Proof of Concept of the Effect of Intravenous Immunoglobulin on Cerebral and Retinal Amyloid in Mild Cognitive Impairment Due to Alzheimer Disease
Phase: PHASE2
Conditions: Mild Cognitive Impairment
Sponsor: Sutter Health

Sutter Institute for Medical Research 
 
PI: Shawn Kile, MD 
Page 1                                                                                                                              v 9.22.17 
Proof of concept of the effect of Intravenous immunoglobulin on cerebral and retinal 
amyloid in mild cognitive impairment due to Alzheimer Disease 
 
 
 
SPONSOR: 
Sutter Institute for Medical Research 
PRINCIPAL INVESTIGATOR: 
Shawn Kile, MD  
SPONSOR PROTOCOL#: 
SIMR_Neuro17_SIMR_Kile_IVIG POC 
ORIGINAL VERSION DATE: 
September 13, 2017 
AMENDMENT 1 DATE: 
September 22, 2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CONFIDENTIAL 
 
The information contained in this document is regarded as confidential and, except to the extent 
necessary to obtain informed consent, may not be disclosed to another party unless law or regulations 
require such disclosure. Persons to whom the information is disclosed must be informed that the 

Sutter Institute for Medical Research 
 
PI: Shawn Kile, MD 
Page 2                                                                                                                              v 9.22.17 
information is confidential and may not be further disclosed. 
 
Proof of concept of the effect of Intravenous immunoglobulin on cerebral and retinal 
amyloid in mild cognitive impairment due to Alzheimer Disease 
1 
SCHEDULE OF STUDY ACTIVITIES ................................................................................. 4 
2 
BACKGROUND .................................................................................................................. 5 
3 
STUDY OBJECTIVES AND ENDPOINTS .......................................................................... 5 
3.1 
Primary Objective......................................................................................................... 5 
3.2 
Primary Endpoints........................................................................................................ 5 
4 
STUDY PLAN ..................................................................................................................... 5 
4.1 
Study design ................................................................................................................ 5 
4.2 
Subject population ....................................................................................................... 5 
4.3 
Estimated study duration.............................................................................................. 6 
5 
SUBJECT SELECTION ...................................................................................................... 6 
5.1 
Inclusion criteria ........................................................................................................... 6 
5.2 
Exclusion criteria .......................................................................................................... 6 
6 
ENROLLMENT ................................................................................................................... 8 
6.1 
Enrollment ................................................................................................................... 8 
7 
STUDY DRUG AND TREATMENT ..................................................................................... 9 
7.1 
Description of study drug ............................................................................................. 9 
7.2 
Shipping, handling, and storage ................................................................................... 9 
7.3 
Special precautions for storage .................................................................................... 9 
7.4 
Drug accountability ...................................................................................................... 9 
7.5 
Study drug dosage ....................................................................................................... 9 
7.6 
Study drug preparation and infusion ...........................................................................10 
7.7 
Incompatibilities ..........................................................................................................10 
7.8 
Administration .............................................................................................................10 
7.9 
Rate of administration .................................................................................................10 
7.1 
Concomitant therapy ...................................................................................................11 
8 
EVALUATIONS BY VISIT .................................................................................................11 
8.1 
VISIT 1: Screening ......................................................................................................11 
8.2 
VISIT 2: Day 1 – First infusion ....................................................................................12 
8.2.1 
Study drug infusion: .............................................................................................12 
8.2.2 
Following initiation of infusion: .............................................................................12 
8.3 
VISIT 3 (Day 14 - Second Infusion) through VISIT 6 (Day 56 - Fifth Infusion) .............13 
8.4 
VISIT 7: Month 4 (±7 days) ..........................................................................................13 
8.5 
Early termination from the study..................................................................................13 

Sutter Institute for Medical Research 
 
PI: Shawn Kile, MD 
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9 
WITHDRAWAL AND REPLACEMENT OF SUBJECTS ....................................................14 
9.1 
Criteria for subject withdrawal .....................................................................................14 
9.2 
Replacement of subjects .............................................................................................14 
10 
ADVERSE EVENTS .......................................................................................................14 
10.1 
Adverse event definition ..............................................................................................14 
10.2 
Serious adverse event (SAE) definition .......................................................................14 
10.3 
Other relevant drug safety information ........................................................................15 
10.4 
Adverse event severity ................................................................................................15 
10.5 
Adverse event reporting ..............................................................................................15 
10.6 
Investigator reporting to the FDA ................................................................................16 
10.7 
Reporting of adverse drug reactions and other safety information ...............................16 
10.8 
Reporting of adverse events to the institutional review board (IRB) ............................16 
10.9 
Reporting of adverse drug reactions and other safety information to study sponsor ....16 
10.10 
Adverse event updates ............................................................................................17 
11 
IND REPORTING ...........................................................................................................17 
12 
PROTOCOL DEVIATIONS ............................................................................................17 
13 
DATA RECORDING, RETENTION, AND MONITORING ...............................................17 
13.1 
Data entry and maintenance .......................................................................................17 
13.2 
Study records retention ...............................................................................................18 
13.3 
Data monitoring committee .........................................................................................18 
14 
STATISTICAL ANALYSIS .............................................................................................18 
14.1 
Primary endpoint .........................................................................................................18 
15 
SAMPLE SIZE ...............................................................................................................18 
16 
IMPLICATIONS AND DIRECTION FOR FUTURE STUDIES .........................................18 
17 
ETHICAL AND LEGAL ISSUES ....................................................................................18 
17.1 
Institutional review board approval ..............................................................................18 
17.2 
Informed consent ........................................................................................................19 
17.3 
Subject confidentiality .................................................................................................19 
17.4 
Protocol amendments .................................................................................................19 
17.5 
Premature discontinuation of study .............................................................................19 
18 
REFERENCES ...............................................................................................................20 
19 
APPENDIX A:  NINCDS-ADRDA criteria for diagnosis Alzheimer Disease 8 ..............21 
23.0 
APPENDIX B: Clinical laboratory tests .........................................................................22 
20 
APPENDIX C: INSTRUCTIONS FOR FLORBETAPIR PET ..........................................23 
21 
APPENDIX D: INSTRUCTIONS FOR RETINAL AMYLOID IMAGING ..........................24 
21.1 
Pupil dilation will be conducted prior to imaging. .........................................................24 

Sutter Institute for Medical Research 
 
PI: Shawn Kile, MD 
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21.2 
Imaging Procedure......................................................................................................24 
22 
Amendment 1 ................................................................................................................25 
 
