, Brashear HR, Grundman M, Siemers ER, 
Feldman HH, Schindler RJ. Amyloid-related imaging abnormalities in amyloid-modifying 
therapeutic trials: recommendations from the Alzheimer's Association Research Roundtable 
Workgroup. Alzheimers Dement. 2011;7(4):367-385.
Sperling R, Salloway S, Brooks DJ, Tampieri D, Barakos J, Fox NC, Raskind M, Sabbagh M, 
Honig LS, Porsteinsson AP, Lieberburg I, Arrighi HM, Morris KA, Lu Y, Liu E, Gregg KM, 
Brashear HR, Kinney GG, Black R, Grundman M. Amyloid-related imaging abnormalities in 
patients with Alzheimer's disease treated with bapineuzumab: a retrospective analysis. 
Lancet Neurol. 2012;11(3):241-249.
Wessels AM, Siemers ER, Yu P, Andersen SW, Holdridge KC, Sims JR, Sundell K, Stern Y, 
Rentz DM, Dubois B, Jones RW, Cummings J, Aisen PS. A Combined Measure of Cognition 
and Function for Clinical Trials: The Integrated Alzheimer’s Disease Rating Scale (iADRS). J 
Prev Alzheimers Dis. 2015;2(4):227-241.

I5T-MC-AACG(d) Clinical Protocol
Page 91
LY3002813
World Medical Association. Declaration of Helsinki – ethical principles for medical research 
involving human subjects. Available at: https://www.wma.net/policies-post/wma-declaration-
of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/. Accessed 
August 27, 2017.

I5T-MC-AACG(d) Clinical Protocol
Page 92
LY3002813
12. Appendices

I5T-MC-AACG(d) Clinical Protocol
Page 93
LY3002813
Appendix 1.
Abbreviations and Definitions
Term
Definition
Aβ
amyloid β
AD
Alzheimer’s disease
ADA
anti-drug antibodies
ADAS-COG13
Alzheimer’s Disease Assessment Scale – Cognitive subscale 13
ADCS-ADL
Alzheimer’s Disease Cooperative Study—Activities of Daily Living Inventory
ADCS-bADL
Alzheimer’s Disease Cooperative Study—basic activities of daily living
ADCS-iADL
Alzheimer’s Disease Cooperative Study—instrumental activities of daily living
AE
adverse event:  Any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product that does not necessarily have a causal 
relationship with this treatment.  An adverse event can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a medicinal (investigational) product, whether or 
not related to the medicinal (investigational) product.
ALT
alanine aminotransferase
APOE
Apolipoprotein subtype E
ARIA-E
amyloid-related imaging abnormalities–edema/effusions (also known as vasogenic 
edema)
ARIA-H
amyloid-related imaging abnormalities–hemorrhage/hemosiderin deposition (also 
known as cerebral microhemorrhage)
AST
aspartate aminotransferase
BACE
β-site amyloid precursor protein cleaving enzyme
blinding/masking
A single-blind study is one in which the investigator and/or his staff are aware of the 
treatment but the patient is not, or vice versa, or when the sponsor is aware of the 
treatment but the investigator and/his staff and the patients are not.
A double-blind study is one in which neither the patient nor any of the investigator or 
sponsor staff who are involved in the treatment or clinical evaluation of the subjects are 
aware of the treatment received.
BMI
body mass index

I5T-MC-AACG(d) Clinical Protocol
Page 94
LY3002813
bpm
beats per minute
CBB
CogState Brief Battery
CDR-SB
Clinical Dementia Rating Scale – Sum of Boxes 
CIOMS
Council for International Organizations of Medical Sciences
Companion diagnostic 
An in vitro diagnostic device (assay or test) that provides information that is essential 
for the safe and effective use of a corresponding therapeutic product
complaint
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of a drug or drug delivery system.
compliance
Adherence to all study-related, good clinical practice (GCP), and applicable regulatory 
requirements.
CRF
case report form
CRP
clinical research physician:  Individual responsible for the medical conduct of the study.  
Responsibilities of the CRP may be performed by a physician, clinical research 
scientist, global safety physician or other medical officer.
C-SSRS
Columbia Suicide Severity Rating Scale
CTCAE
Common Terminology Criteria for Adverse Events
CYP3A
cytochrome P450 3A
DMC
data monitoring committee
ECG
electrocardiogram
eCOA
Electronic Clinical Outcome Assessment
ED
early discontinuation
ELISA
enzyme-linked immunosorbent assay
End of Study
End of the study is the date of the last visit or last scheduled procedure shown in 
the Schedule of Activities (Section 2) for the last patient.
enroll
The act of assigning a patient to a treatment.  Patients who are enrolled in the study are 
those who have been assigned to a treatment.
enter
Patients entered into a study are those who sign the informed consent form directly or 
through their legally acceptable representatives.
FAS
full analysis set
FDA
Food and Drug Administration
GCP
good clinical practice

I5T-MC-AACG(d) Clinical Protocol
Page 95
LY3002813
HBsAg
hepatitis B surface antigen
HCG
human chorionic gonadotropin
HCV
hepatitis C virus
IAC
internal assessment committee
iADRS
integrated Alzheimer’s Disease Rating Scale (iADRS)
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation
Informed consent
A process by which a patient voluntarily confirms his or her willingness to participate 
in a particular study, after having been informed of all aspects of the study that are 
relevant to the patient’s decision to participate.  Informed consent is documented by 
means of a written, signed and dated informed consent form.
interim analysis
An interim analysis is an analysis of clinical study data, separated into treatment groups, 
that is conducted before the final reporting database is created/locked.
investigational 
product
A pharmaceutical form of an active ingredient or placebo being tested or used as a 
reference in a clinical trial, including products already on the market when used or 
assembled (formulated or packaged) in a way different from the authorized form, or 
marketed products used for an unauthorized indication, or marketed products used to 
gain further information about the authorized form.
ITT
intention to treat:  The principle that asserts that the effect of a treatment policy can be 
best assessed by evaluating on the basis of the intention to treat a patient (i.e., the 
planned treatment regimen) rather than the actual treatment given.  It has the 
consequence that patients allocated to a treatment group should be followed up, 
assessed, and analyzed as members of that group irrespective of their compliance to the 
planned course of treatment.
IVRS/IWRS
interactive voice-response system/interactive web-response system
MedDRA
Medical Dictionary for Regulatory Activities  
MHIS
Modified Hachinski Ischemic Scale
MMRM
mixed-model repeated-measures
MMSE
Mini-Mental State Examination
MOA
mechanism of action
MRI
magnetic resonance imaging
NIA-AA
National Institute on Aging (NIA) and the Alzheimer’s Association (AA)
No
number

I5T-MC-AACG(d) Clinical Protocol
Page 96
LY3002813
PCR
polymerase chain reaction
PET
positron emission tomography
PHF
paired helical filament deposits
PK/PD
pharmacokinetics/pharmacodynamics
PPS
per-protocol set:  The set of data generated by the subset of patients who sufficiently 
complied with the protocol to ensure that these data would be likely to exhibit the 
effects of treatment, according to the underlying scientific model.
PRO/ePRO
patient-reported outcomes/electronic patient-reported outcomes
Q2WK
once every 2 weeks
Q4WK
once every 4 weeks
QD
once a day
QW
once a week
QT
QT interval on the ECG
QTc
corrected QT interval
QTcF
Fridericia’s corrected QT interval
RBC
red blood cell
SAE
serious adverse event
SAP
statistical analysis plan
screen
The act of determining if an individual meets minimum requirements to become part of 
a pool of potential candidates for participation in a clinical study. 
SHSF
Self-Harm Supplement form
SPF
skin protection factor
SUSARs
suspected unexpected serious adverse reactions
TE
treatment-emergent
TEADA
treatment-emergent anti-drug antibody
TEAE
treatment-emergent adverse event:  An untoward medical occurrence that emerges 
during a defined treatment period, having been absent pretreatment, or worsens relative 
to the pretreatment state, and does not necessarily have to have a causal relationship 
with this treatment.
V
visit

I5T-MC-AACG(d) Clinical Protocol
Page 97
LY3002813
WBC
white blood cell
Wk
week
WOCBP
women of child-bearing potential

I5T-MC-AACG(d) Clinical Protocol
Page 98
LY3002813
Appendix 2.
Clinical Laboratory Tests
Clinical Laboratory Tests
Hematologya,b
Clinical Chemistrya,b,c
Hemoglobin
Serum Concentrations of:
Hematocrit
Sodium
Erythrocyte count (RBC)
Potassium
Mean cell volume
Total bilirubin
Mean cell hemoglobin concentration
Direct bilirubin
Leukocytes (WBC)
Alkaline phosphatase (ALP)
Neutrophils, segmented
Alanine aminotransferase (ALT)
Lymphocytes
Aspartate aminotransferase (AST)
Monocytes
Blood urea nitrogen (BUN)
Eosinophils
Creatinine
Basophils
Uric acid
Platelets
Calcium
Glucose, nonfasting 
Urinalysisa,b
Albumin
Specific gravity
Cholesterol
pH
Creatine kinase (CK)
Protein
Other Tests
Glucose
Human chorionic gonadotropin (HCG) (females)d,e,f
Ketones
APOE genotypinga,c,g
Blood
High sensitivity C-reactive proteinc
Urine leukocyte esterase
Calculated creatinine clearance (Cockcroft and Gault 
1976)
HBsAgh
HCV RNA PCRi
Immune Safety Labsj
Β tryptase
Total Immunoglobulin E
Immune complex testing
Abbreviations:  RBC = red blood cells; WBC = white blood cells.
a
Assayed by Lilly-designated (central) laboratory.
b
Results will be confirmed by the Lilly-designated (central) laboratory at the time of initial testing.
c
Samples collected for specified laboratory tests will be destroyed within 60 days of receipt of confirmed test 
results.  Certain samples may be retained for a longer period, if necessary, to comply with applicable laws, 
regulations, or laboratory certification standards.
d
Females of childbearing potential are to have a central lab serum pregnancy test (HCG) at V1.  The serum 
pregnancy test will need to be repeated if the screening period lasts more than 63 days.
e
Females of childbearing potential are to have a local urine pregnancy test (HCG) on the day of flortaucipir F18 
PET imaging before the scan is done to confirm they are not pregnant.
f
Females of childbearing potential are to have a local urine pregnancy test (HCG) on the day of florbetapir F18 
PET imaging before the scan is done to confirm they are not pregnant.

I5T-MC-AACG(d) Clinical Protocol
Page 99
LY3002813
g
Neither patients nor investigators will receive the genotype results unless there is a country-specific law or 
regulation that requires notification of the results.  Failure to collect samples for APOE genotyping will not be 
considered a protocol deviation if country-specific regulations prohibit the testing of genetic material or 
transportation of such material outside of the country.
h
laboratory test to be performed only for patients with a past history of Hepatitis B
i
laboratory test to be performed only for patients with a past history of Hepatitis C
j
laboratory tests to be performed only for patients with moderate to severe infusion reaction (see Section 9.4.7.1.2
for timing of sample collection).

I5T-MC-AACG(d) Clinical Protocol
Page 100
LY3002813
Appendix 3.
Study Governance Considerations

I5T-MC-AACG(d) Clinical Protocol
Page 101
LY3002813
Appendix 3.1. Regulatory and Ethical Considerations, Including the 
Informed Consent Process
Appendix 3.1.1.
Informed Consent
The investigator is responsible for:

ensuring that the subject/subject’s legal representative understands the nature of the 
study, the potential risks and benefits of participating in the study, and that their 
participation is voluntary.

ensuring that informed consent is given by each subject or legal representative.  This 
includes obtaining the appropriate signatures and dates on the ICF prior to the 
performance of any protocol procedures and prior to the administration of investigational 
product.

answering any questions the subject/ subject’s legal representative may have throughout 
the study and sharing in a timely manner any new information that may be relevant to 
the subjects/ subject’s legal representative’s willingness to continue his or her 
participation in the study.

ensuring that a copy of the ICF is provided to the subject or the subject’s legal 
representative and is kept on file.

ensuring that the medical record includes a statement that written informed consent was 
obtained before the subject was enrolled in the study and the date the written consent 
was obtained.  The authorized person obtaining the informed consent must also sign the 
ICF.
Study partners will also sign the informed consent.  If it is not known that the study partner will 
change, the new study partner would need to sign the ICF when he/she takes over the care for the 
subject and study participation.  The change in study partner would also need to be documented 
on the eCRF.
As used in this protocol, the term “informed consent” includes all consent and assent given by 
subject or their legal representatives and by study partners.
Appendix 3.1.2.
Recruitment
Lilly or its designee is responsible for the central recruitment strategy for subjects.  Individual 
investigators may have additional local requirements or processes.
Appendix 3.1.3.
Ethical Review
The investigator or an appropriate local representative must give assurance that the ethical 
review board (ERB) was properly constituted and convened as required by International Council 
for Harmonisation (ICH) guidelines and other applicable laws and regulations.
Documentation of ERB approval of the protocol and the ICF must be provided to Lilly before the 
study may begin at the investigative site(s).  Lilly or its representatives must approve the ICF, 
including any changes made by the ERBs, before it is used at the investigative site(s).  All ICFs 
must be compliant with the ICH guideline on Good Clinical Practice (GCP).

I5T-MC-AACG(d) Clinical Protocol
Page 102
LY3002813
The study site’s ERB(s) should be provided with the following:

the protocol and related amendments and addenda, current Investigator 
Brochure (IB) and updates during the course of the study

informed consent form

other relevant documents (e.g., curricula vitae, advertisements)
Appendix 3.1.4.
Regulatory Considerations
This study will be conducted in accordance with the protocol and with the:

consensus ethics principles derived from international ethics guidelines, including 
the Declaration of Helsinki and Council for International Organizations of
Medical Sciences (CIOMS) International Ethical Guidelines

applicable ICH GCP Guidelines

applicable laws and regulations
Some of the obligations of the sponsor will be assigned to a third-party.
Appendix 3.1.5.
Investigator Information
Physicians with expertise in neurology, geriatrics, or psychiatry who have clearly documented 
extensive experience in AD trials will participate as investigators in this clinical study.  In 
addition, licensed clinicians who have clearly documented extensive experience in AD trials may 
participate as investigators in this clinical study upon approval by the Sponsor.  Contact 
information for investigators, clinical laboratories, and other medical and/or technical 
department(s) and/or institutions involved in the clinical study is maintained in the study records.
Cognitive assessments must be administered by an individual trained in the use of these 
instruments.  Investigators and site personnel who will perform ratings will be trained and 
approved by Lilly or its designee prior to participating in the study.  In most cases, evaluation 
and notification will occur at the investigator meeting.  Individuals who do not attend the rater 
evaluation and training portion of the investigator meeting and who wish to perform the ratings 
in this study must be evaluated and approved by Lilly or its designee prior to performing any 
ratings.  Note that the ADAS-Cog and MMSE must be administered by different rater than the 
ADCS-ADL and CDR.  These 2 raters should continue doing the same scale with the same 
patient throughout the study.  These 2 or 3 raters should continue doing the same scale with the 
same patient throughout the study.  If possible, the measurements should be performed on a 
given patient by the same rater at each visit.  The PI has the responsibility of selecting who will 
administer the instruments at the site, as long as all training requirements have been met by those 
raters.

I5T-MC-AACG(d) Clinical Protocol
Page 103
LY3002813
Appendix 3.1.6.
Protocol Signatures
The sponsor’s responsible medical officer will approve the protocol, confirming that, to the best 
of his or her knowledge, the protocol accurately describes the planned design and conduct of the 
study.
After reading the protocol, each principal investigator will sign the protocol signature page and 
send a copy of the signed page to a Lilly representative.
Appendix 3.1.7.
Final Report Signature
The CSR coordinating investigator will sign the final CSR for this study, indicating agreement 
that, to the best of his or her knowledge, the report accurately describes the conduct and results 
of the study.
The investigator with the most qualified subjects will serve as the CSR coordinating investigator.  
If this investigator is unable to fulfill this function, another investigator will be chosen by Lilly to 
serve as the CSR coordinating investigator.
The sponsor’s responsible medical officer and statistician will approve the final CSR for this 
study, confirming that, to the best of his or her knowledge, the report accurately describes the 
conduct and results of the study.
Appendix 3.2.
Data Quality Assurance
To ensure accurate, complete, and reliable data, Lilly or its representatives will do the following:

provide instructional material to the study sites, as appropriate

sponsor investigator study site trainings to instruct the investigators and study 
coordinators.  This training will give instruction on the protocol, the completion 
of the CRFs, and study procedures.

make periodic visits to the study site

be available for consultation and stay in contact with the study site personnel by 
mail, telephone, and/or fax

review and evaluate eCRF data and use standard computer edits to detect errors in 
data collection

conduct a quality review of the database
In addition, Lilly or its representatives will periodically check a sample of the subject data 
recorded against source documents at the study site.  The study may be audited by Lilly or its 
representatives, and/or regulatory agencies at any time.  Investigators will be given notice before 
an audit occurs.
The investigator will keep records of all original source data.  This might include laboratory 
tests, medical records, and clinical notes.  If requested, the investigator will provide the sponsor, 
applicable regulatory agencies, and applicable ERBs with direct access to original source 
documents.

