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

Primary Purpose

Alzheimer's Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
florbetapir F 18
Flortaucipir F18
Brain PET Scan
Sponsored by
Avid Radiopharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Alzheimer's Disease

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Banner Alzheimer's Institute
  • Four Peaks Neurology
  • Mayo Clinic
  • Banner Sun Health Research Institute
  • UC Irvine
  • Hoag Memorial
  • Norther California PET Imaging Center
  • UC Davis
  • UC San Francisco
  • Neurological Research Institute
  • Molecular NeuroImaging
  • Quantum Laboratories
  • 21st Century Oncology
  • Sandlake Imaging
  • Meridien Research
  • USF Health Byrd Alzheimer's Center
  • Independent Imaging
  • Massachusetts General Hospital
  • Boston University
  • Alzheimer's Disease Center
  • Center for Clinical Imaging Research
  • Las Vegas Radiology
  • Center for Brain Health - NYU Langone Medical Center
  • Duke University Medical Center
  • University of Pennsylvania
  • Rhode Island Hospital
  • Butler Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Exploratory Cognitively Healthy Subjects

Exploratory MCI Subjects

Exploratory AD Subjects

Confirmatory Subjects

Arm Description

Subjects will receive an IV injection, 370 megabecquerel (MBq) (10 millicurie [mCi]), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline.

Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline, 9 months and 18 months.

Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline, 9 months and 18 months.

Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 and flortaucipir at baseline.

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

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 (τAD++) 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.
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.

Full Information

First Posted
December 16, 2013
Last Updated
September 3, 2020
Sponsor
Avid Radiopharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02016560
Brief Title
Analysis of 18F-AV-1451 PET Imaging in Cognitively Healthy, MCI, and AD Subjects
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
December 2013 (Actual)
Primary Completion Date
July 28, 2017 (Actual)
Study Completion Date
July 28, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Avid Radiopharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 2, Phase 3
Interventional Study Model
Sequential Assignment
Model Description
All subjects in both the exploratory and confirmatory phases of the study, receive both florbetapir and florbetapir scans, regardless of subgroup assignment.
Masking
Outcomes Assessor
Masking Description
Applies only to confirmatory phase: the independent readers are blinded to all clinical information.
Allocation
Non-Randomized
Enrollment
383 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Exploratory Cognitively Healthy Subjects
Arm Type
Experimental
Arm Description
Subjects will receive an IV injection, 370 megabecquerel (MBq) (10 millicurie [mCi]), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline.
Arm Title
Exploratory MCI Subjects
Arm Type
Experimental
Arm Description
Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline, 9 months and 18 months.
Arm Title
Exploratory AD Subjects
Arm Type
Experimental
Arm Description
Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline, 9 months and 18 months.
Arm Title
Confirmatory Subjects
Arm Type
Experimental
Arm Description
Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 and flortaucipir at baseline.
Intervention Type
Drug
Intervention Name(s)
florbetapir F 18
Other Intervention Name(s)
Amyvid, 18F-AV-45
Intervention Type
Drug
Intervention Name(s)
Flortaucipir F18
Other Intervention Name(s)
T807, 18F-AV-1451
Intervention Type
Procedure
Intervention Name(s)
Brain PET Scan
Intervention Description
positron emission tomography (PET) scan of the brain
Primary Outcome Measure Information:
Title
Confirmatory Phase: Relationship Between Neocortical Flortaucipir Uptake and the Subsequent Rate of Cognitive Decline
Description
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.
Time Frame
between baseline and 18 months
Title
Exploratory Phase: Cross-sectional Flortaucipir Imaging Results
Description
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.
Time Frame
baseline scan
Title
Exploratory Phase: Longitudinal Change in Tau Deposition Over Time, by Amyloid Status
Description
Assess the rate of change of tau deposition as measured by flortaucipir uptake (SUVr) over time. Change = 18 months SUVr - baseline SUVr.
Time Frame
baseline and 18 months
Secondary Outcome Measure Information:
Title
Confirmatory Phase: Diagnostic Performance of Flortaucipir Visual Read
Description
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 (τAD++) 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.
Time Frame
baseline and 18 months
Title
Exploratory Phase: Correlation Between Flortaucipir SUVr and Age
Description
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.
Time Frame
baseline scan

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Facility Information:
Facility Name
Banner Alzheimer's Institute
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Facility Name
Four Peaks Neurology
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
Mayo Clinic
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Banner Sun Health Research Institute
City
Sun City
State/Province
Arizona
ZIP/Postal Code
85351
Country
United States
Facility Name
UC Irvine
City
Irvine
State/Province
California
ZIP/Postal Code
92697
Country
United States
Facility Name
Hoag Memorial
City
Newport Beach
State/Province
California
ZIP/Postal Code
92663
Country
United States
Facility Name
Norther California PET Imaging Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95816
Country
United States
Facility Name
UC Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
UC San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Neurological Research Institute
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Molecular NeuroImaging
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Quantum Laboratories
City
Deerfield Beach
State/Province
Florida
ZIP/Postal Code
33064
Country
United States
Facility Name
21st Century Oncology
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33912
Country
United States
Facility Name
Sandlake Imaging
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Meridien Research
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33709
Country
United States
Facility Name
USF Health Byrd Alzheimer's Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
Facility Name
Independent Imaging
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33407
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Boston University
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Alzheimer's Disease Center
City
Quincy
State/Province
Massachusetts
ZIP/Postal Code
02169
Country
United States
Facility Name
Center for Clinical Imaging Research
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Las Vegas Radiology
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89147
Country
United States
Facility Name
Center for Brain Health - NYU Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
Butler Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02906
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
33587110
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.
Results Reference
derived

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

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