1 
SCHEDULE OF STUDY ACTIVITIES 
 
Study Visit 
1 
2 
3 
4 
5 
6 
7 
Study Time Point 
Day -28 To Day 
-1 
Day  
1 
Day 
14 
Day 
28 
Day 
42 
Day
56 Month 3 
Visit Type (Visit Window) 
Screening 
Infusion Visits (±1 day) 
±7 days 
CLINICAL 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
X 
 
 
 
 
 
Medical Hx/Prior/Baseline 
Medications 
X 
 
 
 
 
 
 
NIA criteria review 
X 
 
 
 
 
 
 
Modified Hachinski 
Ischemia Scale 
X 
 
 
 
 
 
 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
Physical Exam 
X 
X 3 
 
 
 
 
X 
Neurological Exam 
X 
X 3 
 
 
 
 
X 
ECG 
X 
 
 
 
 
 
 
Florbetapir -PET (Appendix C) 
X 
 
 
 
 
 
X 
Retinal scan for amyloid 
(Appendix D) 
X 
 
 
 
 
 
X 
Mini Mental State Exam (MMSE) 
X 
 
 
 
 
 
 
CDR-SB 
X 
 
 
 
 
 
 
IGA deficiency 
X 
 
 
 
 
 
 
Serum viscosity 
X 
 
 
 
 
 
 
CBC, Chemistry Panel 
(Appendix B) 
X 
 
 
 
 
 
X 
TSH, Vit-B12, RPR 1 
X 
 
 
 
 
 
 
Urinalysis 2 
X 
 
 
 
 
 
 
Adverse events & 
Concomitant Meds 
 
X 
X 
X 
X 
X 
X 
THERAPY 
 
 
 
 
 
 
 
Infusion of IVIG 
 
X 
X 
X 
X 
X 
 
Assess infusion site 
 
X 
X 
X 
X 
X 
 
1 RPR, B12, TSH required if not done in the last 12 months prior to screening 
2 Urine culture may be performed if indicated 
3 May occur within 72 hours prior to first infusion 

Sutter Institute for Medical Research 
 
PI: Shawn Kile, MD 
Page 5                                                                                                                              v 9.22.17 
2 
BACKGROUND 
Alzheimer’s disease (AD) is a neurodegenerative disorder which causes cognitive decline and 
brain atrophy associated with the pathologic accumulation of amyloid and tau proteins. 
Passive immunization with intravenous immunoglobulin (IVIG) contains amyloid antibodies 
and has been investigated as a potential safe disease-modifying strategy for Aβ clearance in 
AD. 1,2  
We conducted the first study investigating early administration of IVIG given in the pre-
dementia stage, MCI (mild cognitive impairment), of AD. The details of this randomized, 
double-, placebo-controlled trial have been previously published. 3 Patients with MCI were 
randomized to receive either 0.4 g/kg of IVIG or 0.9% saline solution every 14 days x 5 
infusions. The results showed that there was less brain atrophy in participants given IVIG 
when compared with placebo at 12 months as well as evidence of a sustained effect at 36 
months based on our extension study results. 
We suspect the primary mechanism of action of IVIG to be clearance of amyloid. However 
other possible mechanisms of IVIG have been proposed. IVIG also contains tau antibodies 
and has other immunomodulating properties including regulating effects on microglia which 
may be beneficial in modulating neuroinflammation and neurodegeneration in AD. 4-7  
There has never been a published study in humans using amyloid imaging to demonstrate the 
treatment effects of IVIG in MCI. Here we propose use of both amyloid brain PET imaging and 
retinal amyloid imaging (a novel surrogate scanner used to determine amyloid burden) to 
determine if IVIG treatment results in a measurable reduction in amyloid. 
3 
STUDY OBJECTIVES AND ENDPOINTS 
 
     3.1  
Primary Objective 
This is a proof of concept study is to determine if changes in brain amyloid levels as measured 
by Florbetapir PET, as well as retinal amyloid levels in the retina are evident three months after 
infusion of 0.4 g/kg of IVIG every 14 days x 5 infusions. 
 
     3.2  
Primary Endpoints 
Change in standard uptake values (SURV) as measured by Florbetapir PET at baseline and 3 
months and Retinal Amyloid Index (RAI) as measured by amyloid levels in the retina. 
4 
STUDY PLAN 
 
     4.1  
Study design 
This is a single center, open label, proof of concept, out-patient study. Subjects will undergo 
Florbetapir PET and have retinal amyloid levels measured, receive an infusion of IVIG at 0.4 
g/kg every 14 days for a total of five infusions, and repeat PET and retinal amyloid measures 
three months after the first infusion. 
 
     4.2  
Subject population 
The study population will consist of male and female subjects diagnosed with mild cognitive 
impairment (MCI) due to Alzheimer disease (AD). 
 

Sutter Institute for Medical Research 
 
PI: Shawn Kile, MD 
Page 6                                                                                                                              v 9.22.17 
     4.3  
Estimated study duration 
The duration of each study subject is approximately 4 months, including one screening visit 
over a period of approximately 28 days, 5 days of infusions over a 2-month period of time, 
and a follow-up visit at 3 months after the first infusion. 
5 
SUBJECT SELECTION 
 
     5.1  
Inclusion criteria 
 
1. Age 50 to <85 years. 
2. Evidence of amyloid pathology on Florbetapir PET at screening. 
3. Diagnosis of MCI due to AD based on NIA-AA criteria. (APPENDIX A) 
4. MRI brain (with past 24 months) which shows evidence of mild hippocampal atrophy and/or 
bilateral parietal atrophy. 
5. CDR score of 0.5 
6. Mini-Mental State Examination (MMSE) score of 24-30, inclusive. 
7. Rosen Modified Hachinski Ischemic score ≤4. 
8. Receiving stable doses of medication(s) for the treatment of non-excluded medical 
condition(s) for at least 30 days prior to screening. Cholinesterase inhibitors and memantine 
are allowed if doses have stable been least 30 days prior to screening. 
9. Agree to refrain from participating in any treatment or clinical trial targeting amyloid for the 
duration of the study. 
10. Agree to refrain from taking any herbal supplement considered to enhance cognition unless 
approved by the investigator for the duration of the study. 
11. Ability to attend all clinical visits and have an informant capable of accompanying the subject 
on specific clinic visits. 
12. The subject’s collaborative informant (support person) must be someone who has known 
the subject for at least 4 years and has had approximately 2 or more separate 
communications with the study participant per month (at least one of these communications 
in person).  
13.  Fluency in English and evidence of adequate premorbid intellectual functioning. 
14. Adequate manual dexterity, visual, and auditory abilities to perform all aspects of the 
cognitive and functional assessments. 
15. Venous access suitable for repeated infusions and phlebotomy. 
16. In the opinion of the investigator, the subject and informant will be compliant and have a 
high probability of completing the study, including all scheduled evaluations and required 
tests. 
 