I5T-MC-AACG(d) Clinical Protocol
Page 104
LY3002813
Appendix 3.2.1.
Data Capture System
An electronic data capture system will be used in this study.  The site maintains a separate source 
for the data entered by the site into the sponsor-provided electronic data capture system.
Electronic Clinical Outcome Assessment (eCOA) measures (e.g., a rating scale, including audio 
voice recordings of the rater’s questions and the patient’s and study partner’s responses) are 
entered into an eCOA instrument (at the time that the information is obtained).  The eCOA tablet 
has both keyboard entry and audio voice recording capabilities.  In these instances where there is 
no prior written or electronic source data at the site, the eCOA instrument record will serve as the 
source.
If eCOA records are stored at a third party site, investigator sites will have continuous access to 
the source documents during the study and will receive an archival copy at the end of the study 
for retention.
Any data for which the eCOA instrument record will serve to collect source data will be 
identified and documented by each site in that site’s study file.
Case report form data will be encoded and stored in a clinical trial database.  Data managed by a 
central vendor, such as audio voice recordings, laboratory test data, or ECG data, will be stored 
electronically in the central vendor’s database system.  With the exception of the audio voice 
recordings, which are only used for central monitoring purposes, data will subsequently be 
transferred from the central vendor to the Lilly data warehouse.
Any data for which paper documentation provided by the subject will serve as the source 
document will be identified and documented by each site in that site’s study file.
Data from complaint forms submitted to Lilly will be encoded and stored in the global product 
complaint management system.
Appendix 3.3.
Study and Site Closure
Appendix 3.3.1.
Discontinuation of Study Sites
Study site participation may be discontinued if Lilly or its designee, the investigator, or the ERB 
of the study site judges it necessary for medical, safety, regulatory, or other reasons consistent 
with applicable laws, regulations, and GCP.
Appendix 3.3.2.
Discontinuation of the Study
The study will be discontinued if Lilly or its designee judges it necessary for medical, safety, 
regulatory, or other reasons consistent with applicable laws, regulations, and GCP.
Appendix 3.4.
Publication Policy
The publication policy for Study AACG is described in the Clinical Trial Agreement.

I5T-MC-AACG(d) Clinical Protocol
Page 105
LY3002813
Appendix 4.
Hepatic Monitoring Tests for Treatment-
Emergent Abnormality
Selected tests may be obtained in the event of a treatment-emergent hepatic abnormality and may 
be required in follow-up with patients in consultation with the Lilly, or its designee, clinical 
research physician.
Hepatic Monitoring Tests
Hepatic Hematologya
Haptoglobina
Hemoglobin
Hematocrit
Hepatic Coagulationa
RBC
Prothrombin Time
WBC
Prothrombin Time, INR
Neutrophils, segmented
Lymphocytes
Hepatic Serologiesa,b
Monocytes
Hepatitis A antibody, total
Eosinophils
Hepatitis A antibody, IgM
Basophils
Hepatitis B surface antigen
Platelets
Hepatitis B surface antibody
Hepatitis B Core antibody
Hepatic Chemistrya
Hepatitis C antibody
Total bilirubin
Hepatitis E antibody, IgG
Direct bilirubin
Hepatitis E antibody, IgM
Alkaline phosphatase
ALT
Anti-nuclear antibodya
AST
GGT
Alkaline Phosphatase Isoenzymesa
CPK
Anti-smooth muscle antibody (or anti-actin 
antibody)a
Abbreviations:  ALT = alanine aminotransferase; AST = aspirate aminotransferase; CPK = creatinine 
phosphokinase; GGT = gamma-glutamyl transferase; Ig = immunoglobulin; INR = international normalized 
ratio; RBC = red blood cells; WBC = white blood cells.
a
Assayed by Lilly-designated or local laboratory.
b
Reflex/confirmation dependent on regulatory requirements and/or testing availability.

I5T-MC-AACG(d) Clinical Protocol
Page 106
LY3002813
Appendix 5.
Flortaucipir F18 Tau PET Imaging
A screening flortaucipir F18 PET scan will be performed as part of the study eligibility criteria.  
An additional flortaucipir F18 PET scan will be performed at Visit 21 or at early discontinuation 
(if ED occurs more than 36 weeks after randomization Visit 2).
“Specific instructions for the flortaucipir F18 PET scan itself will be provided in the PET 
Imaging Manual.
Inclusion Criteria for Flortaucipir F18 PET Scans
With the exception of the MRI and florbetapir F18 PET scan, a patient should meet all other 
Visit 1 eligibility criteria before having a flortaucipir F18 PET scan.
[1] For female patients of childbearing potential, a negative urine pregnancy (HCG) test must be 
observed on the day of flortaucipir F18 imaging before beginning imaging procedures.
Exclusion Criteria for Flortaucipir F18 PET Scans
A patient will be excluded from participation in flortaucipir F18 imaging if he or she meets any 
of the criteria below:
[2] Has any condition that, in the investigator’s opinion, could increase risk to the patient, limit 
the patient’s ability to tolerate the experimental procedures, or interfere with analysis of the 
data.  (For example, patients with chronic back pain might not be able to lie still during the 
scanning procedures.)
[3] Has abnormal findings on physical examination, laboratory screening tests, or screening  
ECGs that suggest the patient might have a condition that could, in the opinion of the 
investigator, affect his or her response to the radiopharmaceutical and related testing 
procedures.
[4] Is deemed likely to be unable to complete the imaging procedure for any reason.
[5] Is receiving other radiation exposure that, when added to the flortaucipir F18 PET scan, 
would exceed local or national regulatory limits for a patient.
Site investigators, patients, and study partners will not be informed of the results of PET scans 
obtained following randomization, as they relate to the study.  Any findings that may be of 
potential medical concern will be provided for appropriate follow-up.

I5T-MC-AACG(d) Clinical Protocol
Page 107
LY3002813
PET Scan-Specific Information
PET Scan Procedures
Specific imaging acquisition protocols designed to ensure consistency across sites will be 
provided in an PET Imaging Manual.  The scanning technologists will be blinded to patients’ 
treatment assignments.
Scan Safety
The primary risk related to flortaucipir F18 PET is radiation exposure.  Details on the amount of 
exposure estimated to occur on each imaging occasion and cumulatively are shown in Table 
APP.5.1 and will be provided in the ICF.  In addition, the tau ligand flortaucipir F18 continues to 
be in clinical evaluation, and risks from the agent are not fully known.  Details on the clinical 
information to date regarding flortaucipir F18 exposure will be provided in the ICF.  More 
detailed information about the known and expected benefits and risks of flortaucipir F18 may be 
found in the Investigator’s Brochure.
Patients must minimize movement during each PET procedure, which can last 10 to 30 minutes 
for each scan.  Most state-of-the-art imaging systems are designed to reduce head motion and 
patient discomfort.
Table APP.5.1.
Effective Radiation Dose (mSv)
Effective 
Dose 
(mSv) per 
Scan*
Number of 
Scans in 
First 
Year**
Effective 
Dose (mSv) 
for Scans in 
First Year
Number 
of Scans 
in Second 
Year**
Effective 
Dose (mSv) 
for Scans in 
Second Year
Effective 
Dose (mSv) 
for   Years 1 
and 2
Flortaucipir F 18 
Scan (10 mCi iv)
9.10
1
9.10
1
9.10
18.20
Florbetapir F 18 
Scan (10 mCi iv)
7.43
2
14.86 
2
14.86
29.72 
Totals
3
23.96
3
23.96
47.92
Abbreviations:  CT = computerized tomography; IV = intravenous infusion; PET = positron emission tomography.
*Dose shown includes radiation exposure from the radiotracer and also assumes a non-clinical CT scan is obtained 
(estimated at 0.4 mSv) as part of the PET scan attenuation correction process when the scan is done on a PET/CT 
scanner.  A clinical CT scan is not needed during the PET scan session and because it will add additional 
radiation exposure is not recommended.
** In the event that the patient is discontinued from the Study AACG, the subject will be asked to participate in a 
discontinuation visit.  A flortaucipir F18 scan will not be done at the ET visit if it has been ≤12 weeks since the 
previous scan.
In the case of early discontinuation from Study AACG, the final flortaucipir F18 PET scan will 
be obtained at the time of the early discontinuation visit (ED) if at least 36 weeks have passed 
since the most recent flortaucipir F18 PET scan.

I5T-MC-AACG(d) Clinical Protocol
Page 108
LY3002813
Visits that include imaging should be completed over adjacent days.  Note that florbetapir F18 
PET amyloid imaging and flortaucipir F18 PET tau imaging can be performed 1 or 2 days after 
cognitive and functional testing and additional timing considerations apply:

flortaucipir F18 PET scans should be performed at least 16 hours apart from the 
florbetapir F18 PET scans due to the half-life of fluorine 18.
With respect to other compound-related risks, flortaucipir was positive in the in vitro hERG
assay.  Although the margin of safety appears high, and in vivo cardiovascular assessments in 
dogs showed no evidence of QT prolongation, subjects with a history of risk factors for torsades 
de pointes and patients taking drugs known to prolong the QT interval will be excluded from this 
study.
If it becomes necessary for a patient to start taking a medication known to prolong QT interval 
prior to performance of any postbaseline flortaucipir F18 scan, do not perform the scan.  The 
patient may, however remain in the study.  Nonperformance of postbaseline flortaucipir F18 PET 
scans in patients taking a medication known to prolong QT interval will not be considered a 
protocol deviation.

I5T-MC-AACG(d) Clinical Protocol
Page 109
LY3002813
Appendix 6.
Florbetapir F18 Amyloid PET Imaging
Screening florbetapir F18 PET scans will be performed as part of the study eligibility criteria to 
determine patient eligibility for participation in Study AACG.  Additional florbetapir F18 PET 
scans will be performed at Visit 8 (Week 24), Visit 15 (Week 52), and Visit 21 (Week 76) or at 
early discontinuation (if ED occurs more than 8 weeks after the previous visit at which a 
florbetapir F18 PET scan was done).  Specific instructions for the florbetapir F18 PET scan itself 
will be provided in the PET Imaging Manual.
Inclusion Criteria for Florbetapir F18 PET Scans
With the exception of the MRI, a patient should meet all other Visit 1 eligibility criteria before 
having a florbetapir F18 PET scan.
[1]
For female patients of childbearing potential, a negative urine pregnancy 
(HCG) test must be observed on the day of florbetapir F18 PET imaging 
before beginning imaging procedures.
Exclusion Criteria for Florbetapir F18 PET Scans
A patient will be excluded from participation in florbetapir F18 PET amyloid imaging if he or 
she meets any of the criteria below:
[2]
Has any condition that, in the investigator’s opinion, could increase risk to the 
patient, limit the patient’s ability to tolerate the experimental procedures, or 
interfere with analysis of the data. (For example, patients with chronic back 
pain might not be able to lie still during the scanning procedures.)
[3]
Has abnormal findings on physical examination, laboratory screening tests, or 
screening MRI or ECGs that suggest the patient might have a condition that 
could, in the opinion of the investigator, affect his or her response to the 
radiopharmaceutical and related testing procedures.
[4]
Is deemed likely to be unable to complete the imaging procedure for any 
reason.
[5]
Is receiving other radiation exposure that, when added to the florbetapir F18
PET scan, would exceed local or national regulatory limits for a patient.
Site investigators, patients, and study partners will not be informed of the results of PET scans 
obtained following randomization, as they relate to the study.  Any findings that may be of 
potential medical concern will be provided for appropriate follow-up.

I5T-MC-AACG(d) Clinical Protocol
Page 110
LY3002813
PET Scan-Specific Information
PET Scan Procedures
Specific imaging acquisition protocols designed to ensure consistency across sites will be 
provided in a PET Imaging Manual.  The scanning technologists will be blinded to patients’ 
treatment assignments.
PET Scan Safety
The primary risk related to florbetapir F18 PET is radiation exposure.  Details on the amount of 
exposure estimated to occur on each imaging occasion and cumulatively are presented in Table 
APP.5.1 above and will be provided in the ICF.  Details on the clinical information to date 
regarding florbetapir F18 exposure will be provided in the ICF.  More detailed information about 
the known and expected benefits and risks of florbetapir F18 may be found in the United States 
Package Insert for florbetapir F18 Injection (AmyvidTM).
Patients must minimize movement during each PET procedure, which can last 10 to 30 minutes 
for each scan.  Most state-of-the-art imaging systems are designed to reduce head motion and 
patient discomfort.
In the case of early discontinuation from Study AACG, the final florbetapir F18 PET scan will 
be obtained at the time of the early discontinuation visit (ED) if at least 8 weeks have passed 
since the most recent florbetapir F18 PET scan.
Visits that include imaging should be completed over adjacent days.  Note that florbetapir F18 
PET amyloid imaging and flortaucipir F18 PET tau imaging can be performed 1 or 2 days after 
cognitive and functional testing and additional timing considerations apply:

florbetapir F18 PET scans should be performed at least 16 hours apart from the
flortaucipir F18 PET scan due to the half-life of fluorine 18.

I5T-MC-AACG(d) Clinical Protocol
Page 111
LY3002813
Appendix 7.
Protocol Amendment [I5T-MC-AACG(c)] 
Summary [Assessment of Safety, Tolerability, and 
Efficacy of LY3002813 in Early Symptomatic Alzheimer’s 
Disease]
Overview
Protocol I5T-MC-AACG Assessment of Safety, Tolerability, and Efficacy of LY3002813 in 
Early Symptomatic Alzheimer’s Disease has been amended.  The new protocol is indicated by 
amendment (d) and will be used to conduct the study in place of any preceding version of the 
protocol.
The main changes to this protocol include removing LY3202626 as a combination therapy.
The overall changes and rationale for the changes made to this protocol are described in the 
following table.  Note that minor edits have been made throughout the protocol, which are not 
captured in the amendment summary table.

I5T-MC-AACG(d) Clinical Protocol
Page 112
LY3002813
Amendment Summary for Protocol I5T-MC-AACG Amendment (d)
Section # and Name
Description of Change
Brief Rationale
Title page
Removed mention of LY3202626 and combination 
therapy.  Added amendment (d) to the list of 
amendments. Changed date of current protocol.
To reflect the content of the current amendment.
Section 1. Synopsis
Changed study title and removed mention of 
LY3202626 and combination therapy from the 
study description and the study objectives.  
Changed numbers of patients to reflect the 
elimination of the LY3202626 treatment arm.
Deleted the row for “Evaluable” under 
“Approximate Number of Patients.”
To reflect the elimination of the LY3202626 
treatment arm.
Deleted to prevent confusion. Details are provided 
in Section 10.
Section 2. Schedule of Activities
Removed ophthalmological and dermatological 
exams from screening assessments and changed 
timing of these assessments during the treatment 
period to reflect the elimination of the LY3202626 
treatment arm.  Removed mention of LY3202626 
administration, compliance checks, and plasma PK 
sampling.  Deleted the column for Visit 22, as this 
visit is no longer needed. 
To reflect the elimination of the LY3202626 
treatment arm.
Section 3. Introduction
Removed mention of LY3202626 as part of the 
combination.  Removed background specific to 
LY3202626 and its mechanism of action.
To reflect the elimination of the LY3202626 
treatment arm.
Section 3.2.2. LYL3002813 Phase 1 Studies
Updated information about ongoing Phase 1b 
single- and multiple-dose study I5T-MC-AACD 
(Study AACD).
To provide updated information about this ongoing 
study.
Section 4. Objectives and Endpoints
Removed mention of LY3202626 and combination 
therapy from the study objectives.  Removed 
ophthalmological and dermatological examinations 
from safety endpoints.
To reflect the elimination of the LY3202626 
treatment arm.
Section 5. Study Design
Removed mention of LY3202626 and combination 
therapy from the study design.  Added description 
of screening policy for patients in active screening 
To reflect the elimination of the LY3202626 
treatment arm.

I5T-MC-AACG(d) Clinical Protocol
Page 113
LY3002813
Section # and Name
Description of Change
Brief Rationale
prior to implementation of amendment (d).  
Changed duration of double-blind period to 76 
weeks, with up to 72 weeks of treatment. Modified 
study design illustration and visits throughout.
Changed number of study participants.  
Removed ophthalmological and dermatological 
evaluation from Screening.
To delete examinations and visit no longer needed 
after elimination of the LY3202626 treatment arm.
Section 5.1. Overall Design
Changed “124-week study” to “133-week study.”
Correction
Section 5.1.3. Immunogenicity and Safety 
Follow-up Visits (Visit 801)
Changed heading to “Immunogenicity and Safety 
Follow-up Visits (Visits 801 through 804)”
Clarification (made consistent with text)
Section 6.1. Inclusion Criteria
From Inclusion Criterion #4, deleted the bullet 
regarding study partners being available by 
telephone for CDR and ADCS-ADL.
Correction; this scale is not administered over the 
phone.
Section 6.2. Exclusion Criteria
From Exclusion Criterion #11, deleted “retinal” 
from the list of exclusionary conditions.
Deleted Exclusion Criterion #18, #32, #37, #56, and 
#57.
To remove criteria specific to LY3202626.
Section 6.3. Lifestyle Restrictions
Restrictions #2 and #3 were removed.
To remove restrictions specific to LY3202626.
Section 7. Treatments
Deleted mention of LY3202626 dosage, 
administration, and packaging. 
To reflect the elimination of the LY3202626 
treatment arm.
Section 8. Discontinuation Criteria
Deleted ophthalmological and dermatological
examinations as a factor in permanent treatment 
discontinuation.  Rephrased discontinuation to 
remove mention of discontinuing one treatment but 
continuing the other.  Deleted criteria specific to 
discontinuing treatment with LY3202626.  Changed 
timing of follow-up after early discontinuation visit.
To reflect the elimination of the LY3202626 
treatment arm.
Section 9. Study Assessments and Procedures
Deleted administration of LY3202626. Removed 
AESIs specific to LY3202626.  Deleted information 
To reflect the elimination of the LY3202626 
treatment arm.

