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

Alzheimer's Disease Clinical Trial

— MCI  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02016560
• Other study ID #: 18F-AV-1451-A05
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: December 2013
• Est. completion date: July 28, 2017

Study information

• Verified date: September 2020
• Source: Avid Radiopharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 383
• Est. completion date: July 28, 2017
• Est. primary completion date: July 28, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• florbetapir F 18

• Flortaucipir F18

Procedure:
• Brain PET Scan
positron emission tomography (PET) scan of the brain

Locations

Country	Name	City	State
United States	Boston University	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Quantum Laboratories	Deerfield Beach	Florida
United States	Duke University Medical Center	Durham	North Carolina
United States	21st Century Oncology	Fort Myers	Florida
United States	UC Irvine	Irvine	California
United States	Las Vegas Radiology	Las Vegas	Nevada
United States	Molecular NeuroImaging	New Haven	Connecticut
United States	Center for Brain Health - NYU Langone Medical Center	New York	New York
United States	Hoag Memorial	Newport Beach	California
United States	Sandlake Imaging	Orlando	Florida
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Banner Alzheimer's Institute	Phoenix	Arizona
United States	Butler Hospital	Providence	Rhode Island
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Alzheimer's Disease Center	Quincy	Massachusetts
United States	Norther California PET Imaging Center	Sacramento	California
United States	UC Davis	Sacramento	California
United States	Center for Clinical Imaging Research	Saint Louis	Missouri
United States	Meridien Research	Saint Petersburg	Florida
United States	UC San Francisco	San Francisco	California
United States	Neurological Research Institute	Santa Monica	California
United States	Four Peaks Neurology	Scottsdale	Arizona
United States	Mayo Clinic	Scottsdale	Arizona
United States	Banner Sun Health Research Institute	Sun City	Arizona
United States	USF Health Byrd Alzheimer's Center	Tampa	Florida
United States	Independent Imaging	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Avid Radiopharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confirmatory Phase: Relationship Between Neocortical Flortaucipir Uptake and the Subsequent Rate of Cognitive Decline	Confirm the relationship between neocortical flortaucipir uptake and the subsequent rate of cognitive decline at longitudinal follow up that was observed in the Exploratory Phase of the study. Patients were assigned to groups by majority classification of the flortaucipir positron emission tomography (PET) scan by five independent imaging physicians. Clinically meaningful cognitive and functional deterioration was defined as a 1 point or greater worsening on clinical dementia rating - sum of boxes (CDR-SB) score over the follow-up period.	between baseline and 18 months
Primary	Exploratory Phase: Cross-sectional Flortaucipir Imaging Results	Flortaucipir standardized uptake value ratio (SUVr). A value of 1 signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain.	baseline scan
Primary	Exploratory Phase: Longitudinal Change in Tau Deposition Over Time, by Amyloid Status	Assess the rate of change of tau deposition as measured by flortaucipir uptake (SUVr) over time. Change = 18 months SUVr - baseline SUVr.	baseline and 18 months
Secondary	Confirmatory Phase: Diagnostic Performance of Flortaucipir Visual Read	This analysis used dichotomized CDR-SB change as a truth standard (1 point or more worsening = true positive vs. less than 1 point worsening = true negative) to assess the diagnostic performance of baseline Advanced AD tau status (tAD++) as determined by flortaucipir scan interpretation. Sensitivity and Specificity were calculated for each of the 5 independent imaging readers. Sensitivity is the percentage of true positive cases correctly identified by an Advanced AD pattern scan. Specificity is the percentage of true negative cases correctly identified by scans that were not classified as Advanced AD pattern.	baseline and 18 months
Secondary	Exploratory Phase: Correlation Between Flortaucipir SUVr and Age	Flortaucipir standardized uptake value ratio (SUVr). A value of 1 signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain.	baseline scan