     5.2  
Exclusion criteria 
 
1. Has significant neurological disease other than MCI that in the opinion of the investigator 
may affect cognition. 
2.  History of clinically evident stroke or history of clinically significant carotid or vertebrobasilar 
stenosis or plaque. 

Sutter Institute for Medical Research 
 
PI: Shawn Kile, MD 
Page 7                                                                                                                              v 9.22.17 
3.  History of seizures, excluding febrile seizures in childhood. 
4.  History of screening visit brain MRI scan indicative of any other significant abnormality, 
including but not limited to multiple microhemorrhages (2 or more), history or evidence of a 
single prior hemorrhage > 1 cm3, multiple lacunar infarcts (2 or more) or evidence of a 
single prior infarct > 1 cm3, evidence of a cerebral contusion, encephalomalacia, 
aneurysms, vascular malformations, subdural hematoma, or space occupying lesions of 
significance as determined by the PI (e.g., arachnoid cysts or brain tumors such as 
meningioma).  
5. Brain MRI shows moderate or severe cortical or hippocampal atrophy. 
6. Sensitivity to Florbetapir. 
7. Other present/planned ionized radiation that, in combination with planned exposure to PET 
ligands for this study, would result in cumulative exposure that would exceed recommended 
limits. 
8. Ophthalmologic condition that would interfere with retinal amyloid imaging. 
9. Current presence of a clinically significant major psychiatric disorder (e.g., Major Depressive 
Disorder) according to the criteria of the Diagnostic and Statistical Manual of Mental 
Disorders, Fourth Edition (DSM-IV-TR) or symptom (e.g., hallucinations) that in the opinion 
of the investigator could affect the subject’s ability to complete the study. 
10. Current clinically significant systemic illness that is likely to result in deterioration of the 
subject’s condition or affect the subject’s safety during the study including but not limited to 
renal failure or myocardial infarction. 
11. History of cancer within the last 5 years, with the exception of nonmetastatic basal cell 
carcinoma, and squamous cell carcinoma of the skin. 
12. Uncontrolled hypertension (diastolic BP> 100 mmHg or systolic BP> 160 mmHg, sitting). 
13.  History or evidence of any clinically significant autoimmune disease or disorder of the 
immune system (e.g., Crohn’s Disease, Rheumatoid Arthritis) 
14. Clinically significant infection within the last 30 days (e.g., chronic persistent or acute 
infection (eg, upper respiratory infection [URI], urinary tract infection [UTI]). 
15.  Female subjects of childbearing potential. 
16. Other clinically significant abnormality on physical, neurological, laboratory, vital signs or 
ECG examination (e.g., atrial fibrillation) that could compromise the study or be detrimental 
to the subject. 
17. Weight greater than 120 kg (264 lbs). 
18. Excessive smoking defined as more than 20 cigarettes per day. 

Sutter Institute for Medical Research 
 
PI: Shawn Kile, MD 
Page 8                                                                                                                              v 9.22.17 
19. History of alcohol or drug dependence or abuse as defined by DSM-IV criteria within the last 
2 years. 
20. Severe liver or kidney disease verified by the PI review of ALT, AST and creatinine. 
21. Known coagulopathy, thrombosis, or low platelet count. 
22. Hemoglobin less than 11 g/dL. 
23. Known deficiency to IgA. 
24. Positive serology for Hepatitis B or C, or HIV. 
25. History of anti-amyloid treatment, immunotherapy, or other experimental treatment for MCI 
or Alzheimer disease. 
26. Concurrent use of anticholinergic drugs including diphenhydramine.  
27. Current use of anticoagulant medications (except the use of aspirin 325 mg/day or less, 
plavix, aggrenox, and persantine but not for stroke). 
28. Concurrent use of opioid pain relievers and related synthetic derivatives. 
6 
ENROLLMENT 
 
Prior to the start of enrollment, all study contracts must be fully executed and the following 
critical documents must be filed in the sponsor’s regulatory binder (trial master file): 
• 
Investigational new drug (IND) application approved by the FDA 
• 
Sutter Health Institutional Review Board (SHIRB) approval of the study protocol and 
the informed consent form (ICF) 
• 
Signed and dated study protocol 
• 
Completed Federal Drug Administration (FDA) Form 1572 
• 
Current curricula vitae and medical licenses (if applicable) of the Principal 
Investigator (PI) and all Sub-Investigators listed on the Form FDA 1572; 
• 
Name, address, and membership of the IRB, and/or written statement that IRB is 
properly constituted and operates according to Good Clinical Practices (GCP) 
• 
Investigator’s Brochure 
• 
Laboratory normal range and documentation of laboratory certification (or 
equivalent). 
• 
All applicable contracts 
 
     6.1  
Enrollment 
A subject is considered enrolled when they have completed informed consent and received 
any amount of IVIG by infusion. 

Sutter Institute for Medical Research 
 
PI: Shawn Kile, MD 
Page 9                                                                                                                              v 9.22.17 
7 
STUDY DRUG AND TREATMENT 
 
     7.1  
Description of study drug 
Octagam is an FDA approved 10% human normal immunoglobulin solution ready for 
intravenous administration. Adverse Drug Reactions (ADRs) reported for Octagam are 
expected to be similar in type and intensity to those reported with other IVIG preparations. 
The Octagam manufacturing process achieves a significant viral reduction through a 
combination of two dedicated manufacturing process steps: solvent/detergent (S/D) 
treatment and nanofiltration (20 nm). Based on the combination of these two steps, Octagam 
complies with the latest international consensus on best practices for viral safety. The 
Source Q chromatography (ion-exchange chromatography) step in the Octagam process 
also contributes significantly to the viral safety of Octagam. The efficacy of the virus 
inactivation procedures has been extensively validated according to relevant international 
guidelines in place. Further information can be found in the current Investigator’s Brochure. 
 
     7.2  
Shipping, handling, and storage 
Octagam will be shipped directly to the pharmacy or investigational site, after all required 
regulatory and legal documents have been received by the Sponsor. 
Upon receipt of the study drug shipments, the pharmacist will verify the condition of the study 
drug and perform study drug accountability. Acknowledgement of receipt will be documented 
in the Pharmacy Binder. A temperature logger showing the transport temperature will be read 
out by the shipper and release the drug if the transport temperature is verified to be between 
+2°C to + 8°C (36°F to 46°F). If there was a deviation from this temperature range, an 
Octapharma Project Manager or Qualified Person must assess the temperature log and 
approve release. 
The study drug will be stored in a secure area with access restricted only to authorized 
personnel. Octagam may be stored for 15 months at +2°C to + 8°C (36°F to 46°F) from the 
date of manufacture. 
 