I5T-MC-AACG(d) Clinical Protocol
Page 114
LY3002813
Section # and Name
Description of Change
Brief Rationale
about treatment of LY3202626 overdose.  Edited 
text about ophthalmological and dermatological 
examinations to clarify that these will be done only 
in patients who received LY3202626 or oral 
placebo and only at 1 visit (scheduled or 
unscheduled) after the final dose of 
LY3202626/oral placebo.  Deleted information 
about PK sampling for LY3202626.
Added statements about completing CRFs for 
hypersensitivity and ARIA-E.
In Section 9.1 (and Appendix 3.1.5), changed the 
statement that ADAS-Cog and MMSE “should” be 
administered by a different rater than ADCS-ADL 
and CDR to “must” be administered by a different 
rater.
Clarification
Clarification
Section 10. Statistical Considerations
Changed numbers of patients and power 
calculations to reflect the elimination of the 
LY3202626 treatment arm.  Deleted mentions of 
combination therapy.  Provided information about 
how data from patients previously randomized to 
LY3202626 treatment will be handled.
To reflect the elimination of the LY3202626 
treatment arm.

I5T-MC-AACG(d) Clinical Protocol
Page 115
LY3002813
Revised Protocol Sections
Note:
Deletions have been identified by strikethroughs.
Additions have been identified by the use of underscore.
The numbering system used for inclusion and exclusion criteria provides a unique number for 
each criterion and allows for efficiency in data collection.
In case an amendment to the protocol adds a criterion, that criterion will receive the next 
available number, regardless of whether it is an inclusion or exclusion criterion.
Title Page
Protocol I5T-MC-AACG(dc) Assessment of Safety, Tolerability, and Efficacy of 
LY3002813 Alone and in Combination with LY3202626 in Early Symptomatic 
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 LY3002813 and 
LY3002813/LY3202626 combination, unless such persons are bound by 
a confidentiality agreement with Eli Lilly and Company or its subsidiaries.
LY3002813
&
LY3202626
Multicenter, randomized, double-blind, placebo-controlled, Phase 2 study 
comparing up to 1400 mg of LY3002813 alone and in combination with 
12 mg of LY3202626 with placebo over 7680 weeks in approximately 
250300 patients with early symptomatic AD.
Section 1. Synopsis
Title of Study:
Protocol I5T-MC-AACG(c).  Assessment of Safety, Tolerability and Efficacy of LY3002813 
Alone and in Combination with LY3202626 in Early Symptomatic Alzheimer’s Disease.

I5T-MC-AACG(d) Clinical Protocol
Page 116
LY3002813
Rationale:
This study evaluates use of two anti-amyloid therapies with different mechanisms of action 
targeting the amyloid cascade.  LY3002813 is an antibody directed at the pyroglutamate 
modification of the third amino acid of amyloid beta (N3pG Aβ) epitope that is present only in 
brain amyloid plaques.  It is being studied for the treatment of Alzheimer’s disease (AD).  The 
mechanism of action of LY3002813 is considered to be the targeting and removal of existing 
amyloid plaque, which is a key pathological hallmark of AD.  The clinical strategy for 
LY3002813 targets the N3pG Aβ specific to amyloid plaque in the population of early 
symptomatic AD patients with existing brain amyloid load, as measured using the amyloid 
plaque biomarker, florbetapir F18 positron emission tomography (PET) imaging.  
ThisLY3202626 is a synthetic small molecule, an inhibitor of β-site amyloid precursor protein 
(APP)-cleaving enzyme [BACE]1, being assessed for the treatment of AD in an ongoing phase 2 
study.  The mechanism of action of LY3202626 is considered to be the reduction of Aβ 
monomer production through BACE 1 inhibition.  Combination therapy rationale is based on the 
amyloid hypothesis of AD, which states that the production and deposition of Aβ is an early and 
necessary event in the pathogenesis of AD (Selkoe 2000).  Clinical support for this hypothesis 
comes from the demonstration that parenchymal Aβ levels are elevated before the appearance of 
symptoms of AD, and supported by genetic variants of AD that overproduce brain Aβ and 
genetic variants that protect against Aβ production (Jonsson et al. 2012; Fleisher et al. 2015).  
Furthermore, early in the disease, the presence of brain amyloid appears to increase the risk of 
conversion from mild cognitive impairment (MCI) to AD dementia (Doraiswamy et al. 2012).  
This suggests that enhanced clearance of Aβ will lead to slowing of AD progression.
This study, I5T-MC-AACG (AACG), is evaluating LY3002813 alone or in combination with 
LY3202626 compared with placebo.  There is evidence suggesting that different forms of 
amyloid (monomeric, oligomeric and insoluble plaques) may all contribute neurotoxicity 
independently (Selkoe 2008).  Animal models suggest that treatment with a combination of a 
BACE inhibitor and an anti-plaque antibody will reduce soluble forms of amyloid and contribute 
to a greater reduction of deposited plaques compared with a plaque-specific antibody alone 
(Jacobsen et al. 2014).  This may also provide synergistic effects on plaque removal compared to 
either drug given independently with more rapid and quantitatively greater amyloid removal 
(DeMattos 2016).  Increased and more rapid removal of amyloid plaque plus removal of soluble 
forms of amyloid by parallel administration of both LY3002813 and LY3202626 over time is 
therefore hypothesized to have the potential for greater clinical efficacy than either drug given 
alone, with broader target engagement.  Combination of therapeutics has been standard of care in 
most disease clinical practices, such as oncology, cardiology, and endocrinology.  Of late, there 
has been much discussion of the need for combination therapies in AD, as an ultimate path 
toward finding beneficial treatments for patients (Hendrix 2016).
Study I5T-MC-AACG (AACG) is a Phase 2, double-blind, placebo-controlled, study to evaluate 
the safety and efficacy of N3pG antibody (LY3002813) alone or in combination with BACE 
inhibitor (LY3202626) in patients with early symptomatic AD (prodromal AD and mild 
dementia due to AD).  Study AACG will assess whether removal of existing amyloid plaque 

I5T-MC-AACG(d) Clinical Protocol
Page 117
LY3002813
alone or in combination with lowering of Aproduction via BACE inhibition can slow the 
progression of disease as assessed by clinical measures and biomarkers of disease pathology and 
neurodegeneration over up to 7276 weeks of treatment.
Multiple biomarkers of disease progress will also be evaluated.  The biomarker florbetapir F18 is 
a PET ligand that binds to fibrillar amyloid plaque.  This biomarker can provide a qualitative and 
quantitative measurement of brain plaque load in patients with prodromal AD or mild AD 
dementia.  The absence of significant florbetapir F18 signal on a visual read indicates that those 
patients clinically manifesting cognitive impairment have sparse to no amyloid plaques.  As 
such, implementation of florbetapir F18 will provide a screening tool for entry into the clinical 
trialtrials and provide a confirmation of amyloid pathology.  Florbetapir F18 PET also provides 
quantitative assessment of fibrillar amyloid plaque in the brain and can assess amyloid plaque 
reductions from the brain by LY3002813 and in combination with BACE inhibition with 
LY3202626.
Objective(s)/Endpoints:
Primary Objective
Primary Endpoint
To test the hypothesis that LY3002813 alone 
and/or in combination with LY3202626
administered for up to 7276 weeks will decrease 
the cognitive and/or functional decline in 
patients with early symptomatic AD
Change in cognition and function as measured by the 
change in integrated Alzheimer’s Disease Rating Scale 
(iADRS) score from baseline to 18 months
Secondary Objectives
Secondary Endpoints
To assess the effect of LY3002813 alone and in 
combination with LY3202626 vs. placebos on 
clinical progression in patients with early 
symptomatic AD
Change in cognition from baseline to 18 months as 
measured by:

the change in Alzheimer’s Disease Assessment 
Scale—Cognitive subscale (ADAS-Cog13) 
score

the change in Clinical Dementia Rating Scale 
Sum of Boxes (CDR-SB) score

the change in Mini-Mental State Examination 
(MMSE) score

the change in Alzheimer’s Disease Cooperative 
Study-instrumental Activities of Daily Living 
scale (ADCS-iADL) score 
To assess the effect of LY3002813 alone and in 
combination with LY3202626 vs. placebo on 
brain amyloid deposition
Change in brain amyloid plaque deposition from 
baseline through 18 months as measured by florbetapir
F18 PET scan  
To assess the effect of LY3002813 alone and in 
combination with LY3202626 vs. placebo on 
brain tau deposition
Change in brain tau deposition from baseline to 18 
months as measured by flortaucipir F18 PET scan  
To assess the effect of LY3002813 alone and in 
combination with LY3202626 vs. placebo on 
brain volume measures
Change in volumetric MRI measures from baseline to 
18 months.

I5T-MC-AACG(d) Clinical Protocol
Page 118
LY3002813
To assess the effect of combination therapy with 
LY3002813 and LY3202626 vs LY3002813 
alone on clinical progression in patients with 
early symptomatic AD
Change from baseline to 18 months in iADRS score, 
ADAS-Cog13 score, CDR-SB score, MMSE score, 
ADCS-iADL score
Safety Objective
Safety Endpoints
To evaluate safety and tolerability of 
LY3002813 alone and in combination with 
LY3202626

Standard safety assessments:
o
spontaneously reported adverse events 
(AEs)
o
clinical laboratory tests
o
vital sign and body weight 
measurements
o
12-lead ECGs
o
physical and neurological 
examinations

MRI (amyloid-related imaging abnormalities 
[ARIAs] and emergent radiological findings)

Skin examination

Eye examination

Columbia Suicide Severity Rating Scale
(C-SSRS)
Summary of Study Design:
Study AACG is a multicenter, randomized, double-blind, placebo-controlled, Phase 2 study of 
LY3002813 alone and in combination with LY3202626 in subjects with early symptomatic AD.  
The 133124-week study includes a screening period of up to 9 weeks, a treatment period of up to
7276 weeks with final evaluations occurring 4 weeks later at Week 76, and , a 484-week 
posttreatment follow-up, and a 44-week immunogenicity and safety follow-up period.
Treatment Arms and Duration:
Patients will receive the following treatments for up to 7276 weeks:

LY3002813 monotherapy (LY3002813-M):  intravenous LY3002813 (700 mg Q4WK 
for the first 3 doses, then 1400 mg Q4WK) for up to 72 weeks,in combination with daily 
oral placebo,

LY3002813 in combination with LY3202626 (LY3002813-C):  intravenous LY3002813 
(700 mg Q4WK for the first 3 doses, then 1400 mg Q4WK) in combination with daily 
oral LY3202626 (12 mg), or

Placebo:  intravenous placebo Q4WK for up to 72 weeksin combination with daily oral 
placebo.
Abbreviations:  C = combination therapy; M = monotherapy

I5T-MC-AACG(d) Clinical Protocol
Page 119
LY3002813
Approximate Number of Patients:
Screened – 1497
Randomized – 266375
Evaluable –300 (approximately 100 per treatment group)
Statistical Analysis:
Efficacy:
The primary objective of this study is to test the hypothesis that intravenous infusion of 
LY3002813 alone or in combination with LY3202626 will slow the cognitive and/or functional 
decline of AD as measured by the composite measure iADRS compared with placebo in patients 
with early symptomatic AD.  The change from baseline score on the iADRS at each scheduled 
postbaseline visit during the treatment period will be analyzed using an MMRM model, which 
includes the following terms:  baseline score, pooled investigator, treatment, visit, treatment-by-
visit interaction, baseline-by-visit interaction, concomitant AChEI and/or memantine use at 
baseline (yes/no), and age at baseline.  The primary time point for treatment comparison will be 
at the end of the double blind treatment period (Week 76).  The treatment group contrast in least-
squares mean progression and its associated p-value and 95% CI will be calculated for the
treatment comparison of LY3002813-C vs. placebo and LY3002813-M vs. placebo.  In addition, 
Bayesian posterior probability of the active treatment arm being superior to placebo by at least a 
margin of interest (25% slowing of placebo progression) will also be calculated.
Pharmacokinetics/Pharmacodynamics:
Compartmental modeling of LY3002813 and LY3202626 PK data using nonlinear mixed effects 
modeling or other appropriate software may be explored, and population estimates for clearance 
and central volume of distribution may be reported.  Depending on the model selected, other PK 
parameters may also be reported.  Exploratory graphical analyses of the effect of dose level or 
demographic factors on PK parameters may be conducted.  If appropriate, data from other 
studies of LY3002813 or LY3202626 may be used in this analysis.
Pharmacokinetic/pharmacodynamic (PK/PD) relationships between plasma LY3002813 
concentration and SUVr, cognitive endpoints, ARIA incidence rate or other markers of PD 
activity may be explored graphically.  The relationship between the presence of antibodies to 
LY3002813 and PK, PD, safety and/or efficacy may be assessed graphically.  The effect of 
LY3202626 exposure on SUVr, cognitive endpoints, or other markers of PD activity may also be 
explored graphically.  Graphical and/or descriptive analyses may be explored to evaluate 
potential interactions between LY3002813 and LY3202626 for PK.  If warranted, additional 
analysis may be explored to evaluate potential interactions for ADA, PD and other endpoints 
(PET scan, ARIA-E, etc.).  Additional modeling may be performed based on the results of the 
graphical analyses.
Section 2. Schedule of Activities

I5T-MC-AACG(d) Clinical Protocol
Page 120
LY3002813
Schedule of Activities Protocol - I5T-MC-AACG Visit 1 (Screening Period)
Period:
Procedure
Visit No.:
V1
End of Week Relative to Study Medication Starta
Wk -9 through Wk -1
Tolerance Interval for Visit (days)a,b
63
PRELIMINARY SCREENING
Entry Diagnostics 
  MMSEc,d,su
X
SCREENING
  Ophthalmological examinationf
X
  Dermatological examinationg
X
Safety Assessments
   Vital signsfh
X
   Height and Wweightgi
X
   ECG in triplicatehj
X
   C-SSRS/SHSF/SHFUi,jk,l
X
Laboratory Specimens
  Human chorionic gonadotropin (HCG) (if applicable)k,l,m,n,o
Xb
  HBsAgnp
X
  HCV RNA PCRoq
X
Screening PET Scans and MRI
   Flortaucipir F18 PET Sscanl,pn,r
X
   MRIqs
X
   Florbetapir F18 PET scanb,m,ro,t
X

I5T-MC-AACG(d) Clinical Protocol
Page 121
LY3002813
Abbreviations:  HBsAg = hepatitis B surface antigen; HCV = hepatitis C virus; MRI = Mmagnetic Rresonance 
Iimaging; PCR = polymerase chain reaction; SHFU = Self-Harm Follow-Up.
a
The interval between V1 and V2 may be up to 63 days to allow for completion of V1 screening procedures, 
assessments, and evaluation of results from laboratory tests and ECGs.  V1 is not considered complete until all 
screening procedures have been completed and results reviewed by the investigator to determine patient 
eligibility.  V1 may be conducted over more than 1 day.  Subjects in screening at the time screening was paused 
are allowed to continue screening beyond the 63 days to allow for completion of V1 screening procedures; this 
will not be a protocol deviation.  Additional details are provided in Section 5.1.1.  Subjects who had completed 
screening but were not yet randomized at the time randomization was paused are allowed to be randomized 
beyond 63 days; this will not be a protocol deviation.  Additional details are provided in Section 5.1.1.
b
A florbetapir F18 PET scan is the final screening criterion for establishing patient eligibility, although the MRI, 
ophthalmological and dermatological exams may be performed after the florbetapir F18 PET scan.  Patients 
whose screening florbetapir F18 PET scan results are not available within the 63 day screening window will 
remain eligible within V1 until these results become available if all other eligibility criteria have been met.  Note:  
If a patient’s screening florbetapir F18 PET scan result confirming eligibility for the study has not been received 
by the site by Day 63 of the screening period, then repeat the following laboratory tests:  blood hematology, 
chemistry, and serum pregnancy test (HCG) for women of childbearing potential (WOCBP).  Results of the 
repeated labs are to be reviewed by the investigator or qualified designee for assessment of the patient’s 
continued eligibility.  Repeat screening for MMSE, CBB, C-SSRS, ECG, dermatological and ophthalmological 
examinations, flortaucipir F18 PET, MRI, and laboratory testing for HBsAg, and HCV RNA PCR is not 
required.  V1 is not considered complete until all screening procedures have been completed and results reviewed 
by the investigator or qualified designee to determine patient eligibility.
c
A preliminary screening informed consent may be obtained to conduct initial screening to collect demographics 
data and administer the MMSE and CBB.  Patients who do not meet the  MMSE screening criteria are not to 
have any other screening procedures performed with the exception of the CBB.  The CBB should be 
administered to all patients at the screening visit, regardless of the MMSE score.  They may be rescreened for the 
MMSE 8 weeks after the first screen.  Study partners are not required to complete the preliminary screening 
informed consent.
d
Patients who meet the MMSE screening criteria may proceed to the remaining screening procedures once they 
have given signed/dated informed consent for the full study and their study partner has given signed/dated 
informed consented to participate as a study partner.
e
A complete physical and neurological exam is to be performed at this visit.  Additional details are provided in 
Section 9.4.1.
f
Eye examinations must be conducted by an ophthalmologist or optometrist (where permitted by law).  Additional 
details are provided in Section 9.4.6.3.
g
Skin examinations must be conducted by a dermatologist.  Additional details are provided in Section 9.4.6.4
fh Sitting Bblood pressure and pulse will be measured after 5 minutes in the sitting position only.  Temperature will 
be collected with sitting vital signs.
gi Height and weight will be measured with shoes removed.
hj ECGs should be taken in triplicate at approximately 1-minute intervals.  ECGs should be collected at 
approximately the same time of day, as much as possible, to minimize diurnal variation.
ik The baseline version of the C-SSRS is to be administered at V1.  Patients at imminent risk of suicide (positive 
response to question 4 or 5 on the C-SSRS) will be excluded from participating in the study.

