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18F-AV-1451 Autopsy Study

Primary Purpose

Alzheimer's Disease

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Flortaucipir F18
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

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Have a projected life expectancy of ≤ 6 months
  • Can tolerate a 20 minute PET scan
  • Give informed consent or have a legally authorized representative to consent for study procedures and brain donation consistent with the legal requirements of the State in which they die

Exclusion Criteria:

  • Aggressively being treated with life sustaining measures
  • Known to have a structural brain lesion that would interfere either with PET imaging or pathological assessment
  • Clinically significant infectious disease
  • Currently receiving any investigational medications except with permission from the study sponsor
  • Participated in an experimental study with an amyloid or tau targeting agent
  • Suspected encephalopathy due to alcoholism or end-stage liver disease
  • Females of childbearing potential
  • History of risk factors for Torsades de Pointes or are currently taking medication known to cause QT prolongation

Sites / Locations

  • Banner Alzheimer's Institute
  • St. Joseph's Hospital and Medical Center
  • Cherlin Research
  • Hoag Memorial Hospital Presbyterian
  • California Research Foundation
  • Pacific Research Network
  • Ray Dolby Brain Health Center
  • Syrentis Clinical Research
  • Neuropsychiatric Research Center of Southwest Florida
  • Galiz Research
  • Merritt Island Medical Research
  • Miami Jewish Health Systems
  • D de la Vega MD Research Group
  • Bioclinica
  • Emory University Brain Health Center
  • Alzheimer's Disease Center
  • Steinberg Diagnostics
  • Adirondack Medical Research Center
  • Clarity Clinical Research, LLC
  • Duke University Medical Center
  • Wake Forest School of Medicine
  • Valley Medical Primary Care
  • Hospice of the Western Reserve
  • American Clinical Trials, LLC (Site 1216)
  • Oklahoma Behavioral Health
  • Rhode Island Hospital
  • Houston Methodist Research Institute
  • Sante Clinical Research
  • Overlake Internal Medicine Associates, PS
  • University of Washington Medicine
  • University of Melbourne

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Flortaucipir PET Scan

Arm Description

Outcomes

Primary Outcome Measures

Primary Outcome 1: Diagnostic Performance of Individual Readers (NFT Score)
Sensitivity and specificity of 5 independent readers' interpretations of ante-mortem flortaucipir PET imaging for detection of a pattern of flortaucipir neocortical uptake that corresponds to neurofibrillary tangles (NFT) Score of B3 (Hyman et al., 2012; Montine et al., 2012). NFT B scores range from B0 (Braak Stage 0; no NFTs in the brain) to B3 (Braak Stage V/VI; widespread NFTs in the brain). Sensitivity and specificity are percentages that can range from 0 to 100%. The hypothesis tested was that, of the 5 independent imaging physicians, at least 3 will have the lower bounds of 2-sided 95% CIs ≥50%, for both sensitivity and specificity.
Primary Outcome 2: Diagnostic Performance of Individual Readers (NIA-AA Autopsy Diagnosis)
Sensitivity and specificity of 5 independent readers' interpretations of ante-mortem flortaucipir imaging for detection of a pattern of flortaucipir neocortical uptake that corresponds to high levels of Alzheimer's disease neuropathologic change (High ADNC) as defined by National Institute on Aging-Alzheimer's Association (NIA-AA) criteria. ADNC categories are None, Low, Intermediate and High, with High indicating the most severe level of AD-related pathology changes in the brain (Hyman et al., Alzheimers Dement. 2012 Jan;8(1):1-13). The hypothesis tested was that, of the 5 independent imaging physicians, at least 3 will have the lower bounds of 2-sided 95% CIs ≥50%, for both sensitivity and specificity.