     7.3  
Special precautions for storage 
• 
Do not freeze. Frozen product should not be used 
• 
Do not use after expiration date 
 
     7.4  
Drug accountability 
The investigator is responsible to ensure supervision of accurate monitoring of the receipt, 
storage and allocation of the study drug. Copies of all invoices of study drug shipments must 
be retained. Accurate study drug inventory, dispensing and accountability logs must be 
obtained and stored in the Pharmacy Binder. 
 
     7.5  
Study drug dosage 
The dose level of IVIG at 0.4 g/kg will be administered by IV infusion once every 14 days for 
two months. Subject’s weight at the first infusion visit will be used for the dosing calculation for 
the remaining infusions. There is no provision for dose adjustments by the investigator under 
this protocol. 

Sutter Institute for Medical Research 
 
PI: Shawn Kile, MD 
Page 10                                                                                                                              v 
9.22.17 
 
     7.6  
Study drug preparation and infusion 
• 
The pharmacist will prepare the IVIG for each infusion. 
• 
The IVIG should be inspected visually for particulate matter and discoloration prior 
to administration, whenever solution and container permit. Do not use if turbid 
and/or discoloration is observed. 
• 
The IVIG must not be mixed with other medicinal products or administered 
simultaneously with other intravenous preparation in the same infusion set. Do not 
mix with IVIG products from other manufacturers. 
• 
Do not freeze. Solutions that have been frozen should not be used. 
• 
IVIG bottle is for single use only. Octagam contains no preservative. Any bottle that 
has been entered should be used promptly. Partially used bottles should be 
discarded. 
• 
Content of IVIG bottles may be pooled under aseptic conditions into sterile infusion 
bags and infused within 8 hours after pooling (within 72 hours if stored at 2-8°C [36-
46°F]). 
• 
Do not use after expiration date. 
• 
IVIG should not be diluted. 
• 
IVIG must be allowed to warm to room or body temperature prior to infusion if stored 
at 2-8°C (36-46°F). 
• 
0.4 g/kg body weight of Octagam 10% is transferred into an EVA infusion bag. 
 
     7.7  
Incompatibilities 
Octagam must not be mixed with other medicinal products or administered simultaneously 
with other intravenous preparations in the same infusion set. 
 
     7.8  
Administration 
• 
Octagam should be at room or body temperature during administration. Only 
administer intravenously. 
• 
Any bottle that has been opened should be used promptly. Partially used bottles 
should be discarded. 
• 
Octagam is not supplied with an infusion set. If an in-line filter is used the pore 
size should be 0.2 – 200 microns. 
• 
Do not use a needle of larger than 16 gauge to prevent the possibility of coring. Insert 
needle only once, within the stopper area delineated (by the raised ring for 
penetration). The stopper should be penetrated perpendicular to the plane of the 
stopper within the ring. 
 
     7.9  
Rate of administration 
The initial infusion rate of IVIG (Octagam) will be 0.01 mL/kg/min (60 mg/kg/hr) for the first 30 
minutes; if tolerated, advanced to 0.02 mL/kg/min (120 mg/kg/hr) for the second 30 minutes; 

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PI: Shawn Kile, MD 
Page 11                                                                                                                              v 
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if tolerated, advanced to 0.03 mL/kg/min (180 mg/kg/hr) for the third 30 minutes and, if 
tolerated, advanced to 0.04 mL/kg/min (240 mg/kg/hr) for the remaining time at the discretion 
of the treating Investigator. 
If adverse events (AEs) occur during infusion, the rate should be reduced to half the rate at 
which the event occurred, or the infusion interrupted until symptoms subside. The infusion 
may then be resumed at a rate tolerated by the patient. 
The batch number(s) and number of different vial sizes used will be recorded on the drug 
accountability form. 
 
     7.1  
Concomitant therapy 
Concomitant medications will be assessed at all study visits. Concomitant medications are 
prescribed or over-the-counter medications and should be consistent with the 
inclusion/exclusion criteria. Concomitant medication appropriate to the subject’s condition may 
be prescribed during the course of the study with the exception of those listed above. 
 
Routine vaccinations (i.e., flu vaccination) with commercially available therapeutics are permitted 
but must not be given within four weeks before or after the administration of the study drug.  
8 
EVALUATIONS BY VISIT 
 
The overall summary of study activities by visit is provided Section 1. 
 
Screening procedures at visit 1 will take place up to 28 days prior to Visit 2 (Day 1) dosing. 
Screening labs and assessments will be performed during the screening period. The first 
dose of study drug is administered on Day 1. Visits 2 through 6 have a ±1 day window and 
occur every 14 days over two months. The investigator will determine if a subject is suitable to 
continue following a missed infusion. Visit 7 has a ±7 day window. 
 
All study screening data from Visit 1 including laboratory results must be reviewed for study 
eligibility prior to receiving first dose of study drug. Prior to infusion, a review of concomitant 
medications and AEs takes place. If the subject continues to be eligible for enrollment, the 
subject will be infused with study medication and will remain in the infusion clinic for at least 1 
hour following the infusion for safety assessments on Visit 2 (Day 1), and 15 minutes for the 
subsequent visits. 
 
     8.1  
VISIT 1: Screening 
The following screening procedures will occur up to 28 days prior to Visit 2 (Day 1) infusion: 
• 
Obtain signed and dated SHIRB approved written Informed Consent from the 
subject and collaborative informant prior to the initiation of any screening procedure 
• 
Assess Inclusion/Exclusion criteria 
• 
Obtain medical history 
• 
Record prior medications 
• 
NIA criteria review 
• 
Determine Rosen Modified Hachinski Ischemic score 

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PI: Shawn Kile, MD 
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• 
Record vital signs 
• 
Perform physical examination including height and weight 
• 
Perform neurological examination 
• 
Obtain standard 12-lead ECG 
• 
Conduct MMSE and CDR assessments 
• 
Conduct Florbetapir PET (Appendix C) 
• 
Conduct retinal amyloid imaging (Appendix D) 
• 
Obtain blood sample for ApoE genotyping, IgA deficiency, serum viscosity 
• 
Obtain blood sample for complete blood count (CBC) and comprehensive 
metabolic panel (chemistry panel).  
• 
Obtain blood sample for thyroid stimulating hormone (TSH), vitamin-B12 and 
rapid plasma reagin laboratory tests 
 
     8.2  
VISIT 2: Day 1 – First infusion 
The investigator will confirm that subjects are still eligible by reviewing all screening data. 
Subjects who no longer meet criteria will not be eligible for enrollment in the study. 
 