I5T-MC-AACG(d) Clinical Protocol
Page 122
LY3002813
jl
The Self-Harm Supplement formSHSF is completed after each C-SSRS administration to enter the number of 
discrete events of suicidal behavior identified.  If, based on administration of the C-SSRS, it is determined that 
suicide-related behaviors have occurred, then the Self Harm Follow-Up (SHFU) form will be used to collect 
additional information to allow for a more complete assessment of these behaviors.
km Females of childbearing potential are to have a serum pregnancy test (HCG) at V1 (if applicable).
ln Females of childbearing potential are to have a urine pregnancy test (HCG) on the day of flortaucipir F18 PET 
imaging before the flortaucipir F18 dose is administered.
mo Females of childbearing potential are to have a urine pregnancy test (HCG) on the day of florbetapir F18 PET 
imaging before the florbetapir F18 dose is administered.
np Patients with a past history of Hepatitis B are to have a serum HBsAg test at screening V1 and are excluded if the 
HBsAg test is positive.
oq Patients with a past history of Hepatitis C are to have a HCV RNA PCR test at screening V1 and are excluded if 
the HCV RNA PCR test is positive.
pr A screening flortaucipir F18 PET scan will be performed as part of the study eligibility criteria at all sites to 
determine patient eligibility for participation in Study AACG (see Appendix 5).  With the exception of an MRI 
and a florbetapir F18 PET scan, ophthalmological, and dermatological exams, a patient should meet all other V1 
eligibility criteria before having a screening flortaucipir F18 PET scan.  The flortaucipir F18 PET scan will be 
submitted to a centralized PET imaging vendor designated by Lilly for an assessment of patient’s eligibility.  A 
historical flortaucipir F18 PET scan may be submitted to be considered for eligibility if performed within 6 
months of V1.
qs A local screening MRI will be performed at V1 as part of the study eligibility criteria.  With the exception of the 
evidence of amyloid pathology by florbetapir F18 PET scan, and ophthalmological and dermatological exams, a 
patient should meet all other V1 eligibility criteria before having an MRI scan.  The MRI scans will be reviewed 
by the investigator or qualified designee for immediate patient management.  After the MRI scan is read locally, 
the scan is to be submitted to the centralized MRI vendor designated by Lilly for final determination of MRI 
eligibility.  Results of centrally read MRIs will be used for data analysis and report-writing purposes and patient 
safety and eligibility will be reported back to sites.
rt A screening florbetapir F18 PET scan will be performed as part of the study eligibility criteria to determine 
patient eligibility for participation in Study AACG (see Appendix 6).  With the exception of an MRI and 
ophthalmological and dermatological exams, a patient should meet all other V1 eligibility criteria before having a 
screening florbetapir F18 PET scan.  The PET scan will be submitted to a centralized PET imaging vendor 
designated by Lilly for assessment of patient’s eligibility.  The florbetapir F18 PET screening criteria must be 
met (scan results consistent with the presence of amyloid pathology) in order for the patient to proceed to V2 and 
be randomized to treatment assignment.
su Assessment is to include the audio voice recording of the rater’s questions and the patient and caregiver 
responses to assessment questions.

I5T-MC-AACG(d) Clinical Protocol
Page 123
LY3002813
Schedule of Activities, Protocol I5T-MC-AACG, Visit 2 through Visit 14 (Double-Blind Period)
Period:
Procedure
Rand
Visit No.:
V2a,b
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
V13
V14
End of Week Relative to Study Medication Start
0
4
8
12
16
20
24
28
32
36
40
44
48
Tolerance Interval for Visit (days)
0
7
7
7
7
7
7
7
7
7
7
7
7
Inclusion/exclusion review
X
X
X
X
X
X
X
X
X
X
X
X
X
   Contact IWRS – dispensation of study medication
   (LY3002813 and LY3202626)
Xe
X
X
X
X
X
X
X
X
X
X
X
X
   Physical/neurological examinationef
Xfg
Xfg
Xfg
Xgh
   Ophthalmological examinationhi
jk
Xh
Xh
X
   Dermatological examinationij
jk
Xi
Xi
   Previous/concomitant medications
X
X
X
X
X
X
X
X
X
X
X
X
X
   Preexisting conditions/adverse eventsef
X
X
X
X
X
X
X
X
X
X
X
X
X
   LY3002813 study medication administeredk   
Assess LY3202626 compliance
X
X
X
X
X
X
X
X
X
X
X
X
X
   LY3202626 study medication administered at site t
X
X
   LY3002813 Study medication administeredl
X
X
X
X
X
X
X
X
X
X
X
X
X
Efficacy Measures
   ADAS-Cog13
l,ffm,jj
X
X
X
X
   ADCS-ADLl,ffm,jj
X
X
X
X
   CDR-SBl,ffm,jj
X
X
X
X
   MMSEl,ffm,jj
X
X
X
Safety Assessment
   C-SSRS/SHSF/SHFUm,no
  mn
X
X
X
X
X
X
X
X
X
X
X
X

I5T-MC-AACG(d) Clinical Protocol
Page 124
LY3002813
Schedule of Activities, Protocol I5T-MC-AACG, Visit 2 through Visit 14 (Double-Blind Period)
Period:
Procedure
Rand
Visit No.:
V2a,b
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
V13
V14
End of Week Relative to Study Medication Start
0
4
8
12
16
20
24
28
32
36
40
44
48
Tolerance Interval for Visit (days)
0
7
7
7
7
7
7
7
7
7
7
7
7
Laboratory Specimensop
   Clinical chemistry, hematologypq
X
X
X
X
X
X
   High sensitivity C-reactive proteinpq
X
X
X
X
X
X
   Urinalysispq
X
   Serum for anti-LY3002813 antibodypq
X
X
X
X
X 
X
X
   Serum LY3002813q,rr,s
Xq
Xrs
Xrs
Xqr
Xrs
Xqr
Xrs
   Plasma LY3202626t,u,v
Xt, u
Xv
Xv
Xt, u
Xv
Xv
   Blood for assessment of APOE genotypep,sq,w
X
   Whole blood, plasma and serum for biomarker 
storagep,tq,x
X
X
X
X
   Blood for pharmacogenomicsp,t,uq,x,y
X
Other Safety Measures
   Weight
X
X
X
X
   Vital signs and temperaturev,wz,aa
Xwaa
X
X
Xwaa
X
X
Xwaa
X
X
Xwaa
X
X
X
   ECG in triplicatexbb
X
X
X
X
X
X
   MRIycc
zdd
X
Xaaee
X
X
X
Additional Efficacy Measures
  Flortaucipir F18 PET scanbb,ccff,gg
zdd
  Florbetapir F18 PET scanbb,ddff,hh
zdd
Xbb,ddff,
hh

I5T-MC-AACG(d) Clinical Protocol
Page 125
LY3002813
Schedule of Activities, Protocol I5T-MC-AACG, Visit 15 through Visit 2122 (Double-Blind Period) and Follow-Up
Period:
Procedure
Visit No.:
V15
V16
V17
V18
V19
V20
V21
V22
EDc
V801-
V804d,eeii
End of Week Relative to Study Medication Start
52
56
60
64
68
72
76
80
88-124
Tolerance Interval for Visit (days)
7
7
7
7
7
7
7
7
14
   Inclusion/exclusion review
X
X
X
X
X
X
X
   Contact IWRS – dispensation of study medications
   (LY3002813 and LY3202626)
X
X
X
X
X
X
  
  
   Physical/neurological examinationef
Xfg
Xgh
Xfg
Xg
Xfg
   Ophthalmological examinationh,ji
X
X
Xh
   Dermatological examinationi,jj
X 
X
Xi
   Previous/concomitant medications
X
X
X
X
X
X
X
X
X
X
   Preexisting conditions/adverse eventsef
X
X
X
X
X
X
X
X
X
X
   Assess LY3202626 compliance
X
X
X
X
X
X
X
X
   LY3002813 Sstudy medication administeredkl
X
X
X
X
X
X
Efficacy Measures
   ADAS-Cog13
l,ffm,jj
X
X
X
X
   ADCS-ADLl,ffm,jj
X
X
X
X
   CDR-SBl,ffm,jj
X
X
X
X
   MMSEl,ffm,jj
X
X
X
X
Safety Assessment
   C-SSRS/SHSF/SHFUm,no
X
X
X
X
X
X
X
X
X
X

I5T-MC-AACG(d) Clinical Protocol
Page 126
LY3002813
Schedule of Activities, Protocol I5T-MC-AACG, Visit 15 through Visit 2122 (Double-Blind Period) and Follow-Up
Period:
Procedure
Visit No.:
V15 V16
V17
V18
V19
V20
V21
V22
EDc
V801-
V804d,eeii
End of Week Relative to Study Medication 
Start
52
56
60
64
68
72
76
80
88-124
Tolerance Interval for Visit (days)
7
7
7
7
7
7
7
7
14
Laboratory Specimensop
   Clinical chemistry, hematologypq
X
X
X
X
X
   High sensitivity C-reactive proteinpq
X
X
X
X
X
   Urinalysispq
X
X
X
X
X
   Serum for anti-LY3002813 antibodypq
X
X
X
X
   Serum LY3002813p,q,rr,s
Xqr
Xrs
Xqr
Xrs
Xrs
Xrs
   Plasma LY3202626t,u,v
Xv
Xv
Xv
Xv
   Blood for assessment of APOE genotypep,sq,w
   Whole blood, plasma and serum for biomarker 
storagep,tq,x
X
X
X
X
   Blood for pharmacogenomicsp,t,uq,x,y
Other Safety Measures
   Weight
X
X
X
X
X
   Vital signs and temperaturev,wz,aa
Xwaa
X
X
Xwaa
X
X
Xwaa
Xaa
X Xaa
X 
   ECG in triplicatexbb
X
X
X
X
X
   MRIycc
X
X
X
Additional Efficacy Measures
   Flortaucipir F18 PET Scanbb,ccff,gg
Xbb,ccff,
gg
Xbb,ccff,
gg
   Florbetapir F18 PET scanbb,ddff,hh
Xbb,
ddff,h
h
Xbb,ddff,
hh
Xbb,ccff,
gg

I5T-MC-AACG(d) Clinical Protocol
Page 127
LY3002813
Schedule of Activities, Protocol I5T-MC-AACG, Visit 2 through Visit 2122 (Double-Blind Period) and 
Follow-Up Abbreviations and Footnotes
Abbreviations:  APOE = aApolipoprotein subtype E; ARIA-E = amyloid related imaging abnormalities–
edema/effusions
a
Confirm that the patient has met all V1 eligibility criteria before proceeding with V2 procedures.
b
At V2, appointments should be made for all remaining visits and should be scheduled as close as possible to the 
target date, relative to V2.  Procedures for some visits may take more than 1 day.
c
If a patient discontinues before the double-blind period endpoint (V21V22 at Week 7680), complete the Early 
Discontinuation CRFs.  The patient should be encouraged to return to the site beginning 12 weeks after the ED 
visit for an immunogenicity follow-up visit (Visit 801 through V804).
d
Patients are to return to the site for collection of blood samples and safety assessments for assessment of 
immunogenicity status at Visit 801 (Week 88).  Follow-up for patients experiencing clinically significant events 
associated with TEADA status is described in Section 9.4.7.2.
e
Patients are to take oral study medication (placebo or LY3202626) once per day in the morning.  The first dose 
should be taken the morning after the first dispensing of oral study medication at Visit 2.
ef Any clinically significant changes from baseline on follow-up physical/neurological examinations should be 
noted on the AE page.
fg A complete physical and neurological exam is to be performed at this visit.  Additional details are provided in 
Section 9.4.1.
gh A brief physical and neurological exam is to be performed at this visit.  Additional details are provided in Section 
9.4.1.
h
Eye Ophthalmological examinations will be performed only in patients who previously received LY3202626/oral 
placebo in this study.  The final examination for each patient will be the next scheduled ophthalmological 
examination after the final administration of LY3202626/oral placebo.  It will not be considered a protocol 
deviation if this examination is scheduled sooner than indicated above in order to accommodate patient and/or 
site preference.  Patients who received LY3202626/oral placebo after their V9 ophthalmological examination are 
to have an unscheduled ophthalmological examination at the next available opportunity.  These Eye
examinations must be conducted by an ophthalmologist or optometrist (where permitted by law).  Additional 
details are provided in Section 9.4.6.3.
i
Dermatological examinations will be performed only in patients who previously received LY3202626/oral 
placebo in this study.  The final examination for each patient will be the next scheduled dermatological 
evaluation after the final administration of LY3202626/oral placebo.  It will not be considered a protocol 
deviation if this examination is scheduled sooner than indicated above in order to accommodate patient and/or 
site preference.  Patients who received LY3202626/oral placebo after their V8 dermatological examination are to 
have an unscheduled dermatological examination at the next available opportunity.  These examinations must be 
conducted by a dermatologist.  Additional details are provided in Section 9.4.6.4.
j
For subjects randomized prior to amendment (d), the eye ophthalmological and skin dermatological examination 
performed at screening will serve as the baseline eye ophthalmological and skin dermatological examination.
kl Study drug will be administered by intravenous administration at investigative study site.  Patients should be 
observed for approximately 2 hours following each infusion of LY3002813 for the first 6 infusions.  After the 
first six doses, a minimal post-infusion observation time of 60 minutes will be required for all subsequent 
infusions.  However, patients who have had dosing restarted after ARIA-E are required to be monitored for 
2 hours following infusion for a minimum of 3 subsequent infusions, and a minimum of 60 minutes post-infusion 
observation thereafter.
lm When administered, cognitive and functional assessments (ADAS-Cog13, ADCS-ADL, CDR, and MMSE) 
should be performed first, before medical procedures that could be stressful for the patient (e.g., blood draws).
mn The C-SSRS administered at screening will serve as the baseline C-SSRS.