Secondary Outcome Measures

Flortaucipir Diagnostic Performance (NFT Score)
Sensitivity and specificity of majority interpretation of AD pattern tau PET scan corresponding to NFT Score of B3. The 95% confidence intervals (CI) provided for specificity and sensitivity were based on the Wilson score method. The hypothesis tested was that majority read results had the lower bound of the 2-sided 95% CI greater than or equal to 55% for both sensitivity and specificity.
Flortaucipir Diagnostic Performance (NIA-AA Autopsy Diagnosis)
Sensitivity and specificity of majority interpretation of of AD pattern tau PET scan corresponding to NIA-AA autopsy diagnosis. The 95% CIs provided for specificity and sensitivity were based on the Wilson score method. The hypothesis tested was that majority read results had the lower bound of the 2-sided 95% CI greater than or equal to 55% for both sensitivity and specificity.
Inter-Reader Agreement
Fleiss' Kappa statistics were used to assess inter-reader agreement for the diagnostic decisions associated with primary outcome 1. Fleiss' kappa is a statistical measure for assessing the reliability of agreement between a fixed number of raters when assigning categorical ratings to a number of items or classifying items. Fleiss' kappa can range from 0 to 1 with 1 indicating perfect agreement between the readers. Results are reported as overall agreement, calculated as proportion of scans where reader pairs agreed, divided by the total number of scans read by each reader pair.

Full Information

First Posted
August 3, 2015
Last Updated
September 3, 2020
Sponsor
Avid Radiopharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02516046
Brief Title
18F-AV-1451 Autopsy Study
Official Title
A Clinico-Pathological Study of the Correspondence Between 18F-AV-1451 PET Imaging and Post-Mortem Assessment of Tau Pathology
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
September 2015 (undefined)
Primary Completion Date
June 13, 2018 (Actual)
Study Completion Date
July 15, 2018 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study is designed to test the relationship between ante-mortem flortaucipir Positron Emission Tomography (PET) imaging and tau neurofibrillary pathology associated with Alzheimer's disease (AD), as measured at autopsy.

