Tau Imaging in Subjects With Progressive Supranuclear Palsy, Corticobasal Degeneration and Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
This study will evaluate flortaucipir for brain imaging of tau in subjects with progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and healthy volunteers.

Official Title
-----------------
18F-AV-1451 Injection for Brain Imaging of Tau in Subjects With Progressive Supranuclear Palsy (PSP), Subjects With Corticobasal Degeneration (CBD) and Healthy Volunteers

Conditions
-----------------
Progressive Supranuclear Palsy, Corticobasal Degeneration

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Cognitively Healthy Volunteers Mini-mental state examination (MMSE) ≥ 28 No history of cognitive decline or parkinsonian motor disorder CBD and PSP subjects Able to walk 10 steps with minimal assistance MMSE ≥ 14 and ≤ 30 Subject has a reliable study partner who agrees to accompany subject to visits and spends at least 5 hours per week with the subject PSP subjects only Meet National Institute of Neurological Disorders and Stroke - Society for Progressive Supranuclear Palsy (NINDS-SPSP) probable or possible PSP criteria as modified for the Neuroprotection and Natural History Parkinson Plus Syndromes (NNIPPS) clinical trial CBD subjects only Meets 2013 consensus criteria for possible or probable corticobasal degeneration, corticobasal syndrome (CBS) subtype Exclusion Criteria: All subjects Have evidence of structural abnormalities such as vascular disease, large strokes or severe white matter disease or other mass lesion on screening MRI Claustrophobia Current clinically significant cardiovascular disease or clinically significant abnormalities on screening electrocardiogram (e.g. corrected QT interval >450 msec) Have a history of risk factors for Torsades de Pointes (e.g. heart failure, hypokalemia, family history of long QT syndrome) Have a current clinically significant infectious disease, endocrine or metabolic disease, pulmonary, renal or hepatic impairment, or cancer Females of childbearing potential who are not surgically sterile, not refraining from sexual activity or not using reliable methods of contraception Have received or participated in a trial with investigational medications in the past 30 days Have had a non-study related radiopharmaceutical imaging or treatment procedure within 7 days prior to the study imaging session Have a history of neuroleptic use for a prolonged period of time or within the past 6 months PSP and CBD subjects Have evidence of amyloid deposition Meet National Institute on Aging-Alzheimer's Association criteria for probable Alzheimer's Disease Have any other neurological condition other than CBS or PSP that could account for cognitive or motor deficits Serum or plasma progranulin level less than one standard deviation below the normal subject mean for the laboratory performing the assay Have a high-risk family history suggestive of tar DNA binding protein (TDP)-43 pathology or known mutations

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

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: PSP Subjects<br>Amyloid negative subjects with PSP receiving a flortaucipir PET scan at baseline and at 9 months. | Drug: Flortaucipir F18<br>* IV injection, 370 megabecquerel (MBq) (10 mCi)<br>* Other names: Tauvid;Procedure: Brain PET scan<br>* positron emission tomography (PET) scan of the brain 75-105 minutes post-injection<br>|
| Experimental: CBD subjects<br>Amyloid negative subjects with CBD receiving a flortaucipir PET scan at baseline and at 9 months. | Drug: Flortaucipir F18<br>* IV injection, 370 megabecquerel (MBq) (10 mCi)<br>* Other names: Tauvid;Procedure: Brain PET scan<br>* positron emission tomography (PET) scan of the brain 75-105 minutes post-injection<br>|
| Experimental: Healthy volunteers<br>Healthy volunteers receiving a flortaucipir PET scan at baseline. | Drug: Flortaucipir F18<br>* IV injection, 370 megabecquerel (MBq) (10 mCi)<br>* Other names: Tauvid;Procedure: Brain PET scan<br>* positron emission tomography (PET) scan of the brain 75-105 minutes post-injection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Flortaucipir Imaging in PSP, CBD and Healthy Volunteers | A PSP/CBD (PSP = progressive supranuclear palsy; CBD = corticobasal degeneration) targeted composite Standardized Uptake Value ratio (SUVr) was calculated as the voxel-weighted average from the regional SUVr values of the left, right, and total globus pallidus and the dentate nuclei of the cerebellum for both the baseline and 9 month PET scans. Additionally, a global cortical Alzheimer's Disease (AD)-targeted cortical SUVr was calculated. For SUVr, a value of 1 signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain. | baseline and 9 month scans |