I5T-MC-AACG(d) Clinical Protocol
Page 128
LY3002813
no The ‘since last visit’ version of the C-SSRS will be administered at visits after V2 (Week 0) to the patient with 
the study partner/study informant present, after the cognitive and functional assessments.  The Self-Harm 
Supplement form (SHSF) is completed after each C-SSRS administration to enter the number of discrete events 
of suicidal behavior identified.  If, based on administration of the C-SSRS, it is determined that suicide-related 
behaviors have occurred, then the SHFU form will be used to collect additional information to allow for a more 
complete assessment of these behaviors
op Unscheduled laboratory tests may be performed at the discretion of the investigator.
pq Labs are to be collected prior to administration of the intravenous study medication (LY3002813 or IV placebo).  
Record the date and times of sample collection on the Lab Requisition Form.
qr Pre-dose (before beginning the infusion) samples for intravenous study medication (LY3002813) may be 
collected from the intravenous site prior to beginning the infusion. Post-dose (within 30 minutes of completion 
of the infusion) samples for intravenous study medication (LY3002813) should be collected from the arm that 
did not receive the infusion at V2 (Week 0), V5 (Week 12), V8 (Week 24), V15 (Week 52), and V20 (Week 72).
rs A single pre-dose LY3002813 sample should be collected before beginning the infusion at V3 (Week 4), V4 
(Week 8), V6 (Week 16), V11 (Week 36), and V18 (Week 64).  In addition, a single sample for serum 
LY3002813 should be collected at V21 (Week 76), or ED, and V801 (visits at which the patient may not receive 
a study drug infusion).  If LY3002813 infusion is permanently discontinued but the patient remains in the study, 
one PK sample should be collected at the soonest scheduled visit regardless if serum LY3002813 is on the 
Schedule of Activities at that visit.  Subsequent PK sample collection should follow the protocol Schedule of 
Activities for serum LY3002813 collection unless the scheduled visit exceeds 6 months since discontinuation of 
infusions.  No additional serum collection for LY3002813 is required once the patient exceeds 6 months since 
discontinuation of LY3002813 infusions.  Record the actual date and times of sample collection on the Lab 
Requisition Form.
t
Prior to V3 (Week 4) and V6 (Week 16), a phone call should be made approximately 1 business day before the 
clinic visit to remind patients to hold the morning dose of oral study medication (LY3202626) on the day of the 
visit and to bring the dose to the clinic.
u
Pre-dose (before taking oral study medication) and post-dose (prior to the patient departing the site) samples for 
oral study medication (LY3202626) should be collected at V3 (Week 4) and V6 (Week 16).  Record the date and 
times of sample collection on the Lab Requisition Form.  The actual time of LY3202626 dose administrations on 
the day of study visits will be recorded in the subject’s case report form (CRF).  In addition, the actual time of 
LY3202626 dose administration for the 2 days prior to each visit at which LY3202626 PK samples will be 
collected will be recorded in the subject’s CRF.
v
A single LY3202626 sample should be collected at V4 (Week 8), V5 (Week 12), V8 (Week 24), V11 (Week 36), 
V15 (Week 52), V18 (Week 64), and V21 (Week 76) or ED.  Record the date and times of sample collection on 
the Lab Requisition Form.  The actual time of LY3202626 dose administrations on the day of study visits will be 
recorded in the subject’s CRF.  If LY3202626 is permanently discontinued but the patient remains in the study, a 
final sample should be collected, provided the last dose of LY3202626 is within 3 days of the visit.  No other PK 
samples for LY3202626 are required after the final sample.  In addition, the actual time of LY3202626 dose 
administration for the 2 days prior to each visit at which LY3202626 PK samples will be collected will be 
recorded in the subject’s CRF.
sw A blood sample will be collected to determine APOE genotype.  The APOE genotype sample may be collected at 
an alternative visit if it cannot be collected at V2.
tx Blood for biomarker storage, and blood for pharmacogenomic samples are to be collected unless not allowed or 
unfeasible due to local regulations prohibiting sample transport outside of the country.
uy Pharmacogenomic samples may be collected at an alternative visit if they cannot be collected at V2.  It will not 
be a protocol deviationviolation if a biomarker storage sample cannot be collected for technical reasons (e.g., if 
the site is unable to collect enough blood via venipuncture).
vz Sitting blood pressure and pulse will be measured after 5 minutes in the sitting position at all visits.  Temperature 
will be collected with sitting vital signs.

I5T-MC-AACG(d) Clinical Protocol
Page 129
LY3002813
waa
In addition, orthostatic blood pressure and pulse will be measured at V2 (Week 0), V5 (Week 12), V8 
(Week 24), V11 (Week 36), V15 (Week 52), V18 (Week 64), V21 (Week 76), V22 (Week 80) or ED, and at 
unscheduled visits after 5 minutes in the supine position and after 3 minutes standing.
xbbElectrocardiograms should be taken in triplicate at approximately 1-minute intervals.  ECGs should be collected 
at approximately the same time of day, as much as possible, to minimize diurnal variation.  ECGs are to be 
performed prior to the administration of intravenous study medication (LY3002813 and IV placebo).
ycc If MRI is done on the same day as cognitive and functional assessments, then it should be done after cognitive 
and functional tests.  MRI may be done before other visit procedures, including cognitive and functional tests, 
but in that case must be done at least 1 day before other visit procedures.
zddThe screening flortaucipir F18 PET scan, MRI, and florbetapir F18 PET scan done at V1 serve as the baseline 
flortaucipir F18 PET scan, MRI and florbetapir F18 PET scan, respectively.
aaee
The V5 MRI is to be performed 2 weeks prior to the V5 (Week 12) LY3002813 infusion to allow for 
receipt and review of the central vendor MRI report prior to a possible LY3002813 dose change at V5 (Week 
12).
bbff
Females of childbearing potential are to have a urine pregnancy test (HCG) performed on the day of 
florbetapir F18 PET and flortaucipir F18 PET imaging before the florbetapir F18 dose or flortaucipir F18 dose is 
administered to confirm that they are not pregnant.
ccgg
All patients will have a flortaucipir F18 PET scan done at V21 (Week 76) or ED (if ED occurs more than 
36 weeks after randomization) (see Appendix 5).  Before the flortaucipir F18 PET scan, the investigator should 
review the patient’s medical history and concomitant medications to verify there is no risk factor for Ttorsades de 
Ppointes and review the most recent ECG. If clinically meaningful abnormalities are noted on the ECG, the 
advisability of the flortaucipir scan should be considered by the investigator in consultation with the 
Lilly-designated medical monitor. Patients permanently discontinued from LY3202626 study treatment due to 
initiation of a prohibited medication known to prolong the QT-interval should not have an ED flortaucipir scan 
unless the scan can be performed prior to initiation of the prohibited medication.  The study investigator and site 
clinical study team will not have access to the flortaucipir F18 follow-up scans, as the site clinical study team 
must remain blinded to any potential changes in tau deposition.
ddhh
All patients will have double-blind period florbetapir F18 PET scans done at V8 (Week 24), V15 (Week 
52), and V21 (Week 76) or ED (if ED occurs more than 8 weeks after a florbetapir F18 PET scan has been 
performed at a previous visit) (see Appendix 6).  The study investigator and site clinical study team will not have 
access to any florbetapir F18 follow-up scans, as the site clinical study team must remain blinded to any potential 
changes in amyloid deposition.
eeiiPatients are to return to the site for an immunogenicity and safety follow-up visit (Visit 801) at Week 88 (or 12 
weeks after the ED visit) for collection of blood samples for anti-drug antibody (ADA) measurements and 
assessment of adverse events and concomitant medications.  The need for additional study visits after V801 will 
be determined by results of the ADA sample taken at V801.  A patient will stop immunogenicity follow-up visits 
when they either complete 3 additional quarterly visits (Week 100, Week 112, and Week 124) or complete a visit 
at which their ADA returns to baseline (2-fold titer from baseline), whichever occurs first.  See Section 5.1.3 and 
Section 9.4.7.2 for details.
ffjj Assessment is to include the audio voice recording of the rater’s questions and the patient and caregiver 
responses to assessment questions.
3.
Introduction
3.1.
Study Rationale
This study evaluates use of two anti-amyloid therapies with different mechanisms of action 
targeting the amyloid cascade.  LY3002813 is an antibody directed at the pyroglutamate 
modification of the third amino acid of amyloid beta (N3pG Aβ) epitope that is present only in 

I5T-MC-AACG(d) Clinical Protocol
Page 130
LY3002813
brain amyloid plaques.  It is being studied for the treatment of Alzheimer’s disease (AD).  The 
mechanism of action of LY3002813 is considered to be the targeting and removal of existing 
amyloid plaque, which is a key pathological hallmark of AD.  The clinical strategy for 
LY3002813 targets the N3pG Aβ specific to amyloid plaque in the population of early 
symptomatic AD patients with existing brain amyloid load, as measured using the amyloid 
plaque biomarker, florbetapir F18 positron emission tomography (PET) imaging. This 
LY3202626 is a synthetic small molecule, an inhibitor of β-site amyloid precursor protein 
(APP)-cleaving enzyme [BACE]1, being assessed for the treatment of AD in an ongoing phase 2 
study.  The mechanism of action of LY3202626 is considered to be the reduction of Aβ 
monomer production through BACE 1 inhibition.  Combination therapy rationale is based on the 
amyloid hypothesis of AD, which states that the production and deposition of Aβ is an early and 
necessary event in the pathogenesis of AD (Selkoe 2000).  Clinical support for this hypothesis 
comes from the demonstration that parenchymal Aβ levels are elevated before the appearance of 
symptoms of AD, and supported by genetic variants of AD that overproduce brain Aβ and 
genetic variants that protect against Aβ production (Jonsson et al. 2012; Fleisher et al. 2015).  
Furthermore, early in the disease, the presence of brain amyloid appears to increase the risk of 
conversion from mild cognitive impairment (MCI) to AD dementia (Doraiswamy et al. 2012).  
This suggests that enhanced clearance of Aβ will lead to slowing of AD progression.
This study, I5T-MC-AACG (AACG), is evaluating LY3002813, alone or in combination with 
LY3202626, compared with placebo.  There is evidence suggesting that different forms of 
amyloid (monomeric, oligomeric and insoluble plaques) may all contribute to neurotoxicity 
independently (Selkoe 2008).  Animal models suggest that treatment with a combination of a 
BACE inhibitor and an anti-plaque antibody will reduce soluble forms of amyloid and contribute 
to a greater reduction of deposited plaques compared with a plaque-specific antibody alone 
(Jacobsen et al. 2014).  This may also provide synergistic effects on plaque removal compared to 
either drug given independently with more rapid and quantitatively greater amyloid removal
(DeMattos 2016).  Increased and more rapid removal of amyloid plaque plus removal of soluble 
forms of amyloid by parallel administration of both LY3002813 and LY3202626 over time is 
therefore hypothesized to have the potential for greater clinical efficacy than either drug given 
alone, with broader target engagement.  Combination of therapeutics has been standard of care in 
most disease clinical practices, such as oncology, cardiology, and endocrinology.  Of late there 
has been much discussion of the need for combination therapies in AD, as an ultimate path 
toward finding beneficial treatments for patients (Hendrix 2016).
Study I5T-MC-AACG (AACG) is a Phase 2, double-blind, placebo-controlled study to evaluate 
the safety and efficacy of N3pG antibody (LY3002813) alone or in combination with BACE 
inhibitor (LY3202626) in patients with early symptomatic AD (prodromal AD and mild 
dementia due to AD).  Study AACG will assess whether removal of existing amyloid plaque 
alone or in combination with lowering of Aβ production via BACE inhibition can slow the 
progression of disease as assessed by clinical measures and biomarkers of disease pathology and 
neurodegeneration over up to 72 weeks of treatment76 weeks of treatment.  No LY3202626 
monotherapy arm is included in this proof of concept study.  Clinical trials using LY3202626 

I5T-MC-AACG(d) Clinical Protocol
Page 131
LY3002813
and other BACE inhibitors as monotherapies are being conducted which may provide further 
understanding of the safety and efficacy data collected in this study.
Multiple biomarkers of disease progress will also be evaluated.  The biomarker florbetapir F18 is 
a PET ligand that binds to fibrillar amyloid plaque.  This biomarker can provide a qualitative and 
quantitative measurement of brain plaque load in patients with prodromal AD or mild AD 
dementia.  The absence of significant florbetapir F18 signal on a visual read indicates that those 
patients clinically manifesting cognitive impairment have sparse to no amyloid plaques.  As 
such, implementation of florbetapir F18 will provide a screening tool for entry into the clinical 
trials and provide a confirmation of amyloid pathology.  Florbetapir F18 PET also provides 
quantitative assessment of fibrillar amyloid plaque in the brain and can assess amyloid plaque 
reductions from the brain by LY3002813 and in combination with BACE inhibition with 
LY3202626.
3.2.
Background
Alzheimer’s disease is an age-related neurodegenerative disorder characterized by progressive 
decline in cognitive function and the ability to perform activities of daily living, ultimately 
resulting in dementia, typically with fatal complications.  The amyloid hypothesis of AD 
postulates that the accumulation of amyloid-β peptide (Aβ) is an early and necessary event in the 
pathogenesis of AD.  This hypothesis suggests that treatments that slow the accumulation of Aβ 
plaque in the brain or increase clearance of Aβ may be able to slow the progression of the AD 
clinical syndrome.  It is further postulated that combination of treatments that target both 
removal of Aβ plaque in the brain and reduce production of Aβ monomers may have added 
benefit.  The other hallmark neuropathological lesion of AD, intraneuronal neurofibrillary 
tangles consisting of tau proteins, is thought to be another marker for disease progression (Braak 
and Braak 1996).  The relationship between these 2 pathologies is still unclear, although the 
presence of both is necessary for the diagnosis of definite AD.
Amyloid β is part of the APP, which is a transmembrane protein widely expressed on the cell 
surface, particularly in neurons.  The APP has been found to be cleaved through 2 cleavage 
pathways involving 3 secretase enzymes:  -secretase, γ-secretase, and -secretase (now called 
-site APP-cleaving enzyme [BACE]1).  Cleavage of APP by -secretase precludes the 
formation of Aas the site is located within the Asequence.  In the second pathway, 
-secretase cleaves the APP molecule, generating membrane-associated C99 and releasing a 
larger secreted fragment called secreted APP (sAPP).  γ-Secretase then cleaves C99 in a 
heterogeneous fashion within the membrane releasing a variety of Aspecies that aggregate in 
protofibrils, then fibrils, which seem to comprise the mass of Aplaques in AD brain tissue 
(Turner et al. 2003).  While both γ- and β-secretase inhibition represent effective means of 
precluding the formation of A, -secretase inhibition may provide improved safety and 
tolerability (Doody et al. 2013).
3.2.2.LY3002813 Phase 1 Studies
I5T-MC-AACD (Study AACD) is an ongoing Pphase 1b single- and multiple-dose study to 
assess the safety, tolerability, PK, and PD of single and multiple IV doses of LY3002813 in 

I5T-MC-AACG(d) Clinical Protocol
Page 132
LY3002813
patients with mild cognitive impairment due to AD or mild to moderate Alzheimer’s dementia.  
It is evaluatingcurrently enrolling, with up to 150 patients in 6seven different dosing cohorts 
receiving single, every 2 weeks, or every 4 weeks dosing of either 10 mg/kg, 20 mg/kg or 40 
mg/kg of LY3002813.  Treatment durations being assessed include single dose, six month dosing 
every two weeks, or up to 72 weeks of every 4 week dosing.  Safety, PK and PD data from this 
ongoing study are used to inform further development of LY3002813.  See Section 3.3 and the 
IB for detailed safety and PK information regarding LY3002813.
3.2.3.LY3202626 Nonclinical Studies
[Section deleted]
3.2.4.LY3202626 Clinical Studies
[Section deleted]
3.2.5.LY3002813/LY3202626 Combination Therapy - Nonclinical 
Findings
[Section deleted]
3.3.
Benefit/Risk Assessment
3.3.1.Benefit
There is a large unmet medical need for disease-modifying treatments for AD. Data from the 
completed Phase 1a Study AACC Animal models suggest that combination of a BACE inhibitor 
with an anti-plaque antibody will reduce soluble forms of amyloid and from the ongoing Phase 
1b Study AACD indicate a dramaticcontribute to reduction in cerebral amyloid (as assessed by 
florbetapir F18 PET imaging) in individuals who received repeated doses of at least 10 mg/kg 
(IB; Fleisherof insoluble plaques compared to a plaque-specific antibody alone.  This may also 
provide synergistic effects on plaque removal compared to either drug given independently with 
more rapid and quantitatively greater amyloid removal (DeMattos 2016; Hole et al. 2018).  
Along with 2016).  Increased and more rapid removal of amyloid plaque plus removal of soluble 
forms of amyloid by parallel administration of both LY3002813 and LY3202626 over time is 
therefore hypothesized to have greater clinical efficacy than either drug given alone, with 
broader target engagement.
In addition to assessment of safety and tolerability of LY3002813single and combined therapies, 
this study will assess whether removal of existing amyloid plaque alone or in conjunction with 
inhibition of Aproduction in the brain will show evidence of slowed clinical decline and 
change in biomarkers of disease progression relative to placebo treatment.
Although there are currently no available disease-modifying agents for the treatment of AD, 
there are several medications approved by the Food and Drug Administration (FDA) and Health 
Canada for the treatment of symptoms of AD; these include acetylcholinesterase inhibitors (e.g., 
donepezil, galantamine, and rivastigmine) and the N methyl D aspartate receptor antagonist 
memantine.  Because these medications are considered standard of care for the treatment of AD, 

