Clinical trial NCT02016560: Analysis of 18F-AV-1451 PET Imaging in Cognitively Healthy, MCI, and AD Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Alzheimer's Disease
Lead sponsor: Avid Radiopharmaceuticals
Sponsor class: INDUSTRY
First posted: 2013-12-20
Enrollment: 383
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: All subjects in both the exploratory and confirmatory phases of the study, receive both florbetapir and florbetapir scans, regardless of subgroup assignment.
Primary purpose: DIAGNOSTIC

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Confirmatory Phase: Relationship Between Neocortical Flortaucipir Uptake and the Subsequent Rate of Cognitive Decline
timeFrame: between baseline and 18 months
measure: Exploratory Phase: Cross-sectional Flortaucipir Imaging Results
timeFrame: baseline scan
measure: Exploratory Phase: Longitudinal Change in Tau Deposition Over Time, by Amyloid Status
timeFrame: baseline and 18 months
Secondary outcomes:
measure: Confirmatory Phase: Diagnostic Performance of Flortaucipir Visual Read
timeFrame: baseline and 18 months
measure: Exploratory Phase: Correlation Between Flortaucipir SUVr and Age
timeFrame: baseline scan
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner Alzheimer's Institute
state: Arizona
city: Scottsdale
country: United States
facility: Four Peaks Neurology
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Sun City
country: United States
facility: Banner Sun Health Research Institute
state: Arizona
city: Irvine
country: United States
facility: UC Irvine
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial
state: California
city: Sacramento
country: United States
facility: Norther California PET Imaging Center
state: California
city: Sacramento
country: United States
facility: UC Davis
state: California
city: San Francisco
country: United States
facility: UC San Francisco
state: California
city: Santa Monica
country: United States
facility: Neurological Research Institute
state: California
city: New Haven
country: United States
facility: Molecular NeuroImaging
state: Connecticut
city: Deerfield Beach
country: United States
facility: Quantum Laboratories
state: Florida
city: Fort Myers
country: United States
facility: 21st Century Oncology
state: Florida
city: Orlando
country: United States
facility: Sandlake Imaging
state: Florida
city: Saint Petersburg
country: United States
facility: Meridien Research
state: Florida
city: Tampa
country: United States
facility: USF Health Byrd Alzheimer's Center
state: Florida
city: West Palm Beach
country: United States
facility: Independent Imaging
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University
state: Massachusetts
city: Quincy
country: United States
facility: Alzheimer's Disease Center
state: Massachusetts
city: Saint Louis
country: United States
facility: Center for Clinical Imaging Research
state: Missouri
city: Las Vegas
country: United States
facility: Las Vegas Radiology
state: Nevada
city: New York
country: United States
facility: Center for Brain Health - NYU Langone Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Providence
country: United States
facility: Butler Hospital
state: Rhode Island
Study officials:
References:
citation: Lu M, Pontecorvo MJ, Devous MD Sr, Arora AK, Galante N, McGeehan A, Devadanam C, Salloway SP, Doraiswamy PM, Curtis C, Truocchio SP, Flitter M, Locascio T, Devine M, Zimmer JA, Fleisher AS, Mintun MA; AVID Collaborators. Aggregated Tau Measured by Visual Interpretation of Flortaucipir Positron Emission Tomography and the Associated Risk of Clinical Progression of Mild Cognitive Impairment and Alzheimer Disease: Results From 2 Phase III Clinical Trials. JAMA Neurol. 2021 Apr 1;78(4):445-453. doi: 10.1001/jamaneurol.2020.5505.