18F-AV-1451 Autopsy Study

NCT02516046 | Completed Phase 3 Results DMC

• 1 other identifier: 18F-AV-1451-A16
• Study Type: interventional
• Target: 156
• Locations: 2 countries
• Sites: 31

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.

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (2)

• 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.

  at autopsy within 9 months of baseline scan

• 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.

  at autopsy within 9 months of baseline scan

Secondary Outcomes (3)

• Flortaucipir Diagnostic Performance (NFT Score)

  at autopsy within 9 months of baseline scan

• Flortaucipir Diagnostic Performance (NIA-AA Autopsy Diagnosis)

  at autopsy within 9 months of baseline scan

• Inter-Reader Agreement

  baseline scan

Other Outcomes (1)

• Diagnostic Performance of Individual Readers (NFT Score B2-B3 as Truth Positive)

  at autopsy within 9 months of baseline scan

Study Arms (1)

Flortaucipir PET Scan

EXPERIMENTAL

Drug: Flortaucipir F18; Procedure: PET Scan

Interventions

Flortaucipir F18 DRUG

370 megabecquerel (MBq) IV single-dose

Also known as: [F-18]T807, 18F-AV-1451, LY3191748

Flortaucipir PET Scan

PET Scan PROCEDURE

positron emission tomography (PET) scan

Flortaucipir PET Scan

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Avid Radiopharmaceuticals: lead

Study Sites (31)

Banner Alzheimer's Institute

Phoenix, Arizona, 85006, United States

Location

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

Cherlin Research

Los Gatos, California, 95032, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92658, United States

Location

California Research Foundation

San Diego, California, 92103, United States

Location

Pacific Research Network

San Diego, California, 92103, United States

Location

Ray Dolby Brain Health Center

San Francisco, California, 94114, United States

Location

Syrentis Clinical Research

Santa Ana, California, 92705, United States

Location

Neuropsychiatric Research Center of Southwest Florida

Fort Myers, Florida, 33912, United States

Location

Galiz Research

Hialeah, Florida, 33016, United States

Location

Merritt Island Medical Research

Merritt Island, Florida, 32952, United States

Location

Miami Jewish Health Systems

Miami, Florida, 33137, United States

Location

D de la Vega MD Research Group

Miami, Florida, 33185, United States

Location

Bioclinica

Orlando, Florida, 32806, United States

Location

Emory University Brain Health Center

Atlanta, Georgia, 30329, United States

Location

Alzheimer's Disease Center

Quincy, Massachusetts, 02169, United States

Location

Steinberg Diagnostics

Henderson, Nevada, 89052, United States

Location

Adirondack Medical Research Center

Glens Falls, New York, 12801, United States

Location

Clarity Clinical Research, LLC

Syracuse, New York, 13210, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

Valley Medical Primary Care

Centerville, Ohio, 45459, United States

Location

Hospice of the Western Reserve

Cleveland, Ohio, 44119, United States

Location

American Clinical Trials, LLC (Site 1216)

Oklahoma City, Oklahoma, 73112, United States

Location

Oklahoma Behavioral Health

Oklahoma City, Oklahoma, 73112, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Houston Methodist Research Institute

Houston, Texas, 77030, United States

Location

Sante Clinical Research

Kerrville, Texas, 78028, United States

Location

Overlake Internal Medicine Associates, PS

Bellevue, Washington, 98004, United States

Location

University of Washington Medicine

Seattle, Washington, 98104, United States

Location

University of Melbourne

Parkville, Victoria, 3010, Australia

Location

Related Publications (4)

• 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.

  PMID: 22265587 BACKGROUND

• 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.

  PMID: 22101365 BACKGROUND

• 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.

  PMID: 32338734 RESULT

• 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.

  PMID: 32542468 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Results Point of Contact

• Title: Medical Director
• Organization: Avid Radiopharmaceuticals, Inc.

clinicaloperations@avidrp.com

215-298-0700

Study Officials

• Chief Medical Officer

  Avid Radiopharmaceuticals, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2015
• First Posted: August 5, 2015
• Study Start: September 1, 2015
• Primary Completion: June 13, 2018
• Study Completion: July 15, 2018
• Last Updated: September 7, 2020
• Results First Posted: September 7, 2020

Record last verified: 2020-09

Locations

AU (1); US (30)