I5T-MC-AACG(d) Clinical Protocol
Page 133
LY3002813
participants in this trial will be permitted to take these medications during the course of the 
study, provided that they have been on a stable dose at the time of randomization and remain on 
a stable dose throughout the study.
3.3.2.Risks
Potential risks (discussed below) for LY3002813 and LY3202626 given alone include, but are 
not limited to,:  1) LY3002813 - formation of anti-drug antibodies (ADA), hypersensitivity 
(immediate and non-immediate, including infusion-related reactions), and amyloid related 
imaging abnormalities (ARIA).) and 2) LY3202626 - hepatic effects, QT prolongation with 
overdose, skin or hair hypopigmentation, rash, retinal changes, and potential interactions with 
other drugs.
LY3002813 – Anti-Drug Antibodies:  High incidences of treatment-emergent anti-drug 
antibodies (TEADAs) have been observed in clinical studies with LY3002813.  Although there 
were no serious adverse events (SAEs) related to the development of ADAs in Study AACC, the 
incidence of TEADAs in LY3002813-exposed patients and subjects was >90 %; in Study 
AACD, the incidence of TEADAs to date (final protocol) in LY3002813-exposed patients and 
subjects is approximately 75 %.  In AACD, on 10 mg/kg Q2WK dosing, one patient was 
observed with a highly elevated ADA titer of 1:163840 on Day 144 postbaseline, with no clinical 
consequences.  Anti-drug antibodies levels may affect PD levels of drug effect.  Infusion 
reactions and ADAs are potential risks common to all large molecules.  See the IB for details 
regarding TEADAs.
LY3002813 –Hypersensitivity (Immediate and Non-immediate,), including infusion-related 
reactions)):  
LY3002813 - Amyloid-Related Imaging Abnormalities:  
LY3202626 - Hepatic effects:  In nonclinical studies, liver enzyme elevations were observed 
with LY3202626 in rats and dogs.  These changes in the 1-month rat and dog studies occurred at 
exposures 245-fold the projected exposure at the high dose (12 mg) in the Phase 2 study.  In the 
6-month toxicology study in rats, mild alanine aminotransferase (ALT)/aspartate 
aminotransferase (AST) increases occurred in the high-dose group; these analytes remained 
increased at similar levels at the end of the 1-month recovery period, indicating lack of 
reversibility.  In the 6-month rat study, ALT/AST increases did not occur at the mid-dose, and 
AUC-based margins at the mid-dose no-observed-adverse-effect level (NOAEL) of 4.5 mg/kg 
are 23- and 6-fold relative to the Phase 2 doses of 3 and 12 mg, respectively.  No liver changes 
occurred in the 9-month toxicology study in dogs (AUC-based margin 39-fold relative to 12-mg 
dose in the Phase 2 study).  Liver-related clinical chemistry analytes will be monitored in the 
clinical trial.  In addition, the investigator may perform additional tests when clinically indicated.  
Clinical manifestations of hepatic injury may include fatigue, jaundice, steatosis, nausea, 
vomiting, right upper quadrant pain or tenderness, fever, rash, or pruritus.
LY3202626 - QT Prolongation:  Dose-dependent QT corrected for heart rate (QTc) prolongation 
(10 to 25 msec) occurred following repeated administration in dogs, at plasma unbound 

I5T-MC-AACG(d) Clinical Protocol
Page 134
LY3002813
maximum observed drug concentration (Cmax) values approximately 3-fold of those projected for 
the highest planned Phase 2 clinical dose of 12 mg.  Specific study exclusion criteria related to 
QTc are defined in the clinical protocol.  Electrocardiograms and vital signs will be carefully 
monitored during the clinical trial.  Cardiac signs and symptoms should be closely monitored in 
the presence of overdose.
LY3202626 - Hypopigmentation:  Dose-dependent decreased pigmentation of the skin and 
haircoat of dogs has been observed in preclinical studies with LY3202626.  The lightening of 
haircoat and mucocutaneous junction epithelium did not impact the well-being of the dogs and 
was reversible during the treatment-free recovery period.  Scheduled skin examinations will be 
performed by a dermatologist in the clinical trial, and are defined in the clinical protocol.  If 
hypopigmentation is observed, patients may continue treatment.  The location of 
hypopigmentation, occurrence of any associated cutaneous changes, and response after the 
treatment period should be monitored.
LY3202626 - Retinal effects:  Adverse retinal effects occurred in both the 1-month and 6-month 
toxicology studies with LY3202626 in rats, which included autofluorescent granule 
accumulation and hypertrophy of the retinal pigmented epithelium with photoreceptor 
degeneration.  In the 6-month rat study, these retinal findings occurred only in the high-dose 
group (25 mg/kg) and did not reverse during the 1-month, treatment-free period.  No retinal 
effects occurred at the NOAEL (4 mg/kg) in the 6-month rat toxicology study, providing area 
under the drug plasma concentration versus time curve (AUC)-based MOS of 23- and 6-fold to 
the Phase 2 doses of 3 and 12 mg.  No adverse retinal changes occurred in dogs.  Scheduled eye 
examinations by an ophthalmologist or optometrist (where permitted by law) will be performed 
in the clinical trial, and are defined in the clinical protocol.  Patients who complain of vision 
disturbance during the clinical trial should be referred to the ophthalmologist or optometrist 
(where permitted by law) for unscheduled evaluation.
LY3202626 - Potential Drug Interactions:  LY3202626 has been shown to be a substrate of 
CYP3A and potentially a time-dependent inhibitor of CYP3A.  Co-administration with a strong 
CYP3A inhibitor led to an approximate 20% increase in LY3202626 exposure, which is not 
thought to be clinically significant.  The effect of LY3202626 on other CYP3A substrates is 
predicted to be modest.  Accordingly, clinically meaningful drug interactions are not anticipated 
with LY3202626 administration.  See the IB for a detailed assessment of clinical and nonclinical 
data regarding the potential for drug interactions.
3.3.3.Benefit/Risk Assessment Summary
To mitigate the potential risks described in Section 3.3.2, the current study will include standard 
safety assessments; i.e., reported AEs, clinical laboratory tests, immunogenicity assessments, 
vital sign and body weight measurements, 12-lead electrocardiograms (ECGs), and physical 
examinations.
Additional safety assessments will include neurological examinations (as part of each physical 
examination), comprehensive eye examinations by an ophthalmologist or optometrist (where 
permitted by law), skin examinations by a dermatologist, MRI examinations, and suicidality 

I5T-MC-AACG(d) Clinical Protocol
Page 135
LY3002813
evaluations using the Columbia-Suicide Severity Rating Scale (C SSRS).  The current study will 
use an independent external Data Monitoring Committee (DMC) to monitor data on an ongoing 
basis to ensure the continuing safety of patients enrolled in this study.
The current study includes placebos of both LY3002813 intravenously and LY3202626 orally as 
a comparator, and approximately one-halfthird of the patients will be randomized to placebo.  In 
addition, all patients participating in the study will have a designated study partner who will have 
regular contact with the patient, accompany the patient to study visits, and liaise with the study 
staff between visits as needed (see Section 6.1 for additional information about the role of the 
study partner).
In conclusion, the available non-clinical and clinical data support the intravenous administration 
of LY3002813 and the IV administration of LY3002813 in combination with the oral 
administration of LY3202626 to the intended study population according to the proposed clinical 
investigation plan and also provide a sufficient margin of safety for the proposed design and 
doses.  There are currently no disease-modifying treatments for AD.  The potential benefits of 
LY3002813 and LY3002813 in combination with LY3202626 showing disease-modifying 
properties in AD are considered to outweigh the potential risks.
More information about the known and expected benefits, risks, SAEs and reasonably 
anticipated AEs of LY3002813 and LY3202626 are to be found in the respective IB(s).
4.
Objectives and Endpoints
Table AACG.4.1.
Objectives and Endpoints
Primary Objective
Primary Endpoint
To test the hypothesis that LY3002813 alone 
and/or in combination with LY3202626
administered for up to 7276 weeks will decrease 
the cognitive and/or functional decline in 
patients with early symptomatic AD
Change in cognition and function as measured by the 
change in integrated Alzheimer’s Disease Rating Scale 
(iADRS) score from baseline to 18 months
Secondary Objectives
Secondary Endpoints
To assess the effect of LY3002813 alone and in 
combination with LY3202626 vs. placebos on 
clinical progression in patients with early 
symptomatic AD
Change in cognition from baseline to 18 months as 
measured by:

the change in Alzheimer’s Disease Assessment 
Scale—Cognitive subscale (ADAS-Cog13) 
score

the change in Clinical Dementia Rating Scale 
Sum of Boxes (CDR-SB) score

the change in Mini Mental State Examination 
(MMSE) score

the change in Alzheimer’s Disease Cooperative 
Study-instrumental Activities of Daily Living 
scale (ADCS-iADL) score 

I5T-MC-AACG(d) Clinical Protocol
Page 136
LY3002813
To assess the effect of LY3002813 alone and in 
combination with LY3202626 vs. placebo on 
brain amyloid deposition
Change in brain amyloid plaque deposition from 
baseline through 18 months as measured by florbetapir
F18 PET scan  
To assess the effect of LY3002813 alone and in 
combination with LY3202626 vs. placebo on 
brain tau deposition
Change in brain tau deposition from baseline to 18 
months as measured by flortaucipir F18 PET scan  
To assess the effect of LY3002813 alone and in 
combination with LY3202626 vs. placebo on 
brain volume measures
Change in volumetric MRI measures from baseline to 
18 months.
To assess the effect of combination therapy with 
LY3002813 and LY3202626 vs LY3002813 
alone on clinical progression in patients with 
early symptomatic AD
Change from baseline to 18 months in iADRS score, 
ADAS-Cog13 score, CDR-SB score, MMSE score, 
ADCS-iADL score
Safety Objective
Safety Endpoints
To evaluate safety and tolerability of 
LY3002813 alone and in combination with 
LY3202626

Standard safety assessments:
o
spontaneously reported adverse events 
(AEs)
o
clinical laboratory tests
o
vital sign and body weight 
measurements
o
12-lead electrocardiograms (ECGs)
o
physical and neurological 
examinations

MRI (ARIA and emergent radiological 
findings)

Skin examination

Eye examination

Columbia Suicide Severity Rating Scale
(C-SSRS)
Exploratory Objectives
Exploratory Endpoints
To assess the effect of LY3002813 alone and in 
combination with LY3202626 vs. placebos, as 
well as combination therapy with LY3002813 
and LY3202626 vs LY3002813 alone on 
clinical progression in patients with early 
symptomatic AD

the change in dependence level derived from 
ADCS-ADL scale scores
To assess peripheral PK and presence of 
anti-LY3002813 antibodies over 72in 
LY3002813 alone and in combination with 
LY3202626 over 76 weeks

Plasma pharmacokinetics of LY3002813

Anti-drug-antibodies (ADA) against 
LY3002813 including treatment-emergent 
ADA and neutralizing antibodies.
To assess peripheral PK of LY3202626  in 
combination with LY3002813 over 76 weeks

Plasma Pharmacokinetics of LY3202626 
To assess the effect of combination therapy with 
LY3002813 and LY3202626 vs LY3002813 
alone on brain amyloid deposition

Change in brain amyloid plaque deposition 
from baseline through 18 months as measured 
by florbetapir F18 PET scan  

I5T-MC-AACG(d) Clinical Protocol
Page 137
LY3002813
To assess the effect of combination therapy with 
LY3002813 and LY3202626 vs LY3002813 
alone on brain tau deposition

Change in brain tau deposition from baseline to 
18 months as measured by flortaucipir F18 
PET scan
5.
Study Design
5.1.
Overall Design
Study AACG is a multicenter, randomized, double-blind, placebo-controlled, Phase 2 study of 
LY3002813, alone and in combination with LY3202626, in subjects with early symptomatic AD.  
The 133124-week study includes a screening period of up to 9 weeks, a treatment period of up to 
7276 weeks with final evaluations occurring 4 weeks later at Week 76, and , a 484-week 
posttreatment follow-up, and a 44-week immunogenicity and safety follow-up period.  Subjects 
who meet entry criteria will be randomized in a 1:1:1 ratio to one of the following treatments:
•
LY3002813: monotherapy (LY3002813-M):  IV LY3002813 (700 mg Q4WK for the 
first 3 doses, then 1400 mg Q4WK) for in combination with daily oral placebo up to 7276 weeks,
•
LY3002813 in combination with LY3202626 (LY3002813-C):  IV LY3002813 (700 mg 
Q4WK for the first 3 doses, then 1400 mg Q4WK) in combination with daily oral LY3202626 
(12 mg) up to 76 weeks, or
•
Placebo:  IV placebo Q4WK in combination with daily oral placebo for up to 7276
weeks.
The primary hypothesis being tested is that LY3002813 administered alone, or in combination 
with LY3202626, for up to 7276 weeks will result in a significant slowing in 
cognitive/functional decline compared with placebo as measured by the change from baseline to 
the end of the double blind treatment period (Week 76) on the integrated Alzheimer’s Disease 
Rating Scale (iADRS), in subjects with early symptomatic AD (where early symptomatic AD 
refers to the combination of 2 stages:  prodromal AD [MCI -AD] and mild AD dementia; Alaka 
et al. 2015).
Under previous versions of this protocol, LY3002813 was administered in combination with 
LY3202626, an inhibitor of β site amyloid precursor protein cleaving enzyme (BACE)1.  
However, as of this amendment (d), the combination therapy and the oral placebo have been 
discontinued from the study.

I5T-MC-AACG(d) Clinical Protocol
Page 138
LY3002813
[Old figure:]

I5T-MC-AACG(d) Clinical Protocol
Page 139
LY3002813
[Updated figure:]
Figure AACG.5.1.
Illustration of study design for Clinical Protocol I5T-MC-AACG.
5.1.1.Screening Period (Visit 1)
Once the MMSE criteria are met, 63 days are allowed for completion of Visit 1 screening 
assessments, procedures, and evaluation of results from laboratory tests, ECGs, physical and 
neurological examination, ophthalmological and dermatological exams, flortaucipir F18 PET, 
MRI, and florbetapir F18 PET.  Even though florbetapir F18 PET imaging may be the last 
screening procedure of the study, it is expected that the centrally read florbetapir F18 PET results 
will be available within the timeframe of 63 days.  However, it will not be a protocol 
deviationviolation should the screening florbetapir F18 PET results not be available until after 
63 days.
Patients whose screening florbetapir F18 PET results are not available until after 63 days will 
remain eligible within Visit 1 until these results become available.  Note:  If a patient’s screening 
florbetapir F18 PET results confirming evidence of amyloid burden are received by the site after 
63 days, laboratory tests (blood hematology, chemistry, and serum human chorionic 
gonadotropin [HCG] for females of childbearing potential) are to be repeated for that patient.  
Results of the repeated labs are to be reviewed by the investigator or qualified designee for 
assessment of the patient’s continued eligibility.  Repeat screening for MMSE, CBB, C-SSRS, 

I5T-MC-AACG(d) Clinical Protocol
Page 140
LY3002813
ECG, ophthalmological and dermatological exams, flortaucipir F18 PET imaging, and MRI, and 
laboratory testing for hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) RNA 
polymerase chain reaction (PCR), is not required.
Patients in active screening prior to implementation of amendment (d) remain eligible within 
Visit 1 until all screening procedures are completed and results are available. This will not be a 
protocol deviation.  Patients who complete Visit 1 beyond 63 days are to repeat laboratory tests 
(blood hematology, chemistry, and serum HCG for females of childbearing potential) prior to 
being randomized.  The results of these laboratory tests are to be reviewed by the investigator or 
qualified designee for assessment of the patient’s continued eligibility.  Repeat screening for 
MMSE, CBB, C-SSRS, ECG, flortaucipir F18 PET imaging, MRI, and laboratory testing for 
HBsAg and HCV RNA PCR is not required.
5.1.1.1.
Screening Procedures
Screening entry and administrative procedures, cognitive assessments, safety assessments, (with 
the exception of ophthalmological and dermatological exams), and laboratory assessments (see 
Schedule of Activities in Section 2) are to be done at Visit 1 before the screening flortaucipir F18 
PET scan, MRI, and florbetapir F18 PET scan procedures.
5.1.1.1.1.
Modified Hachinski Ischemic Scale (MHIS)
Patients who score ≥4 are more likely to have a dementia of vascular etiology and are excluded 
from participating in the trial.
5.1.1.1.2.
Mini-Mental State Examination (MMSE)
The MMSE is a brief instrument used to assess cognitive function in elderly patients (Folstein et 
al.
5.1.1.1.5.
Screening Ophthalmological and Dermatological Examinations
[Section deleted]
5.1.1.1.6.5.1.1.1.5. Screening Positron Emission Tomography and Magnetic 
Resonance Imaging
With the exception of ophthalmological and dermatological exams, aAll other screening criteria 
should be met in order for the patient to proceed with flortaucipir F18 PET scan, followed by 
MRI, and a florbetapir F18 PET scan procedure.
5.1.1.1.6.2.5.1.1.1.5.2.
Screening MRI
A local screening MRI will be performed at Visit 1 as part of the study eligibility criteria.  With 
the exception of the evidence of amyloid pathology by florbetapir F18 PET scan, and 
ophthalmological and dermatological exams, a patient should meet all other Visit 1 eligibility 
criteria before having an MRI.  
5.1.1.1.6.3.5.1.1.1.5.3.
Screening Florbetapir F18 PET Scan

I5T-MC-AACG(d) Clinical Protocol
Page 141
LY3002813
With the exception of the MRI and ophthalmological and dermatological exams, a patient should 
meet all other Visit 1 eligibility criteria before having a screening florbetapir F18 PET scan. 
5.1.2. Double-Blind Period (Visit 2 through Visit 2122)
Patients who meet entry criteria will be enrolled and randomized to receive up to 7276 weeks of 
treatment with LY3002813-M, LY3002813-C, or placebo.
Patients are to take oral study medication (oral placebo or LY3202626) once per day in the 
morning.  The first dose should be taken the morning after the first dispensing of oral study 
medication at Visit 2.
A final Final endpoint measures and safety assessments visit for the double-blind period will be 
performed at Visit 2122 (Week 7680) 4 weeks following the patient’s last dose of study 
medication.  
5.1.3. Immunogenicity and Safety Follow-up Visits (Visits 801 through 804)
Patients are to return to the site for an immunogenicity and safety follow-up visits (Visit 801 
through Visit 804) beginning at Week 88 (or 12 weeks after their last dose of LY3002813 for 
collection of blood samples for anti-drug antibody [(ADA; anti-LY3002813 antibody]) and PK 
measurement, and assessment of adverse events, C-SSRS, and concomitant medications, and 
vital signs.
5.2.
Number of Participants
Approximately 266375 participants will be randomized.
5.4.
Scientific Rationale for Study Design
Continuing Standard of Care. During the double-blind treatment period (V2 to V21V22), 
changes in doses of available symptomatic medications for MCI or AD will require reporting to 
the sponsor and these changes should occur only when necessary for the adequate overall care of 
the patient. The effect of LY3002813 treatment alone or in combination with LY3202626 plus 
SOC will be compared with placebo plus SOC.
Dosing. As described more fully in Section 7.1, LY3002813 (700 mg or 1400 mg) will be 
administered every 4 weeks as an IV infusion of approximately 140 mL over a minimum of 30 
minutes and LY3202626 (12 mg) will be administered orally once a day.
Design. Study AACG is a multicenter, randomized, double-blind, placebo-controlled study of 
LY3002813, alone and in combination with LY3202626, in patients with early symptomatic AD 
(where early symptomatic AD refers to the combination of 2 stages:  prodromal AD [MCI AD] 
and mild AD dementia) (Alaka et al. 2015).  The study is intended to characterize the benefits 
and risks of treatment with LY3002813 alone or in combination with LY3202626 versus placebo 
in patients early symptomatic AD.
.... The use of a placebo comparator in Study AACG is needed to determine efficacy and safety 
of LY3002813 monotherapy and LY3002813 combination therapy.