• 
Confirm that subjects continue to meet inclusion/exclusion criteria 
• 
Assess and record AEs 
• 
Record concomitant medications 
• 
Record vital signs 
• 
Perform physical and neurological examinations (may occur within 72 hours prior to 
first infusion) 
• 
Preparation of study drug by pharmacists and deliverer to the infusion 
administration site. 
8.2.1 Study drug infusion: 
• 
Subjects will be given the option of prophylaxis oral acetaminophen, 
diphenhydramine, or both 15-30 minutes prior to infusion 
• 
Measure blood pressure, pulse rate, temperature and respiratory rate within 15 
minutes prior to start of the infusion 
• 
Administer study drug to the subject by intravenous infusion 
8.2.2 Following initiation of infusion: 
• 
Measure blood pressure and pulse rate at 15, 30, 60 and every 30 minute mark for 
the duration of the infusion 
• 
Measure blood pressure, pulse rate, temperature and respiratory rate immediately 
post infusion and prior to leaving the clinic 
• 
Assess infusion site post infusion 
• 
Assess and record AEs 

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PI: Shawn Kile, MD 
Page 13                                                                                                                              v 
9.22.17 
• 
Subjects will remain in the clinic for at least 1 hour following the completion of the 
infusion. The subjects may leave the clinic after the observation period if the subject 
is medically stable. 
 
     8.3  
VISIT 3 (Day 14 - Second Infusion) through VISIT 6 (Day 56 - Fifth Infusion) 
• 
Assess and record AEs 
• 
Record concomitant medications 
• 
Record vital signs 
• 
If there is any abnormality of vital signs or clinical concerns during infusion visit, 
the principle-investigator or sub-investigator will be paged in order to perform a 
clinical assessment. 
• 
Preparation of study drug by pharmacists and deliverer to the infusion 
administration site. 
• 
Administer drug as stated in 8.2.1 and 8.2.2 
• 
Subjects will remain in the clinic for at least 15 minutes following the completion of 
the infusion. The subjects may leave the clinic after the observation period if the 
subject is medically stable. 
 
     8.4   
VISIT 7: Month 4 (±7 days) 
• 
Assess and record AEs 
• 
Record concomitant medications 
• 
Record vital signs 
• 
Perform physical and neurological examinations 
• 
Record vital signs 
• 
Assess and record AEs 
• 
Record concomitant medications 
• 
Obtain blood sample for routine hematology and chemistry laboratory tests 
• 
Conduct Florbetapir PET (Appendix C) 
• 
Conduct retinal amyloid imaging (Appendix D) 
 
     8.5  
Early termination from the study 
Every attempt should be made to follow each subject through the final visit 7. In the event of 
early withdrawal from the subject for any reason, an Early Termination Visit should be 
completed for criteria of withdrawal. If the subject withdraws due to an AE, every attempt 
should be made to follow the subject until the AE resolves or until the investigator deems that 
the AE is stable or determined the AE to be chronic. All SAEs will continue to be followed until 
the end of the study (Visit 7 or ET visit) or until the SAE has resolved or the investigator 
deems the event to be stable or chronic. 

Sutter Institute for Medical Research 
 
PI: Shawn Kile, MD 
Page 14                                                                                                                              v 
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9 
WITHDRAWAL AND REPLACEMENT OF SUBJECTS 
 
     9.1  
Criteria for subject withdrawal 
In accordance with the Declaration of Helsinki and other applicable regulations, a subject has 
the right to withdraw from the study at any time and for any reason. If a subject requests or 
decides to withdraw, every attempt will be made to complete an early termination visit. 
The investigator has the right to withdraw subjects from the study if a subject: 
• 
Is in significant violation of the protocol 
• 
Experiences an intolerable AE or SAE 
• 
Is non-compliant 
• 
Withdrawal of consent 
• 
Lost to follow up 
• 
Death 
 
     9.2  
Replacement of subjects 
Subjects who do not complete all five infusions will be replaced. 
10 ADVERSE EVENTS 
 
     10.1 
Adverse event definition 
An AE is any untoward event that occurs any time after randomization to the double blind 
treatment until the end of study (visit 7 or ET visit). The event need not have a causal 
relationship with the study drug or treatment. Adverse events include, but are not limited to 
clinically significant changes in clinical status, physical or neurological examinations, ECG, 
abnormal laboratory findings, exacerbations of underlying disease, and drug interactions, 
dependency, misuse and abuse. All AEs must be documented on the Adverse Event page of 
the CRF and in the subject’s medical notes. Each AE is evaluated for duration, severity, 
seriousness, relatedness to study drug, and action taken. The investigator may be asked to 
provide follow-up information. 
 
     10.2 
Serious adverse event (SAE) definition 
A serious adverse event is one that at any dose (including overdose): 
• 
Results in death 
• 
Is life-threatening1 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• 
Results in persistent or significant disability or incapacity2 
• 
Is a congenital anomaly/birth defect 
• 
Is a medically important condition: 
Suspected transmission of an infectious agent, 
Thromboembolic events, 

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Cerebral hemorrhage resulting in clinical disability, or 
Other reactions that should be reported in an expedited manner although 
they did not immediately result in one of the above seriousness criteria 
     10.3 
Other relevant drug safety information 
Any safety information relating to: 
• 
Pregnancies/breastfeeding, 
• 
Drug abuse (persistent, sporadic or intentional excessive use of a medicinal 
product inconsistent with the SPC or acceptable medical practice), 
• 
Overdose (treatment exceeding the medically recommended dose), 
• 
Medication errors (prescribing or dispensing error), 
• 
Interactions with other medicinal products or devices 
• 
Associated with Octagam 10%, even if no adverse drug reaction occurred. 
 
1“Life-threatening” means that the subject was at immediate risk of death at the time of the serious adverse event; it 
does not refer to a serious adverse event that hypothetically might have caused death if it were more severe. 
2“Persistent or significant disability or incapacity” means that there is a substantial disruption of a person’s ability to 
carry out normal life functions. 
 