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 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
156 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Flortaucipir PET Scan
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Flortaucipir F18
Other Intervention Name(s)
[F-18]T807, 18F-AV-1451, LY3191748
Intervention Description
370 megabecquerel (MBq) IV single-dose
Intervention Type
Procedure
Intervention Name(s)
PET Scan
Intervention Description
positron emission tomography (PET) scan
Primary Outcome Measure Information:
Title
Primary Outcome 1: Diagnostic Performance of Individual Readers (NFT Score)
Description
Sensitivity and specificity of 5 independent readers' interpretations of ante-mortem flortaucipir PET imaging for detection of a pattern of flortaucipir neocortical uptake that corresponds to neurofibrillary tangles (NFT) Score of B3 (Hyman et al., 2012; Montine et al., 2012). NFT B scores range from B0 (Braak Stage 0; no NFTs in the brain) to B3 (Braak Stage V/VI; widespread NFTs in the brain). Sensitivity and specificity are percentages that can range from 0 to 100%. The hypothesis tested was that, of the 5 independent imaging physicians, at least 3 will have the lower bounds of 2-sided 95% CIs ≥50%, for both sensitivity and specificity.
Time Frame
at autopsy within 9 months of baseline scan
Title
Primary Outcome 2: Diagnostic Performance of Individual Readers (NIA-AA Autopsy Diagnosis)
Description
Sensitivity and specificity of 5 independent readers' interpretations of ante-mortem flortaucipir imaging for detection of a pattern of flortaucipir neocortical uptake that corresponds to high levels of Alzheimer's disease neuropathologic change (High ADNC) as defined by National Institute on Aging-Alzheimer's Association (NIA-AA) criteria. ADNC categories are None, Low, Intermediate and High, with High indicating the most severe level of AD-related pathology changes in the brain (Hyman et al., Alzheimers Dement. 2012 Jan;8(1):1-13). The hypothesis tested was that, of the 5 independent imaging physicians, at least 3 will have the lower bounds of 2-sided 95% CIs ≥50%, for both sensitivity and specificity.
Time Frame
at autopsy within 9 months of baseline scan
Secondary Outcome Measure Information:
Title
Flortaucipir Diagnostic Performance (NFT Score)
Description
Sensitivity and specificity of majority interpretation of AD pattern tau PET scan corresponding to NFT Score of B3. The 95% confidence intervals (CI) provided for specificity and sensitivity were based on the Wilson score method. The hypothesis tested was that majority read results had the lower bound of the 2-sided 95% CI greater than or equal to 55% for both sensitivity and specificity.
Time Frame
at autopsy within 9 months of baseline scan
Title
Flortaucipir Diagnostic Performance (NIA-AA Autopsy Diagnosis)
Description
Sensitivity and specificity of majority interpretation of of AD pattern tau PET scan corresponding to NIA-AA autopsy diagnosis. The 95% CIs provided for specificity and sensitivity were based on the Wilson score method. The hypothesis tested was that majority read results had the lower bound of the 2-sided 95% CI greater than or equal to 55% for both sensitivity and specificity.
Time Frame
at autopsy within 9 months of baseline scan
Title
Inter-Reader Agreement
Description
Fleiss' Kappa statistics were used to assess inter-reader agreement for the diagnostic decisions associated with primary outcome 1. Fleiss' kappa is a statistical measure for assessing the reliability of agreement between a fixed number of raters when assigning categorical ratings to a number of items or classifying items. Fleiss' kappa can range from 0 to 1 with 1 indicating perfect agreement between the readers. Results are reported as overall agreement, calculated as proportion of scans where reader pairs agreed, divided by the total number of scans read by each reader pair.
Time Frame
baseline scan
Other Pre-specified Outcome Measures:
Title
Diagnostic Performance of Individual Readers (NFT Score B2-B3 as Truth Positive)
Description
Sensitivity and specificity of 5 independent readers' interpretations of ante-mortem flortaucipir PET imaging for detection of a pattern of flortaucipir neocortical uptake that corresponds to neurofibrillary tangles (NFT) Score of B3 (Hyman et al., 2012; Montine et al., 2012). NFT B scores range from B0 (no NFTs in the brain) to B3 (widespread NFTs in the brain). Sensitivity and specificity are percentages that can range from 0 to 100%. For this analysis, B scores of B2-B3 were considered truth positive, and B scores of B0-B1 were considered truth negative.
Time Frame
at autopsy within 9 months of baseline scan

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Have a projected life expectancy of ≤ 6 months Can tolerate a 20 minute PET scan Give informed consent or have a legally authorized representative to consent for study procedures and brain donation consistent with the legal requirements of the State in which they die Exclusion Criteria: Aggressively being treated with life sustaining measures Known to have a structural brain lesion that would interfere either with PET imaging or pathological assessment Clinically significant infectious disease Currently receiving any investigational medications except with permission from the study sponsor Participated in an experimental study with an amyloid or tau targeting agent Suspected encephalopathy due to alcoholism or end-stage liver disease Females of childbearing potential History of risk factors for Torsades de Pointes or are currently taking medication known to cause QT prolongation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chief Medical Officer
Organizational Affiliation
Avid Radiopharmaceuticals, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Banner Alzheimer's Institute
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Facility Name
St. Joseph's Hospital and Medical Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
Cherlin Research
City
Los Gatos
State/Province
California
ZIP/Postal Code
95032
Country
United States
Facility Name
Hoag Memorial Hospital Presbyterian
City
Newport Beach
State/Province
California
ZIP/Postal Code
92658
Country
United States
Facility Name
California Research Foundation
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Pacific Research Network
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Ray Dolby Brain Health Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94114
Country
United States
Facility Name
Syrentis Clinical Research
City
Santa Ana
State/Province
California
ZIP/Postal Code
92705
Country
United States
Facility Name
Neuropsychiatric Research Center of Southwest Florida
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33912
Country
United States
Facility Name
Galiz Research
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33016
Country
United States
Facility Name
Merritt Island Medical Research
City
Merritt Island
State/Province
Florida
ZIP/Postal Code
32952
Country
United States
Facility Name
Miami Jewish Health Systems
City
Miami
State/Province
Florida
ZIP/Postal Code
33137
Country
United States
Facility Name
D de la Vega MD Research Group
City
Miami
State/Province
Florida
ZIP/Postal Code
33185
Country
United States
Facility Name
Bioclinica
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Emory University Brain Health Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Facility Name
Alzheimer's Disease Center
City
Quincy
State/Province
Massachusetts
ZIP/Postal Code
02169
Country
United States
Facility Name
Steinberg Diagnostics
City
Henderson
State/Province
Nevada
ZIP/Postal Code
89052
Country
United States
Facility Name
Adirondack Medical Research Center
City
Glens Falls
State/Province
New York
ZIP/Postal Code
12801
Country
United States
Facility Name
Clarity Clinical Research, LLC
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Wake Forest School of Medicine
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Valley Medical Primary Care
City
Centerville
State/Province
Ohio
ZIP/Postal Code
45459
Country
United States
Facility Name
Hospice of the Western Reserve
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44119
Country
United States
Facility Name
American Clinical Trials, LLC (Site 1216)
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Facility Name
Oklahoma Behavioral Health
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
Houston Methodist Research Institute
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Sante Clinical Research
City
Kerrville
State/Province
Texas
ZIP/Postal Code
78028
Country
United States
Facility Name
Overlake Internal Medicine Associates, PS
City
Bellevue
State/Province
Washington
ZIP/Postal Code
98004
Country
United States
Facility Name
University of Washington Medicine
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
University of Melbourne
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3010
Country
Australia