I5T-MC-AACG(d) Clinical Protocol
Page 142
LY3002813
The duration of the double-blind period of the study is 7680 weeks and includes up to 7276
weeks of treatment, with endpoint measures and safety assessments at the end of the double-
blind treatment period (Week 76), to assess the safety, tolerability and efficacy of LY3002813 
alone or in combination with LY3202626 versus placebo, as well as LY3002813 alone versus 
LY3002813 in combination with LY3202626, and safety assessments at 80 weeks.
In addition to AE reporting, safety measures such as laboratory assessments, immunogenicity 
testing, vital signs and weight monitoring, ECG monitoring, physical examinations, neurological 
examinations dermatological examinations, ophthalmological examinations, MRI assessments, 
and assessments of suicidal ideation and behavior are included to facilitate a comprehensive 
safety evaluation.  For patients enrolled under previous versions of this protocol, which included 
a combination arm of LY3002813 (N3pG) and LY3202626 (BACE inhibitor-IV), final 
dermatological examinations by a dermatologist and final comprehensive ophthalmological
examinations by an ophthalmologist or optometrist (where permitted by law) will be performed 
at the next visit occurring after the patient stopped receiving LY3202626/oral placebo.
5.5.
Justification for Dose
....
The LY3202626 dose of 12 mg administered orally once a day was selected based on current 
nonclinical pharmacology and toxicology data and clinical PK, PD and safety data.  Doses of 
LY3202626 chosen for this study were based on central and peripheral PK/PD data from healthy 
subjects collected in a previous single- and multiple-dose study that were used to estimate the 
exposures necessary to achieve the desired levels of CSF Aβ reduction.  These exposure targets 
were then used to select a daily dose of 12 mg LY3202626 for this study.  This dose is less than 
the highest doses previously evaluated in healthy subjects (45 mg as a single dose, or 26 mg once 
a day for 14 days), which were found to be well tolerated.  As described in Section 3.2.4, 
LY3202626 appears to be well tolerated in an ongoing Phase 2 study investigating the effect of 3 
mg and 12 mg LY3202626.  Together, these data suggest that a dose of 12 mg LY3202626 will 
be well tolerated in an AD population and will allow evaluation of near maximal inhibition of Aβ 
production.
6.
Study Population
6.1.
Inclusion Criteria
....
Patient/Subject Characteristics
[4]
....  
A second study partner may serve as backup.  The study partner(s) is/are required to 
accompany the patient for signing consent.  One study partner is requested to be present 
on all days the Columbia Suicide Severity Rating Scale (C-SSRS)/Self-Harm Supplement 
Form is administered and must be present on all days theand cognitive and functional 
scales are administered (i.e., Visits 1, 2, 5, 8, 11, 15, 18, and 21/ED).  If a patient has a 

I5T-MC-AACG(d) Clinical Protocol
Page 143
LY3002813
second study partner, it is preferred that one study partner be primarily responsible for the 
CDR and ADCS-ADL assessments.  If a study partner(s) is not able to accompany the 
patient in person for visits other than those listed above, they must be available by 
telephone for the following assessments:
•
AEs and concomitant medications
•
relevant portions of the C-SSRS/Self-Harm Supplement Forms
•
CDR and ADCS-ADL (primary study partner if possible)
6.2.
Exclusion Criteria
Medical Conditions
[11]
Current serious or unstable illnesses including retinal, cardiovascular, hepatic, renal, 
gastroenterologic, respiratory, endocrinologic, neurologic (other than AD), psychiatric, 
immunologic, or hematologic disease and other conditions that, in the investigator’s 
opinion, could interfere with the analyses in this study; or has a life expectancy of 
<24 months.
[57]
[Note:  Criterion #57 has been deleted.] Ocular pathology that significantly limits ability 
to reliably evaluate vision or the retina, or puts participant at undue risk for vision loss 
during the study.
[18]
[Note:  Criterion #18 has been deleted.] History of vitiligo and/or current evidence of 
post-inflammatory hypopigmentation.
Magnetic Resonance Imaging, Vital Signs, Electrocardiograms, Laboratory Tests, and 
Physical Examination
[54]
Patients with past history of Hepatitis C should have hepatitis C virus (HCV) ribonucleic 
acid (RNA) polymerase chain reaction (PCR) testing at screening and are excluded if 
HCV RNA PCR is positive.
Prior/Concomitant Therapy
[32]
[Note:  Criterion #32 has been deleted.] Current use of strong inducers of CYP3A (see 
the Manual of Operations for a list of excluded drugs).
[37]
[Note: Criterion #37 has been deleted.] Have known allergies to LY3202626, related 
compounds, or any components of the formulation.
Prior/Concurrent Clinical Trial Experience
[47]
[Note: Criterion #47 has been replaced by criteriona #55 and #56.]
[56]
[Note: Criterion #56 has been deleted.] Have previously had LY3202626 treatment 
discontinued due to treatment-related adverse event.
6.2.1.Rationale for Exclusion of Certain Study Candidates

I5T-MC-AACG(d) Clinical Protocol
Page 144
LY3002813
The use of LY3002813 and LY3202626 in older patients is anticipated; thus this study will 
specifically examine the efficacy and safety in an elderly population.  Criterion [2] defines the 
population age range for the purposes of this study.  Therefore, patients not meeting the age 
criterion are excluded.
6.3.
Lifestyle Restrictions
2.
Patients should avoid use of tanning beds and self-tanning products.
3.
Patients should wear a hat and appropriate clothing when exposed to sunlight; use a 
sunscreen with a skin protection factor (SPF) of at least 15; and protect their lips with a 
lip balm containing sunblock.
7.
Treatments
7.1.
Treatments Administered
This study involves a comparison of LY3002813 administered as an IV infusion of 
approximately 140 mL over a minimum of 30 minutes compared with LY3002813 in 
combination with LY3202626 administered orally once a day, and placebo.  In the double-blind 
period, the treatment groups will be given either an IV infusion of LY3002813 monotherapy 
(LY3002813-M), LY3002813 combination therapy (LY3002813-C), or Placebo for up to 7276
weeks.
....
The LY3202626 dose will remain 12 mg throughout the double-blind treatment period.  Table 
AACG.7.1 shows the 23 treatment regimens during the double-blind period.
Table AACG.7.1.
Treatment Regimens, Double-Blind Period
Regimen
Dose
Visit 2 (Week 0) through Visit 21 (Week 76)
LY3002813-M
LY3002813 (700 mg intravenous infusion every 4 weeks x 3 doses, then 1400 mg 
intravenous infusion every 4 weeks for up to 72 weeks) in combination with 
orally dosed placebo tablet once per day in the morning x 76 weeks
LY3002813-C
LY3002813 (700 mg intravenous infusion every 4 weeks x 3 doses, then 1400 mg 
intravenous infusion every 4 weeks for up to 72 weeks) in combination with 
LY3202626 (12 mg tablet orally once a day in the morning for 76 weeks)
Placebo
Intravenously dosed placebo infusion every 4 weeks for up to 72 weeks in 
combination with orally dosed placebo tablet once per day in the morning x 76 
weeks
Abbreviations:  C = combination therapy; M = monotherapy.

I5T-MC-AACG(d) Clinical Protocol
Page 145
LY3002813
7.1.1.2.
LY3202626 Packaging and Labelling
LY3202626 will be supplied as 12-mg tablets.  The study drug and placebo will be identical in 
appearance and will be packaged in blister packs.
7.2.
Method of Treatment Assignment
Patients will be randomized to LY3002813-M, LY3002813-C, or Placebo in a 1:1:1 ratio.
7.2.1.Selection and Timing of Doses
Assessment of LY3002813 and LY3202626 safety and tolerability is a central objective; 
therefore, monitoring 100 patients on LY3002813-M over 7276 weeks in parallel with 
approximately 100 patients on LY3002813-C over 76 weeks of exposure provides data to assess 
safety for further clinical development.
The actual time of both LY3002813 and LY3202626 dose administrations on the day of study 
visits will be recorded in the subject’s case report form (CRF).  In addition, the actual time of 
LY3202626 dose administration for the 2 days prior to each visit at which LY3202626 PK 
samples will be collected will be recorded in the subject’s CRF.
7.2.1.1.
LY3002813:  Selection and Timing of Doses
.... Intravenous study medication given at a dosing interval of less than 21 days at any time 
during the study will be considered a protocol deviationviolation.  
7.2.1.2.
LY3202626:  Selection and Timing of Doses
[Section deleted]
7.3.
Blinding
This is a double-blind study, with design to maintain blinding to treatmentboth LY3002813 and 
LY3202626 treatments.  
7.4.
Dosage Modification
7.4.1.LY3002813 Dosage Modification for ARIA-E
7.4.1.1.
LY3002813 Dosage Modification for ARIA-E
Patients will continue LY3202626 at 12 mg per day.
7.4.1.2.
7.4.2 LY3002813 Dosage Modification for ARIA-H
Patients will continue LY3202626 at 12 mg per day.
Patients permanently discontinued from LY3002813 are to continue taking LY3202626 unless 
they are permanently discontinued from LY3202626 treatment or from the trial.
7.4.2.LY3202626 Dosage Modification

I5T-MC-AACG(d) Clinical Protocol
Page 146
LY3002813
[Section deleted]
7.6.2.LY3202626 Treatment Compliance
[Section deleted]
7.7.
Concomitant Therapy
Allowed Medications.  Use of approved or standard of care treatments for AD is permitted during 
the study, provided that such medications dose has been unchanged for 2 months before Visit 2.  
Doses of these medications should remain constant throughout the double-blind period (Visit 2 
to Visit 2122).
Prior to V21V22, before a patient starts, stops, or changes doses of AChEIs and/or memantine 
or other treatments for their AD, the Sponsor or designee must be contacted to determine 
whether or not the patient should continue in the study and whether or not clinical outcome 
measures should be performed.  Failure to notify Lilly or its designee regarding starting, 
stopping or changing doses of AChEIs and/or memantine or other treatments for their AD 
prior to V21V22 will be considered a protocol deviationviolation.
If unforeseen starting, stopping, or changing of stable doses of drugs affecting CNS function 
occurs prior to V21V22 of the study, Lilly or its designee must be contacted to determine 
whether or not the patient should continue in the study and whether or not outcome measures 
should be performed.  Failure to notify Lilly or its designee regarding starting, stopping or 
changing doses of CNS medications prior to V21V22 of the study will be considered a protocol 
deviationviolation.
Excluded Medications.
Concomitant therapies that are prohibited during treatment with LY3002813:  IgG therapy 
(also known as gamma globulin or intravenous immunoglobulin [IVIG]) is not allowed during 
the study.
Concomitant therapies that are prohibited during treatment with LY3202626:

Use of depigmenting agents, such as, hydroquinone

Current use of strong inducers of CYP3A (See the Manual of Operations for a list of 
excluded drugs)

Current use of drugs known to significantly prolong the QT interval (See the Manual of 
Operations for a list of excluded drugs)

Use of any drug of abuse, including but not limited to cannabis, illicit amphetamine, 
cocaine, illicit opiates, propoxyphene, methadone, methaqualone, phencyclidine, or illicit 
barbiturate
7.8.
Treatment after the End of the Study
7.8.1.Treatment after Study Completion

I5T-MC-AACG(d) Clinical Protocol
Page 147
LY3002813
There is no planned open label extension at this time, or plan to otherwise make LY3002813 or 
LY3202626 available to patients after conclusion of the study.
8.
Discontinuation Criteria
8.1.
Discontinuation from Study Treatment
•
Treatment with LY3002813 will also be permanently discontinued in patients with:
o
Adverse event or clinically significant laboratory value, ECG result, physical 
examination finding, (including eye or skin examination), MRI finding (such as 
symptomatic ischemic stroke), C -SSRS result, or vital sign measurement of such 
severity that, in the opinion of the investigator or Lilly-designated medical monitor, 
continued treatment is not in the best interest of the patient.
Patients permanently discontinued from one treatment may continue to receive the other 
treatment and continue in the trial.  Patients may also permanently discontinue study 
treatmentboth treatments and remain in the trial.
If LY3202626 oral dose is permanently discontinued but the patient remains in the study, a final 
sample should be collected, provided the last dose of LY3202626 is within 3 days of the visit.  
Dosing dates and times should be collected.  No other PK samples for LY3202626 are required 
after the final sample.
8.1.1.Temporary Discontinuation from Study Treatment
8.1.1.1.
Temporary Discontinuation from LY3002813 Study Treatment Due to 
ARIA-E
8.1.1.1.1.
Temporary Discontinuation from LY3002813 Study Treatment Due to ARIA-E
8.1.1.2.
Temporary Discontinuation from LY3202626 Study Treatment
[Section deleted]
8.2.
Discontinuation from the Study
Subjects discontinuing from the study prematurely for any reason must complete AE and other 
safety follow-up per Section 2 (Schedule of Activities), Section 9.2 (Adverse Events), and 
Section 9.4 (Safety) of this protocol.  In addition, subjects discontinuing from the study 
prematurely should be encouraged to return to the site beginning 12 weeks after their ED visit for 
an immunogenicity and safety assessments (Visitsassessment visit (Visit 801 through 804, as 
described in Section 5.1.3).
9.
Study Assessments and Procedures
9.1.
Efficacy Assessments
Note that the ADAS-Cog and MMSE should must be administered by a different rater than the 
ADCS-ADL and CDR.  

I5T-MC-AACG(d) Clinical Protocol
Page 148
LY3002813
9.1.2.Secondary Efficacy Assessments
9.1.2.4.
Mini-Mental State Examination (MMSE)
The MMSE is a brief instrument used to assess cognitive function in elderly patients (Folstein et 
al. 1975).
9.1.3.Biomarker Efficacy Measures (Double-Blind Period)
Florbetapir F18 PET scan. Change in amyloid burden (as assessed by florbetapir F18 PET 
signal) will be compared in LY3002813-, LY3002813/LY3202626- and placebo-treated patients 
for those patients who undergo florbetapir F18 PET scans at baseline, Week 52 [Visit 15], and 
Week 76 [Visit 21] or early discontinuation [ED]) as described in the Schedule of Activities 
(Section 2).
Flortaucipir F18 PET scan.  Change in tau burden (as assessed by flortaucipir F18 PET signal) 
will be compared in LY3002813-, LY3002813/LY3202626- and placebo-treated patients for 
those patients who undergo both baseline and endpoint (Visit 21 [Week 76] or ED) flortaucipir 
F18 scans as described in the Schedule of Activities (Section 2).
Volumetric MRI.  Magnetic resonance imaging of the brain will be performed according to the 
Schedule of Activities (Section 2).  LY3002813-, LY3002813/LY3202626- and placebo-
treatment effects on volumetric MRI will be assessed and compared to evaluate the loss of brain 
volume that occurs in AD patients.
9.2.1.2.
Adverse Events of Special Interest
Specific safety topics of interest for this study include, but are not limited to, the following:
•
QT prolongation
•
Adverse eye effects
•
Adverse skin effects including rash and hypopigmentation
•
Liver toxicity
9.3.
Treatment of Overdose
9.3.1.Treatment of LY3002813 Overdose
There is no known antidote to LY3002813.  In case of overdose, use appropriate monitoring and 
supportive therapy.
9.3.2.Treatment of LY3202626 Overdose
There is no known antidote to LY3202626.  In the case of known or suspected overdose, 
monitoring of cardiac, hepatic, and hematological effects is essential, and appropriate supportive 
therapy should be initiated, as appropriate.  Refer to the LY3202626 IB.
9.4.
Safety

