Analysis of 18F-AV-1451 PET Imaging in Cognitively Healthy, MCI, and AD Subjects

An Open Label, Multicenter Study, Evaluating the Safety and Imaging Characteristics of 18F-AV-1451 in Cognitively Healthy Volunteers, Subjects With Mild Cognitive Impairment, and Subjects With Alzheimer's Disease

A Phase 2/3 cross-sectional and longitudinal observational study evaluating imaging characteristics of flortaucipir in control subjects and patients with clinically defined MCI and AD dementia (AD).

This study was conducted in 2 phases: a Phase 2 Exploratory Phase and a Phase 3 Confirmatory Phase. An overarching goal of the Exploratory Phase of this protocol was to further investigate the pattern of flortaucipir PET imaging across the disease course, in cognitively healthy subjects through patients with cognitive decline. To accomplish this goal, the protocol investigated flortaucipir results in younger and older cognitively healthy normal volunteers and patients with clinical diagnoses for cognitive complaints, ranging from MCI to mild and moderate AD dementia. Additionally, the Exploratory Phase of this protocol investigated relationships between flortaucipir PET signal and cognitive decline over the 18-month study period.

The second, Confirmatory Phase of the study was designed to provide independent validation of the relationships observed in the exploratory analyses of the first phase. In particular, the goal of the second phase was to confirm the relationship between flortaucipir uptake in the brain as measured by PET signals at baseline and the subsequent rate of cognitive decline observed over the 18-month longitudinal follow up.

Inclusion Criteria:

Exploratory Cognitively Healthy Subjects

• ≥ 20 to ≤ 40 years of age OR ≥ 50 years of age
• Mini-mental state examination (MMSE) ≥ 29
• No significant history of cognitive impairment

Exploratory MCI Subjects

• ≥ 50 years of age
• MMSE ≥ 24
• Have MCI consistent with National Institute on Aging-Alzheimer's Association (NIA-AA) working group's diagnostic guidelines for AD
• Have a study partner that can report on subject's activities of daily living

Exploratory AD Subjects

• ≥ 50 years of age
• MMSE > 10
• Have possible or probable AD based on the NIA-AA working group's diagnostic guidelines for AD
• Have a study partner that can report on subject's activities of daily living

Confirmatory Subjects

• ≥ 50 years of age
• MMSE ≥ 20 and ≤ 27
• Cognitively impaired subjects with either MCI or dementia with a suspected neurodegenerative cause
• Have a study partner that can report on subject's activities of daily living

Exclusion Criteria:

• Current clinically significant psychiatric disease
• Evidence of structural brain abnormalities
• History of moderate or severe traumatic brain injury
• Current clinically significant cardiovascular disease or ECG abnormalities, or additional risk factors for Torsades de Pointes
• Current clinically significant infectious disease, endocrine or metabolic disease, pulmonary, renal or hepatic impairment, or cancer
• History of alcohol or substance abuse or dependence
• 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.