12. IPD Sharing Statement

Citations:
PubMed Identifier
22265587
Citation
Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, Mirra SS, Nelson PT, Schneider JA, Thal DR, Thies B, Trojanowski JQ, Vinters HV, Montine TJ. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease. Alzheimers Dement. 2012 Jan;8(1):1-13. doi: 10.1016/j.jalz.2011.10.007.
Results Reference
background
PubMed Identifier
22101365
Citation
Montine TJ, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, Mirra SS, Nelson PT, Schneider JA, Thal DR, Trojanowski JQ, Vinters HV, Hyman BT; National Institute on Aging; Alzheimer's Association. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach. Acta Neuropathol. 2012 Jan;123(1):1-11. doi: 10.1007/s00401-011-0910-3. Epub 2011 Nov 20.
Results Reference
background
PubMed Identifier
32338734
Citation
Fleisher AS, Pontecorvo MJ, Devous MD Sr, Lu M, Arora AK, Truocchio SP, Aldea P, Flitter M, Locascio T, Devine M, Siderowf A, Beach TG, Montine TJ, Serrano GE, Curtis C, Perrin A, Salloway S, Daniel M, Wellman C, Joshi AD, Irwin DJ, Lowe VJ, Seeley WW, Ikonomovic MD, Masdeu JC, Kennedy I, Harris T, Navitsky M, Southekal S, Mintun MA; A16 Study Investigators. Positron Emission Tomography Imaging With [18F]flortaucipir and Postmortem Assessment of Alzheimer Disease Neuropathologic Changes. JAMA Neurol. 2020 Jul 1;77(7):829-839. doi: 10.1001/jamaneurol.2020.0528. Erratum In: JAMA Neurol. 2023 Aug 1;80(8):873.
Results Reference
result
PubMed Identifier
32542468
Citation
Pontecorvo MJ, Keene CD, Beach TG, Montine TJ, Arora AK, Devous MD Sr, Navitsky M, Kennedy I, Joshi AD, Lu M, Serrano GE, Sue LI, Intorcia AJ, Rose SE, Wilson A, Hellstern L, Coleman N, Flitter M, Aldea P, Fleisher AS, Mintun MA, Siderowf A. Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer's disease pathology: a clinicopathological study. EJNMMI Res. 2020 Jun 15;10(1):65. doi: 10.1186/s13550-020-00653-x.
Results Reference
derived

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18F-AV-1451 Autopsy Study

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