I5T-MC-AACG(d) Clinical Protocol
Page 149
LY3002813
9.4.1 Physical and Neurological Examinations
Complete physical examinations will be performed at screening, baseline, and Weeks 12, 24, 52, 
76, 80, and ED as indicated in the Schedule of Activities (Section 2).  
9.4.6 Other Tests
9.4.6.3.
Ophthalmological Examination
While the BACE inhibitor LY3202626 is no longer being administered in this study (see Section 
5.1), ophthalmological examinations in patients who previously received LY3202626 or oral 
placebo will be performed at the next scheduled examination time point after their final dose of 
oral study medication (see the Schedule of Activities [Section 2]).  Patients who received 
LY3202626/oral placebo after their Visit 9 ophthalmological examination are to have an 
unscheduled ophthalmological examination at the next available opportunity.  Patients screened 
or randomized under the current amendment are not required to undergo any ophthalmological
examinations at baseline or any other study visits.
All Patients who previously received LY3202626 or oral placebo will undergo comprehensive 
ophthalmological examinations performed by an ophthalmologist or optometrist (where 
permitted by law) to assess visual function and morphology.  Scheduled examinations will 
include the following:  visual acuity, intraocular pressure, dilated funduscopic exam (dilation 
only performed in patients without contraindication to mydriatics), slit lamp exam, color 
photography of the retina, and optical coherence tomography (OCT) or equivalent; examinations 
will also include color vision assessment.  Assessments will preferably be performed at times 
shown in the Schedule of Activities (Section 2), preferably by the same ophthalmologist or 
optometrist for each patient’s visit.  Patients who complain of vision disturbance, such as change 
in field of vision, color, acuity or anything potentially localizable to the retina, during the clinical 
trial should be referred to the ophthalmologist or optometrist (where permitted by law) for 
unscheduled evaluation.
Data from the eye ophthalmological examination visits will be provided from the local 
ophthalmologist or optometrist to the investigator.  Based on the morphological and functional 
results, the investigator will include or exclude the patient in consultation with the performing 
eye examiner,.    
The local ophthalmologist or optometrist will review the color photography and OCT to aid in 
the investigator’s assessment of study eligibility and for immediate patient management.  
Additionally, the color photography of retina and OCT will be analyzed by a central reader.
9.4.6.4.
Dermatological Examination
While the BACE inhibitor LY3202626 is no longer being administered in this study, A complete 
dermatological examinations in patients who previously received LY3202626 or oral placebo 
will skin examination will be performed at the next scheduled examination time point after their 
final dose of oral study medication (see times shown in the Schedule of Activities ([Section 2]).  
Patients who received LY3202626/oral placebo after their Visit 8 dermatological examination 

I5T-MC-AACG(d) Clinical Protocol
Page 150
LY3002813
are to have an unscheduled dermatological examination at the next available opportunity.  
Patients screened or randomized under the current amendment are not required to undergo any 
skin exams at baseline or any other study visits.
This examination will ), preferably be performed by the same dermatologist for each patient’s 
visit.  All skin dermatological examinations must be performed by a dermatologist who will 
inspect the patient’s unclothed full body using an ultraviolet (UV) light.  The initial examination 
will include Fitzpatrick skin-type classification scale.
9.4.7.Safety Monitoring
The Lilly clinical research physician or scientist will, as appropriate, consult with the 
functionally independent Global Patient Safety therapeutic area physician or clinical scientist, 
and periodically review:
•
AEs including monitoring of hypersensitivity and infusion reactions, AEs associated with 
anti-LY3002813 antibodies (immunogenicity), ARIA-H, ARIA-E-E, eye and skin, ECG 
findings, neurological findings, hemorrhagic stroke, microhemorrhage (cerebral 
microhemorrhage, cerebellar microhemorrhage, brain stem microhemorrhage) as identified 
by investigator, and suicide-related thoughts and behaviors.
9.4.7.1.2.
Management of Infusion Reactions
Additional data should also be collected via the CRF/electronic data entry. Pplease see the 
Operations Manual for more detail.
9.4.7.2.
LY3002813 Immunogenicity
In order to preserve the blind, patients will need to complete Visits 801 throughto 804 until all 
patients in the trial have reached Visit 2122 and datalock for the treatment period has been 
achieved.
In the event of a finding of hypersensitivity, the investigator is to complete the CRF regarding 
the presence or absence of symptoms related to the hypersensitivity.
9.4.7.4.
Amyloid-Related Imaging Abnormalities (ARIA-E and ARIA-H)
In the event of a finding of ARIA E on MRI, the investigator is to complete the CRF regarding 
the presence or absence of symptoms related to the ARIA-E.  
If the above mentioned symptoms are reported, and ARIA E is suspected, then the abnormality is 
best detected by fluid attenuation inversion recovery (FLAIR) sequences on magnetic resonance 
imaging (MRI) and ARIA H is best detected with the T2* gradient recalled echo on MRI.
9.4.8.Appropriateness of Safety Assessments
The clinical safety measurements (AE reporting, physical examinations, neurological 
examinations, ophthalmological examinations, dermatological examinations, vital signs, ECGs, 
and clinical safety laboratory tests [including immunogenicity]; Section 9.2 and Section 9.4) are 

I5T-MC-AACG(d) Clinical Protocol
Page 151
LY3002813
well-established methods in drug development research and are standard procedures for clinical 
trials.
Performance of ophthalmological and dermatological examinations isare indicated in subjects 
who were previously treated with LY3202626, based on the potential for the occurrence of 
adverse retinal effects and hypopigmentation, respectively, during treatment with LY3202626.  
While LY3202626 is no longer being administered in this study, dermatological and 
ophthalmological examinations in subjects who previously received this therapy or oral placebo 
will be performed at the next scheduled examination time point after their final dose of oral study 
medication, in accordance with the Schedule of Activities (Section 2).  Patients who received 
LY3202626/oral placebo after their Visit 8 or 9 dermatological or ophthalmological examination 
are to have an unscheduled examination at the next available opportunity.  Patients screened or 
randomized under the current amendment are not required to undergo any dermatological or 
ophthalmological examinations at baseline or any other study visits.
9.5.
Pharmacokinetics
At the visits and times specified in the Schedule of Activities (Section 2), venous blood samples 
of approximately 4 mL each will be collected to determine the serum concentrations of 
LY3002813 and venous blood samples of approximately 2 mL each will be collected to 
determine plasma concentrations of LY3202626.  Instructions for the collection and handling of 
blood samples will be provided by the sponsor.  The actual date and time (24-hour clock time) of 
each sampling will be recorded.
If LY3202626 oral dose is permanently discontinued but the patient remains in the study, a final 
sample should be collected, provided the last dose of LY3202626 is within 3 days of the visit.  
Dosing dates and times should be collected.  No other PK samples for LY3202626 are required 
after the final sample.
9.7.
Pharmacogenomics [OR] Genetics
9.7.1.Apolipoprotein E Genotyping
Blood sampling for APOE genotyping will be performed as shown in the in the Schedule of 
Activities (Section 2).  
10.
Statistical Considerations
10.1. Sample Size Determination
Approximately 250375 subjects will be enrolled and randomized in a 1:1:1 ratio to the 2three
treatment arms (placebo, LY3002813-M, and LY3002813-C).  It is expected that approximately 
200300 subjects will complete the double-blind treatment period of the study (approximately 100 
per treatment arm).  This sample size will provide approximately 8486% power to demonstrate 
that theat least one active treatment arm has a ≥ 0.6 posterior probability of slowing down 
iADRS progression over placebo by at least 3 points.  The assumption for power calculation is 
that mean progression levels in the placebo, LY3002813-M and LY3002813-C arms are 
approximately 12, 8 (33% slowing), and 6 points (50% slowing) over 18 months, respectively, 

I5T-MC-AACG(d) Clinical Protocol
Page 152
LY3002813
with common standard deviation of 17.  If theboth active treatment arm isarms are placebo-like 
with no efficacy, the probability of passing the efficacy criterion specified above (i.e., false 
positive) is approximately 611%.  The simulation for the power calculation and sample size 
determination was carried out in FACTS Version 6.05.5.
10.2. Populations for Analyses
For purposes of analysis, in general the following populations are defined unless otherwise 
specified:
For efficacy analysis, the Full Analysis Set will group patients according to randomized 
treatment assignment (LY3002813 or placebo), even if the patient does not take the assigned 
treatment, does not receive the correct treatment, or otherwise does not follow the protocol.  
When change from baseline is assessed, patients will be included in the analysis only if both a 
baseline and at least 1 valid post-baseline measure are available.
For safety analysis, all patients who received at least 1 dose of randomized study treatment 
(LY3002813, LY3202626 or placebo) will be included in the safety analysis set.  In safety data 
presentations, erroneously treated patients (e.g., those randomized to “Treatment A” but actually
given “Treatment B”) will be accounted for in their actual treatment groups.
There were approximately 48 patients randomized before the removal of LY3202626 treatment 
in protocol amendment (d) (about 16 each in the LY3002813 and LY3202626 combination 
therapy arm, LY3002813 monotherapy arm, and placebo arm). Patients already randomized to 
the former LY3002813 monotherapy arm and placebo arm will be pooled with patients 
randomized after protocol amendment (d) to form the Full Analysis Set and safety analysis set 
specified above.  Data from patients randomized to the LY3002813 and LY3202626 
combination therapy arm will be summarized separately and will not be included in treatment 
comparisons on efficacy and safety endpoints. The total number of patients to be randomized in 
the study is approximately 266.
10.3.2.
Treatment Group Comparability
10.3.2.2.
Subject Characteristics
The patient’s age, gender, race, height, body weight, BMI (weight (kg) / [height (m)]2), tobacco 
use, alcohol use, caffeine use, years of education, work status, time since onset of first AD 
symptoms, time since diagnosis, baseline MMSE, CBB score at Visit 1, apolipoprotein E 
(APOE) genotype (E4 carrier vs. non-carrier), having 1 or more first degree relatives with AD, 
and AChEI and/or memantine use at baseline will be recorded.
10.3.3.
Efficacy Analyses
10.3.3.1.
Primary Analyses
The primary objective of this study is to test the hypothesis that IV infusion of LY3002813 alone 
or in combination with LY3202626  will slow the cognitive and/or functional decline of AD as 

I5T-MC-AACG(d) Clinical Protocol
Page 153
LY3002813
measured by the composite measure iADRS compared with placebo in patients with early 
symptomatic AD.  This will be assessed using an MMRM analysis.
The primary time point for treatment comparison will be at Week 76.  The treatment group 
contrast in least-squares mean progression and its associated p-value and 95% CI will be 
calculated for the treatment comparisons of LY3002813-M vs. placebo and LY3002813-C vs.   
placebo, using the MMRM model specified above.  In addition, Bayesian posterior probability of 
the active treatment arm being superior to placebo by at least a margin of interest (25% slowing 
of placebo progression) will also be calculated assuming a non-informative prior.
10.3.4.
Safety Analyses
10.3.4.5.
ARIA-E and ARIA-H
The incidence of ARIA-E will be summarized.  Change in ARIA-E status from baseline, to each 
subsequent MRI (in the event of unscheduled MRIs), and to double-blind period endpoint (Visit 
2122) will be compared between treatment groups using Fisher’s exact test.
10.3.5.
Pharmacokinetic/Pharmacodynamic Analyses
Compartmental modeling of LY3002813 and LY3202626 PK data using nonlinear mixed effects 
modeling or other appropriate software may be explored, and population estimates for clearance 
and central volume of distribution may be reported.  Depending on the model selected, other PK 
parameters may also be reported.  Exploratory graphical analyses of the effect of dose level or 
demographic factors on PK parameters may be conducted.  If appropriate, data from other 
studies of LY3002813 or LY3202626 may in be used in this analysis.
Concentrations of LY3202626 were collected under the original version of this protocol, as well 
as amendments (a-c).  These data will be summarized in the final study report and may be 
analyzed graphically.  If appropriate, exploratory analyses may be conducted to evaluate 
potential relationships between LY3202626 concentrations and LY3002813 concentration.
The PK/PD relationships between plasma LY3002813 concentration and SUVr, cognitive 
endpoints, ARIA incidence rate or other markers of PD activity may be explored graphically.  
The relationship between the presence of antibodies to LY3002813 and PK, PD, safety and/or 
efficacy may be assessed graphically.  The effect of LY3202626 exposure on SUVr, cognitive 
endpoints, or other markers of PD activity may also be explored graphically.  Graphical and/or 
descriptive analyses may be explored to evaluate potential interactions between LY3002813 and 
LY3202626 for PK.  If warranted, additional analysis may be explored to evaluate potential 
interactions for ADA, PD and other endpoints (PET scan, ARIA-E, etc.).
10.3.6.
Interim Analyses
There will be periodical safety data reviews during the study and the external DMC is authorized 
to evaluate results from unblinded safety data reviews.  

I5T-MC-AACG(d) Clinical Protocol
Page 154
LY3002813
11.
References
DeMattos R, May P, Racke M, Hole J, Tzaferis J, Liu F, DeLong C, Day T, Yang Z, Boggs L, 
Monk S, Mergott D, Tang Y, Lu J, Hutton M, Nordstedt C, Anderson W, Iverson P. 
Combination therapy with a plaque-specific abeta antibody and bace inhibitor results in dramatic 
plaque lowering in aged pdapp transgenic mice. Alzheimer’s Dement. 2016;12(7):P149.
Doody RS, Raman R, Farlow M, Iwatsubo T, Vellas B, Joffe S, Kieburtz K, He F, Sun X, 
Thomas RG, Aisen PS; Alzheimer’s Disease Cooperative Study Steering Committee, Siemers E, 
Sethuraman G, Mohs R; Semagacestat Study Group. A phase 3 trial of semagacestat for 
treatment of Alzheimer’s disease. N Engl J Med. 2013;369(4):341-350.
Fleisher AS, Lowe SL, Liu P, Shcherbinin S, Li L, Chua L, Nakano M, Hawdon A, Willis BA, 
Schwarz AJ, DeMattos RB, Mintun MA, Irizarry MC. Significant and sustained florbetapir F18 
uptake reduction in patients with symptomatic Alzheimer’s disease with LY3002813, a β 
amyloid plaque-specific antibody. Presented at the Alzheimer’s Association International 
Conference 2018, July 22, 2018, Chicago, IL.
Hendrix JA, Bateman RJ, Brashear HR, Duggan C, Carrillo MC, Bain LJ, DeMattos R, Katz RG, 
Ostrowitzki S, Siemers E, Sperling R, Vitolo OV. Challenges, solutions, and recommendations 
for Alzheimer’s disease combination therapy. Alzheimers Dement. 2016;12(5):623-630.
Hole JT, Racke MM, Tzaferis JA, Liu F, Oluoch H, Ahmed Z, Fisher A, Anderson W, Iversent 
P, Gonzales C, Yang Z, Boggs LN, Monk SA, Mergott DJ, Yang YYT, Lu J, Irizarry MC, Sims 
JR, May PC, Hutton M, Nordstedt C, DeMattos RB. Combination therapy with a plaque-specific 
abeta antibody and a bace inhibitor results in dramatic plaque reduction in a dose-dependent 
manner in aged pdapp transgenic mice. Alzheimers Dement. 2016;12(7):P-1191 (Abstract).
Jacobsen H, Ozmen L, Caruso A, Narquizian R, Hilpert H, Jacobsen B, Terwel D, Tanghe A, 
Bohrmann B. Combined treatment with a BACE inhibitor and anti-Aβ antibody gantenerumab 
enhances amyloid reduction in APP London mice. J Neurosci. 2014 27;34(35):11621-11630.
Selkoe DJ. Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and 
behavior. Behav Brain Res. 2008;192:106-13.
Turner PR, O’Connor K, Tate WP, Abraham WC. Roles of amyloid precursor protein and its 
fragments in regulating neural activity, plasticity and memory. Prog Neurobiol. 2003;70(1):1 32.
Appendix 5.
Flortaucipir F18 Tau PET Imaging
Inclusion Criteria for Flortaucipir F18 PET Scans
With the exception of the ophthalmological and dermatological examinations, MRI and 
florbetapir F18 PET scan, a patient should meet all other Visit 1 eligibility criteria before having 
a flortaucipir F18 PET scan.
PET Scan-Specific Information
PET Scan Procedures

I5T-MC-AACG(d) Clinical Protocol
Page 155
LY3002813
Scan Safety
The primary risk related to flortaucipir F18 PET is F18’s radiation exposure. 
....
•
flortaucipir F18 PET scans should to be performed at least 16 hours apart from the 
florbetapir F18 PET scans due to the half-life of fluorine 18.
With respect to other compound-related risks, flortaucipirAV-1451 was positive in the in vitro 
hERG assay.  
Nonperformance of postbaseline flortaucipir F18 PET scans in patients taking a medication 
known to prolong QT interval will not be considered a protocol deviationviolation.
Appendix 6.
Florbetapir F18 Amyloid PET Imaging
Inclusion Criteria for Florbetapir F18 PET Scans
With the exception of the MRI, ophthalmological and dermatological exams, a patient should 
meet all other Visit 1 eligibility criteria before having a florbetapir F18 PET scan.
PET Scan-Specific Information
PET Scan Procedures
PET Scan Safety
•
florbetapir F18 PET scans should to be performed at least 16 hours apart from the 18F
flortaucipir F18 PET scan due to the half-life of fluorine 18.

Leo Document ID = 29a7b9e3-12e0-407a-97a6-57f6cc8de831
Approver: 
Approval Date & Time: 09-Oct-2018 12:54:09 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 09-Oct-2018 13:11:13 GMT
Signature meaning: Approved
PPD
PPD