18F-AV-1451 Autopsy Study

Study Overview
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Brief Summary
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This study is designed to test the relationship between ante-mortem flortaucipir Positron Emission Tomography (PET) imaging and tau neurofibrillary pathology associated with Alzheimer's disease (AD), as measured at autopsy.

Official Title
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A Clinico-Pathological Study of the Correspondence Between 18F-AV-1451 PET Imaging and Post-Mortem Assessment of Tau Pathology

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: Flortaucipir F18
* Procedure: PET Scan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a projected life expectancy of ≤ 6 months Can tolerate a 20 minute PET scan Give informed consent or have a legally authorized representative to consent for study procedures and brain donation consistent with the legal requirements of the State in which they die Exclusion Criteria: Aggressively being treated with life sustaining measures Known to have a structural brain lesion that would interfere either with PET imaging or pathological assessment Clinically significant infectious disease Currently receiving any investigational medications except with permission from the study sponsor Participated in an experimental study with an amyloid or tau targeting agent Suspected encephalopathy due to alcoholism or end-stage liver disease Females of childbearing potential History of risk factors for Torsades de Pointes or are currently taking medication known to cause QT prolongation

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Flortaucipir PET Scan<br> | Drug: Flortaucipir F18<br>* 370 megabecquerel (MBq) IV single-dose<br>* Other names: LY3191748;Procedure: PET Scan<br>* positron emission tomography (PET) scan<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Outcome 1: Diagnostic Performance of Individual Readers (NFT Score) | Sensitivity and specificity of 5 independent readers' interpretations of ante-mortem flortaucipir PET imaging for detection of a pattern of flortaucipir neocortical uptake that corresponds to neurofibrillary tangles (NFT) Score of B3 (Hyman et al., 2012; Montine et al., 2012). NFT B scores range from B0 (Braak Stage 0; no NFTs in the brain) to B3 (Braak Stage V/VI; widespread NFTs in the brain). Sensitivity and specificity are percentages that can range from 0 to 100%. The hypothesis tested was that, of the 5 independent imaging physicians, at least 3 will have the lower bounds of 2-sided 95% CIs ≥50%, for both sensitivity and specificity. | at autopsy within 9 months of baseline scan | 
| Primary Outcome 2: Diagnostic Performance of Individual Readers (NIA-AA Autopsy Diagnosis) | Sensitivity and specificity of 5 independent readers' interpretations of ante-mortem flortaucipir imaging for detection of a pattern of flortaucipir neocortical uptake that corresponds to high levels of Alzheimer's disease neuropathologic change (High ADNC) as defined by National Institute on Aging-Alzheimer's Association (NIA-AA) criteria. ADNC categories are None, Low, Intermediate and High, with High indicating the most severe level of AD-related pathology changes in the brain (Hyman et al., Alzheimers Dement. 2012 Jan;8(1):1-13). The hypothesis tested was that, of the 5 independent imaging physicians, at least 3 will have the lower bounds of 2-sided 95% CIs ≥50%, for both sensitivity and specificity. | at autopsy within 9 months of baseline scan | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Flortaucipir Diagnostic Performance (NFT Score) | Sensitivity and specificity of majority interpretation of AD pattern tau PET scan corresponding to NFT Score of B3. The 95% confidence intervals (CI) provided for specificity and sensitivity were based on the Wilson score method. The hypothesis tested was that majority read results had the lower bound of the 2-sided 95% CI greater than or equal to 55% for both sensitivity and specificity. | at autopsy within 9 months of baseline scan | 
| Flortaucipir Diagnostic Performance (NIA-AA Autopsy Diagnosis) | Sensitivity and specificity of majority interpretation of of AD pattern tau PET scan corresponding to NIA-AA autopsy diagnosis. The 95% CIs provided for specificity and sensitivity were based on the Wilson score method. The hypothesis tested was that majority read results had the lower bound of the 2-sided 95% CI greater than or equal to 55% for both sensitivity and specificity. | at autopsy within 9 months of baseline scan | 
| Inter-Reader Agreement | Fleiss' Kappa statistics were used to assess inter-reader agreement for the diagnostic decisions associated with primary outcome 1. Fleiss' kappa is a statistical measure for assessing the reliability of agreement between a fixed number of raters when assigning categorical ratings to a number of items or classifying items. Fleiss' kappa can range from 0 to 1 with 1 indicating perfect agreement between the readers. Results are reported as overall agreement, calculated as proportion of scans where reader pairs agreed, divided by the total number of scans read by each reader pair. | baseline scan |