Longitudinal Evaluation of [18F]GTP1 as a PET Radioligand for Imaging Tau in the Brain of Participants With Alzheimer's Disease Compared to Healthy Participants

Study Overview
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Brief Summary
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This is an open-label, longitudinal observational study evaluating the imaging characteristics of the tau positron-emission tomography (PET) radioligand [18F] Genentech Tau Probe 1 (GTP1) in the brain of participants with prodromal, mild, and moderate Alzheimer's disease (AD) compared to healthy participants. The overall goal of this protocol is to evaluate the longitudinal change in tau burden using [18F]GTP1, a tau targeted radiopharmaceutical.

Official Title
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Longitudinal Evaluation of [18F]GTP1 as a PET Radioligand for Imaging Tau in the Brain of Patients With Prodromal, Mild, and Moderate Alzheimer's Disease Compared to Healthy Volunteers

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: [18F]GTP1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For All Participants: - Availability of a study partner who, in the investigator's judgment, has frequent and sufficient contact with the participant and is able to provide accurate information regarding the participant's cognitive and functional abilities, agrees to accompany the participant and provide information at visits For Healthy Participants: Healthy with no clinically relevant finding on physical examination at screening and upon reporting for the Baseline [18F]GTP1 imaging visit Have no cognitive complaint Have a Clinical Dementia Rating Scale (CDR) global score = 0 Have a Mini-Mental State Examination (MMSE) score of 28-30 For Participants With a Diagnosis of AD: Participants with mild or moderate AD must meet National Institute on Aging - Alzheimer's Association (NIA-AA) core clinical criteria for probable AD dementia, with an amnestic presentation Participants with prodromal AD must meet NIA-AA core clinical criteria for mild cognitive impairment (MCI) Have screening [18F]florbetapir PET imaging demonstrating amyloid binding based on qualitative visual read A brain MRI consistent with a diagnosis of AD, with no evidence of non-AD disease to account for dementia or MRI exclusion criteria Medications taken for symptomatic treatment of AD must remain stable for at least 30 days prior to screening visit Satisfy one of the following subgroups: Approximately 20 prodromal AD (MMSE 24-30, CDR = 0.5); Approximately 20 mild AD (MMSE 22-30, CDR = 0.5 or 1); Approximately 20 moderate AD (MMSE 16-21, CDR = 0.5 or 1 or 2) Exclusion Criteria: Current or prior history of any drug or alcohol abuse Participants with any significant psychiatric, neurological, or unstable medical disorder expected to interfere with the study Participants unable to undergo MRI and PET scan For participants contributing CSF samples, any contraindication to lumbar puncture Prior participation in other research protocols or clinical care in the last year such a radiation exposure combined with that from the present study exceeds an effective dose of 50 millisievert (mSV), the allowable annual limit for research participants as stipulated by the Food and Drug Administration (FDA)

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [18F]GTP1<br>Participants will complete [18F]GTP1 PET imaging at four time points: Baseline, 6 months, 12 months and 18 months. For each [18F]GTP1 imaging session, the following procedure will be performed: a catheter will be placed for intravenous (IV) administration of [18F]GTP1. Participants will receive an IV bolus injection of up to 370 megabecquerel (MBq) (10 millicurie [mCi]) of [18F]GTP1. | Drug: [18F]GTP1<br>* Participants will receive [18F]GTP1 as per the schedule specified in the arm description.<br>* Other names: [18F]RO6880276;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Standardized Uptake Value Ratio (SUVR) as Measured by [18F]GTP1 |  | From Baseline to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation Coefficient Between Change in SUVR (as Measured by [18F]GTP1) and Change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)13 |  | From Baseline to 18 months | 
| Correlation Coefficient Between Change in SUVR (as Measured by [18F]GTP1) and Change in Volumetric Magnetic Resonance Imaging (MRI) Measures |  | From Baseline to 18 months | 
| Correlation Coefficient Between Change in SUVR (as Measured by [18F]GTP1) and Change in Cerebrospinal Fluid (CSF) Markers |  | From Baseline to 18 months | 
| Percentage of Participants With Adverse Events (AEs) |  | From Baseline to 18 months | 
| Test-Retest Variability Based on [18F]GTP1 PET Scans |  | From date of test scan to 7-21 days after test scan |