     10.4 
Adverse event severity 
Severity of AEs will be assessed using the National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE) Version 4.0 for toxicity and adverse event 
reporting. A copy of the CTCAE Version 4.0 can be downloaded from the CTEP homepage 
(http://ctep.info.nih.gov). AEs not corresponding to the CTCAE term will be assessed 
according to their impact on the subject’s ability to perform daily activities as follows: 
• 
Mild (grade 1) – the AE does not interfere in a significant manner with 
the subject’s normal functioning level. It may be an annoyance. 
• 
Moderate (grade 2) – the AE produces some impairment of functioning, 
but is not hazardous to health. It is uncomfortable or an embarrassment. 
• 
Severe (grade 3) – the AE produces significant impairment of functioning 
or incapacitation and is a definite hazard to the subject’s health. 
• 
Life threatening (grade 4) – Life threatening or disabling. 
• 
Fatal (grade 5) Causes death of the participant. 
The investigator must appraise all abnormal laboratory results for their clinical significance. If 
any abnormal laboratory result is considered clinically significant, the investigator must 
provide details about the action taken with respect to the test drug and about the patient’s 
outcome. 
 
     10.5 
Adverse event reporting 
All AEs, whether observed by the investigator or reported by the patient, must be recorded, 
with details about the duration and intensity of each episode, the action taken with respect to 
the test drug, and the patient’s outcome. The investigator must evaluate each adverse 
experience for its relationship to the test drug and for its seriousness. The initial report must 

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be as complete as possible, including details of the current illness and (serious) adverse 
event, and an assessment of the causal relationship between the event and the 
investigational product(s). Information not available at the time of the initial report (e.g., an 
end date for the adverse event or laboratory values received after the report) must be 
documented on a follow- up form. A final report to document resolution of the adverse event 
is required. 
 
     10.6 
Investigator reporting to the FDA 
Adverse drug reactions that are serious, unlisted/unexpected, and at least possibly 
associated to the drug, and that have not previously been reported in the Investigators 
brochure, or reference safety information document should be reported promptly to the FDA in 
writing by each investigator/physician engaged in clinical research. A clear description of the 
suspected reaction should be provided along with an assessment as to whether the event is 
drug or disease related. 
The investigator/physician shall notify the FDA by telephone or by fax of any unexpected fatal 
or life threatening experience associated with the use of the drug as soon as possible, but no 
later than 7 calendar days after the sponsors initial receipt of the information. Each phone call 
or fax shall be transmitted to the FDA new drug review division in the Center for Drug 
Evaluation and Research or the product review division in the Center for Biologics Evaluation 
and Research that has responsibility for review of the IND if applicable. 
 
     10.7 
Reporting of adverse drug reactions and other safety information  
All suspected AEs and other safety information associated with the administration of Octagam 
have to be reported to: 
Central Drug Safety Unit: 
Email: 
cdsu@octapharma.com 
Fax: +43-1-61032-9949 
Serious adverse drug reactions have to be reported immediately by fax or email (within 24 hrs). 
Non-serious adverse drug reactions and other safety information should be reported to 
Octapharma, if possible, upon recognition but no later than 10 days. 
 
     10.8 
Reporting of adverse events to the institutional review board (IRB) 
The principal investigator is required to notify the Sutter Health Institutional Review 
Committee (SHIRB) of a serious adverse event according to institutional policy. 
 
     10.9 
Reporting of adverse drug reactions and other safety information to study 
sponsor 
Octapharma shall notify the Investigator via an IND Safety Report of the following 
information: 
• 
Any AE associated with the use of study drug in any studies involving Octagam 10% 
that is both serious and unexpected. 
• 
Any finding from tests in laboratory animals that suggests a significant risk for 
human subjects including reports of mutagenicity, teratogenicity, or 

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carcinogenicity. 
 
     10.10 
Adverse event updates 
The investigator must keep copies of all AE information, including correspondence with 
Octapharma and the SHIRB, on file. 
The investigator shall notify the SHIRB promptly of any new serious and unexpected AE(s) or 
significant risks to subjects. 
11 IND REPORTING 
The conduct of the study will comply with all FDA safety reporting requirements. 
If the FDA has granted an IND number, it is a requirement of 21 CFR 312.33, that a study 
completion report is provided to the FDA within 60-days of study completion. 21 CRF 312.33 
provides the data elements that are to be submitted in the report. The completion report should 
be filed in the study's Regulatory Binder, and a copy provided to Octapharma as a supporter of 
this study as follows: 
 
Octapharma Pharmazeutika Produktionsges.m.b.H 
attn: Dr. Barbara Rangetiner (General Manager OPG / Director Int. Drug 
Regulatory Affairs)  
Oberlaaer Strasse 235 
A-1100 Vienna, Austria 
 
All AE reports must include the patient number, age, sex, weight, severity of reaction (mild, 
moderate, severe), relationship to study drug (probably related, unknown relationship, 
definitely not related), date and time of administration of test medications and all concomitant 
medications, and medical treatment provided. The investigator is responsible for evaluating all 
adverse events to determine whether criteria for “serious” and as defined above are present. 
12 PROTOCOL DEVIATIONS 
 
When an emergency occurs that requires a deviation from the protocol for a subject, a 
deviation will be made only for that subject. A decision will be made as soon as possible to 
determine whether or not the subject (for whom the deviation from protocol was effected) is to 
continue in the study. The subject’s medical records will completely describe the deviation 
from the protocol and state the reasons for such deviation. In addition, the Investigator will 
notify the SHIRB in writing of such deviation from protocol. 
Non-emergency minor deviations from the protocol will be permitted with approval of the 
principal investigator. 
13 DATA RECORDING, RETENTION, AND MONITORING 
 
     13.1 
Data entry and maintenance 
Investigator responsibilities are set out in the ICH guideline for Good Clinical Practice (GCP) 
and in the US Code of Federal Regulations. 

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Study personnel will construct case report forms (CRFs), record all study data onto the CRFs 
and enter the data into a 21 CFR Part 11 compliant database. 
 
     13.2 
Study records retention 
The investigator must ensure that the records and documents pertaining to the conduct of the 
study and the distribution of the study drug, that is copies of CRFs and source documents 
(original documents, data, and records [e.g., hospital records; clinical and office charts; 
laboratory notes; memoranda; subject’s diaries or evaluation checklists; SAE reports, 
pharmacy dispensing records; recorded data from automated instruments; copies or 
transcriptions certified after verification as being accurate copies; microfiches; photographic 
negatives, microfilm, or magnetic media; x-rays; subject files; and records kept at the 
pharmacy, at the laboratories, and at medico-technical departments involved in the clinical 
study; documents regarding subject treatment and study drug accountability; original signed 
informed consents, etc.]) be retained by the investigator for as long as needed to comply with 
national and international regulations (generally 2 years after discontinuing clinical 
development or after the last marketing approval). The investigator agrees to adhere to the 
document/records retention procedures by signing the protocol. 
 
