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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02516046




Registration number
NCT02516046
Ethics application status
Date submitted
3/08/2015
Date registered
5/08/2015
Date last updated
7/09/2020

Titles & IDs
Public title
18F-AV-1451 Autopsy Study
Scientific title
A Clinico-Pathological Study of the Correspondence Between 18F-AV-1451 PET Imaging and Post-Mortem Assessment of Tau Pathology
Secondary ID [1] 0 0
18F-AV-1451-A16
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Flortaucipir F18
Treatment: Surgery - PET Scan

Experimental: Flortaucipir PET Scan -


Treatment: Drugs: Flortaucipir F18
370 megabecquerel (MBq) IV single-dose

Treatment: Surgery: PET Scan
positron emission tomography (PET) scan

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
at autopsy within 9 months of baseline scan
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
at autopsy within 9 months of baseline scan
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
at autopsy within 9 months of baseline scan
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
at autopsy within 9 months of baseline scan
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
baseline scan

Eligibility
Key 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
Minimum age
50 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Diagnosis
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
University of Melbourne - Parkville
Recruitment postcode(s) [1] 0 0
3010 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Nevada
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Oklahoma
Country [11] 0 0
United States of America
State/province [11] 0 0
Rhode Island
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Avid Radiopharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02516046
Trial related presentations / publications
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Chief Medical Officer
Address 0 0
Avid Radiopharmaceuticals, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications