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

Phase 1

Completed

• Conditions: Alzheimer Disease; Mild Cognitive Impairment
• Interventions: Drug: Flortaucipir F18; Procedure: Brain PET scan

• Registration Number: NCT04468347
• Lead Sponsor: Avid Radiopharmaceuticals

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study Start: 2014-10
• Primary Completion: 2018-02
• Study Completion: 2018-02
• Study First Submitted: 2020-07-08
• Study First Submitted QC: 2020-07-08
• Study First Posted: 2020-07-13
• Results First Submitted: 2020-07-27
• Status Verified: 2020-09
• Results First Submitted QC: 2020-09-03
• Last Update Submitted: 2020-09-03
• Results First Posted: 2020-09-25
• Last Update Posted: 2020-09-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 89

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mild cognitive impairment (MCI)	Brain PET scan	Mild cognitive impairment subjects receiving a flortaucipir PET scan at baseline and 12 months
Alzheimer's disease (AD)	Brain PET scan	Alzheimer's disease subjects receiving a flortaucipir PET scan at baseline and 12 months
Subjective memory complainers (SMC)	Brain PET scan	Subjective memory complainers receiving a flortaucipir PET scan at baseline and 12 months
Cognitively normal (CN)	Brain PET scan	Cognitively normal subjects receiving a flortaucipir PET scan at baseline and 12 months
Alzheimer's disease (AD)	Flortaucipir F18	Alzheimer's disease subjects receiving a flortaucipir PET scan at baseline and 12 months
Subjective memory complainers (SMC)	Flortaucipir F18	Subjective memory complainers receiving a flortaucipir PET scan at baseline and 12 months
Cognitively normal (CN)	Flortaucipir F18	Cognitively normal subjects receiving a flortaucipir PET scan at baseline and 12 months
Mild cognitive impairment (MCI)	Flortaucipir F18	Mild cognitive impairment subjects receiving a flortaucipir PET scan at baseline and 12 months

Primary Outcome Measures

Name	Time	Method
Number of Participants With AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status	baseline scan	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.
Number of Participants With Advanced AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status	baseline scan	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.
Flortaucipir PET Imaging (Quantitative)	baseline scan	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.