     13.3 
Data monitoring committee 
The Data Monitoring Committee (DMC) will be composed of independent reviewers who will 
meet to review the efficacy and safety data and determine a risk/benefit analysis in this 
subject population. The purpose of the DMC is to advise on serious safety considerations, lack 
of efficacy, and any other considerations within the charge to the Committee. The DMC may 
request additional meetings or safety reports as deemed necessary upon discussion with the 
investigator or Octapharma and its representatives. The DMC may stop the study following 
review of results from the interim analysis. 
14 STATISTICAL ANALYSIS 
 
     14.1 
Primary endpoint 
Graphs of individual changes in standard uptake ratio values (SURV) of Florbetapir PET will be 
compared between baseline and 3 months. Graphs of individual changes in RAI values will be 
compared between baseline and 3 months.  
15 SAMPLE SIZE 
Five subjects will be included. If it appears that IVIG shows changes in these two markers, a 
large trial will be considered. 
16 IMPLICATIONS AND DIRECTION FOR FUTURE STUDIES 
This study will help determine if the reason that IVIG treatment appears to reduce brain atrophy 
in patients with MCI is due to a reduction of CNS (central nervous system) amyloid levels. 
17 ETHICAL AND LEGAL ISSUES 
The study will be submitted to the SHIRB. A data safety monitoring committee will be 
convened to provide oversight of subjects’ safety before commencement of the study. 
     17.1 
Institutional review board approval 
The protocol for this study has been designed in accordance with the general ethical 

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principles outlined in the Declaration of Helsinki. The review of this protocol by the SHIRB and 
the performance of all aspects of the study, including the methods used for obtaining informed 
consent, must also be in accordance with principles enunciated in the declaration, as well as 
ICH Guidelines, Title 21 of the Code of Federal Regulations (CFR), Part 50 Protection of 
Human Subjects and Part 56 Institutional Review Boards. 
The investigator will be responsible for preparing documents for submission to the SHIRB and 
obtaining written approval for this study. The approval will be obtained prior to the initiation of 
the study. 
The approval for both the protocol and informed consent must specify the date of approval, 
protocol number and version, or amendment number. 
Any amendments to the protocol after receipt of SHIRB approval must be submitted by the 
Investigator to the SHIRB for approval. The Investigator is also responsible for notifying the 
SHIRB of any serious deviations from the protocol, or anything else that may involve added 
risk to subjects. 
Any advertisements used to recruit subjects for the study must be reviewed and approved by 
the SHIRB prior to use. 
 
     17.2 
Informed consent 
Informed consent of a subject or his/her designee prior to any study related procedures must 
be obtained per GCPs as set forth in the CFR and ICH guidelines. 
Documentation that informed consent occurred prior to the subject’s entry into the study and 
the informed consent process should be recorded in the subject’s source documents. The 
original consent form signed and dated by the subject and by the person consenting the 
subject prior to the subject’s entry into the study, must be maintained in the investigator’s 
study files. 
 
     17.3 
Subject confidentiality 
Octapharma affirms the subject’s right to protection against invasion of privacy. In compliance 
with United States federal regulations, Octapharma requires the investigator to permit 
Octapharma representatives and, when necessary, representatives of the FDA or other 
regulatory authorities to review and/or copy any medical records relevant to the study in 
accordance with local laws. 
Should direct access to medical records require a waiver or authorization separate from the 
subject’s statement of informed consent, it is the responsibility of the Investigator to obtain 
such permission in writing from the appropriate individual. 
 
     17.4 
Protocol amendments 
Any amendment to this protocol must be agreed to by the principal investigator and reviewed 
by Octapharma. Amendments should only be submitted to the SHIRB after consideration of 
Octapharma review. Written verification of SHIRB approval will be obtained before any 
amendment is implemented. 
 
     17.5 
Premature discontinuation of study 
The responsible local clinical investigator and Octapharma have the right to 

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discontinue this study at any time for reasonable medical or administrative reasons. 
Possible reasons for termination of the study could be but are not limited to: 
• 
Unsatisfactory enrollment with respect to quantity or quality. 
• 
Inaccurate or incomplete data collection. 
• 
Falsification of records. 
• 
Failure to adhere to the study protocol. 
• 
Statistical analysis demonstrates overwhelming efficacy of treatment. 
Any possible premature discontinuation would be documented adequately with 
reasons being stated, and information would have to be issued according to local 
requirements (e.g., SHIRB/EC, regulatory authorities, etc.). 
 
18 REFERENCES 
 
1. 
Dodel R, Hampel H, Depboylu C, et al. Human antibodies against amyloid beta peptide: 
a potential treatment for Alzheimer's disease. Annals of neurology. Aug 2002;52(2):253-
256. 
2. 
Istrin G, Bosis E, Solomon B. Intravenous immunoglobulin enhances the clearance of 
fibrillar amyloid-beta peptide. J Neurosci Res. Aug 1 2006;84(2):434-443. 
3. 
Kile S, Au W, Parise C, et al. IVIG treatment of mild cognitive impairment due to 
Alzheimer's disease: a randomised double-blinded exploratory study of the effect on 
brain atrophy, cognition and conversion to dementia. Journal of neurology, 
neurosurgery, and psychiatry. Sep 29 2015. 
4. 
Negi VS, Elluru S, Siberil S, et al. Intravenous immunoglobulin: an update on the clinical 
use and mechanisms of action. Journal of clinical immunology. May 2007;27(3):233-245. 
5. 
Boche D, Denham N, Holmes C, Nicoll JA. Neuropathology after active Abeta42 
immunotherapy: implications for Alzheimer's disease pathogenesis. Acta 
neuropathologica. Sep 2010;120(3):369-384. 
6. 
Magga J, Puli L, Pihlaja R, et al. Human intravenous immunoglobulin provides protection 
against Abeta toxicity by multiple mechanisms in a mouse model of Alzheimer's disease. 
J Neuroinflammation. 2010;7:90. 
7. 
Smith LM, Coffey MP, Klaver AC, Loeffler DA. Intravenous immunoglobulin products 
contain specific antibodies to recombinant human tau protein. International 
immunopharmacology. Aug 2013;16(4):424-428. 
8. 
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical 
diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the 
auspices of Department of Health and Human Services Task Force on Alzheimer's 
Disease. Neurology. Jul 1984;34(7):939-944. 
 
 
 
 

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19 APPENDIX A:  NINCDS-ADRDA criteria for diagnosis Alzheimer Disease 8 
 
• 
Dementia established by clinical examination and documented by the Mini-Mental 
State Test, Blessed Dementia Scale or some similar examination, and confirmed by 
neuropsychological tests 
• 
Deficits in two or more areas of cognition 
• 
Progressive worsening of memory and other cognitive functions 
• 
No disturbance of consciousness 
• 
Onset between ages 40 and 90, most often after age 65 
• 
Absence of systemic disorders or other brain diseases that in and of themselves 
could account for the progressive deficits in memory and cognition 
20.0.1 
The diagnosis of probable Alzheimer disease is supported by: 
• 
Progressive deterioration of specific cognitive skills such as language (aphasia), 
motor skills (apraxia), and perception (agnosia) 
• 
Impaired activities of daily living and altered patterns of behavior 
• 
Family history of similar disorders, particularly if confirmed neuropathologically 
• 
Laboratory results of: 
1. Normal lumbar puncture as evaluated by standard techniques 
2. Normal pattern or nonspecific changes in EEG, such as increased slow-
wave activity 
3. Evidence of cerebral atrophy on CT with progression documented by 
serial Observation 
20.0.2 
Other clinical features consistent with the diagnosis of probable 
Alzheimer disease, after exclusion of causes of dementia other than 
Alzheimer disease: 
• 
Plateaus in the progression of the illness 
• 
Associated symptoms of depression, insomnia, incontinence, delusions, illusions, 
hallucinations; catastrophic verbal, emotional, or physical outbursts, sexual 
disorders, and weight loss 
• 
Other neurologic abnormalities in some patients, especially with more advanced 
disease and including motor signs such as increased muscle tone, myoclonus, or gait 
disorder 
• 
Seizures in advanced disease 
• 
CT normal for age 
20.0.3 
Features that make the diagnosis of probable Alzheimer 
disease uncertain or unlikely include: 

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• 
Sudden, apoplectic onset 
 
 
• 
Focal neurologic findings such as hemiparesis, sensory loss, visual field deficits, 
and incoordination early in the course of the illness 
• 
Seizures or gait disturbances at the onset or very early in the course of the illness 
20.0.4 
5. Criteria for diagnosis of definite Alzheimer disease are: 
• 
The clinical criteria for probable Alzheimer disease and, in addition, 
histopathological evidence obtained from a biopsy or autopsy. 
 
23.0 APPENDIX B: Clinical laboratory tests 
 
Comprehensive 
Metabolic Panel 
Complete Blood Count with 
differential 
Urinalysis 
Sodium 
WBC 
Urine microscopy 
Potassium 
RBC 
Culture if indicated 
Chloride 
Hemoglobin 
CO2 
Hematocrit 
Glucose 
MCV 
BUN 
MCH 
Creatinine 
RDW 
Calcium 
Platelet Count 
Total Protein 
Neutrophil % 
Albumin 
Lymphocytes % 
Total Bilirubin 
Monocyte % 
Alkaline Phosphatase 
Eosinophil % 
AST 
Basophil % 
ALT 
Neutrophil Count 
Lymphocyte Count 
Monocyte Count 
Eosinophil Count 
  
Basophil Count  
 
 
 
 
 
 
 
 
 
 
 
 
 

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20 APPENDIX C: INSTRUCTIONS FOR FLORBETAPIR PET 
Imaging will be acquired on a Siemens Biograph mCT (Ultra High-Definition PET/40 slice 
CT) scanner. Dosing will be 10 mCi Florbetapir in a peripheral vein with saline flush. A 10-
minute acquisition will be obtained 30 to 50 minutes after administration. Image data will be 
processed by iterative reconstruction with all corrections (TOF, PSF modeling, scatter) 256 
matrix, 2X zoom, 2.0 Gaussian filter. Images will be interpreted by a radiologist/nuclear 
medicine physician trained to read Florbetapir studies. Patients with positive studies 
(moderate to frequent beta amyloid neuritic plaques) will be included in the study and will 
undergo a repeat Florbetapir PET/CT brain imaging study 3 months later after treatment with 
either IVIG or placebo.  
 Analysis: Florbetapir is normally washed out of the cerebellar cortical gray matter in both 
healthy controls (HC) and in Alzheimer’s dementia patients (AD). As such, it is used as the 
reference region for SUVR calculation. Regions of interest will be drawn around areas of 
cerebral gray matter in the frontal, lateral temporal, parietal and parieto-occipital regions 
using the fused PET/CT images and SUVRs will be calculated using the ratio of these SUV 
values to the value in the cerebellar gray standard uptake value.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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21 APPENDIX D: INSTRUCTIONS FOR RETINAL AMYLOID IMAGING 
 
NeuroVision Imaging, LLC is providing the equipment and software analysis for retinal amyloid imaging. 
 
     21.1 
Pupil dilation will be conducted prior to imaging. 
Administer: 
1. Proparacaine 0.5% - numbing – 1 drop OU -wait 2 minutes 
2. Tropicamide 0.5% (Mydriacyl) –1 drop OU– wait 3 minutes 
3. Phenylephrine HCl 2.5% - 1 drop OU – wait until dilated >3.5 mm 
     21.2 
Imaging Procedure  
The imaging shall use the Retia device with software version 1.4.5 or later.  
For each study scan, capture autofluorescence images of the Superior field in 3 focal plans, up to 
6 images each 
a. Image set 1 of 3  
i. First image – Full automatic IR and AFL of superior field.  
 
ii. Images 2 to up to 6  
 
1. Review the fully automatic IR image and read/record the machine diopter set point (to 
the tenths digit, e.g. 2.4)  
 
2. Start a new exam, select Superior, and then go to Manual Alignment and Focus 
mode  
 
a. Use the slider and joystick buttons to enter the previously recorded autofocus 
value to the nearest tenth of an MD.  
 
b. Use the on-screen buttons and take one IR and then the sequence of 5 AFL 
images (one every 5 -10 seconds, the LED cycle time).  
b. Image set 2 of 3 i. Without exiting the exam,  
ii. Move the focus point -2 MD using the slider and/or the joystick buttons (e.g. if the initial 
focus point was 2.4, then move the focus point to 0.4).  
iii. Use the on-screen buttons to take one IR and then the sequence of up to 6 AFL images, 
one every 5 or so seconds.  
c. Image set 3 of 3  
i. Without exiting the exam,  
ii. Move the focus point +4 MD (+2 MD from the original recorded focus point, 4.4 in our 
example here) using the slider and/or the joystick buttons.  
iii. Use the on-screen buttons to take one IR and then the sequence of up to 6 AFL images.  
 
 
 
 

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22 Amendment 1 
 
• 
NewGam 10% changed to Octagam 10%