Flortaucipir PET Imaging in the Preclinical, Prodromal and Dementia Phases of Alzheimer's Disease

Study Overview
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Brief Summary
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A Phase 1 study designed to evaluate imaging characteristics of flortaucipir in the preclinical, prodromal and dementia phases of Alzheimer's disease.

Detailed Description
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The Australian Imaging Biomarkers and Lifestyle Study (AIBL) is a multicenter multidisciplinary study of Alzheimer's disease and aging funded by the Commonwealth Scientific and Industrial Research Organisation (CSIRO) Flagship Initiative, involving research centers in both Victoria and Western Australia. The goal of the A08 protocol was to further investigate the positron emission tomography (PET) imaging results with flortaucipir in patients across the AD spectrum from individuals with subjective memory complaints (SMC) to those with dementia, based on recruitment into the parent AIBL study.

Official Title
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18F-AV-1451 PET Imaging in the Preclinical, Prodromal and Dementia Phases of Alzheimer's Disease

Conditions
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Alzheimer Disease, Mild Cognitive Impairment

Intervention / Treatment
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* Drug: Flortaucipir F18
* Procedure: Brain PET scan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet all inclusion criteria for the AIBL study protocol, with amyloid PET conducted or planned and MRI available Subjects in the MCI and AD groups required to have a reliable caregiver capable of providing information about the subjects' symptoms Exclusion Criteria: lifetime history of schizophrenia, schizoaffective disorder, or bipolar disorder history of electroconvulsive therapy MRI contraindicated claustrophobic or, otherwise, unable to tolerate the imaging procedure current clinically significant cardiovascular disease or clinically significant abnormalities on screening electrocardiogram history of additional risk factors for Torsades de Pointes current clinically significant infectious disease, endocrine or metabolic disease, or pulmonary, renal, or hepatic impairment that the investigator believes would affect study participation history of cancer (other than skin or in situ prostate cancer) within the previous 5 years current drug or alcohol abuse/dependence history of alcohol abuse/dependence with 2 years of the onset of the symptoms of dementia females of childbearing potential who were not surgically sterile, not refraining from sexual activity, or not using reliable methods of contraception

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alzheimer's disease (AD)<br>Alzheimer's disease subjects receiving a flortaucipir PET scan at baseline and 12 months | Drug: Flortaucipir F18<br>* IV injection, 240 megabecquerel (MBq) (6.5 mCi)<br>* Other names: Tauvid;Procedure: Brain PET scan<br>* positron emission tomography (PET) scan of the brain<br>|
| Experimental: Mild cognitive impairment (MCI)<br>Mild cognitive impairment subjects receiving a flortaucipir PET scan at baseline and 12 months | Drug: Flortaucipir F18<br>* IV injection, 240 megabecquerel (MBq) (6.5 mCi)<br>* Other names: Tauvid;Procedure: Brain PET scan<br>* positron emission tomography (PET) scan of the brain<br>|
| Experimental: Subjective memory complainers (SMC)<br>Subjective memory complainers receiving a flortaucipir PET scan at baseline and 12 months | Drug: Flortaucipir F18<br>* IV injection, 240 megabecquerel (MBq) (6.5 mCi)<br>* Other names: Tauvid;Procedure: Brain PET scan<br>* positron emission tomography (PET) scan of the brain<br>|
| Experimental: Cognitively normal (CN)<br>Cognitively normal subjects receiving a flortaucipir PET scan at baseline and 12 months | Drug: Flortaucipir F18<br>* IV injection, 240 megabecquerel (MBq) (6.5 mCi)<br>* Other names: Tauvid;Procedure: Brain PET scan<br>* positron emission tomography (PET) scan of the brain<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Flortaucipir PET Imaging (Quantitative) | Flortaucipir PET cortical weighted average standardized uptake value ratio (SUVr). For SUVr, a value of 1 signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain. | baseline scan | 
| Number of Participants With Advanced AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Scans were visually read independently by two expert readers at the sponsor, blinded to any clinical information. Subject scans were categorized as follows: Advanced AD Scan Pattern (τAD++), Moderate AD Scan Pattern (τAD+), Not AD Scan Pattern (τAD-). For this analysis, subjects with Advanced (τAD++) scans were analyzed vs. the combined Moderate and Not AD pattern groups (τAD+/τAD-). Amyloid status was obtained by florbetapir or carbon-11-labeled Pittsburgh compound B ([C-11] PiB) PET results available from the parent AIBL study. | baseline scan | 
| Number of Participants With AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Scans were visually read independently by two expert readers at the sponsor, blinded to any clinical information. Subject scans were categorized as follows: Advanced AD Scan Pattern (τAD++), Moderate AD Scan Pattern (τAD+), Not AD Scan Pattern (τAD-). For this analysis, subjects with AD Pattern scans (Advanced [τAD++] and Moderate [τAD+] Scan Pattern) were combined vs. the Not AD pattern group (τAD-). Amyloid status was obtained by florbetapir or carbon-11-labeled Pittsburgh compound B ([C-11] PiB) PET results available from the parent AIBL study. | baseline scan |