A Reader Study to Assess Accuracy and Reliability of Flortaucipir F 18 Positron Emission Tomography (PET) Scan Interpretation

NCT03901092 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 18F-AV-1451-FR01
• Study Type: interventional
• Target: 242
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the performance of physician readers trained to read flortaucipir-PET (positron emission tomography) scans.

Conditions

Alzheimer Disease

Keywords

flortaucipir F 18; Positron Emission Tomography; 18F-AV-1451; Diagnostic imaging; Tau imaging

Outcome Measures

Primary Outcomes (3)

• Primary Objective 1 Analysis 1: Diagnostic Performance of Individual Readers (NFT Score)

  Sensitivity and specificity of 5 independent readers' interpretations of ante-mortem 18F-AV-1451 PET imaging for detection of a pattern of 18F-AV-1451 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%. 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.

  baseline scan

• Primary Objective 1 Analysis 2: Diagnostic Performance of Individual Readers (NIA-AA Autopsy Diagnosis)

  Sensitivity and specificity of 5 independent readers' interpretations of ante-mortem 18F-AV-1451 PET imaging for detection of a pattern of 18F-AV-1451 neocortical uptake that corresponds to high levels of AD neuropathologic change (High ADNC) as defined by National Institute on Aging-Alzheimer's Association (NIA-AA) criteria (see Hyman et al. 2012). ADNC categories are None, Low, Intermediate and High, with High indicating the most severe level of AD-related pathology changes in the brain. 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.

  baseline scan

• Primary Objective 2: Inter-reader Reliability of Reader Interpretation of Flortaucipir-PET Imaging

  As measured by Fleiss' Kappa across all scans read. 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. Scan results binarized as positive AD pattern versus negative AD pattern. Results are displayed as percentage of agreement for individual reader pairs, computed as follows: number of images for which reader had the same interpretation divided by the total number of images evaluated, multiplied by 100%.

  baseline scan

Secondary Outcomes (5)

• Secondary Objective 1 Analysis 1: Diagnostic Performance of τAD++ Flortaucipir PET Images to Detect B3 NFTs

  baseline scan

• Secondary Objective 1 Analysis 2: Diagnostic Performance of τAD++ Flortaucipir PET Images to Detect High ADNC

  baseline scan

• Secondary Objective 2: Inter-reader Reliability of Reader Interpretation of τAD++ Flortaucipir PET Images

  baseline scan

• Secondary Objective 3: Inter-reader Reliability of Flortaucipir PET Scan Interpretation in the Population of Intended Use

  baseline scan

• Secondary Objective 4: Intra-reader Reliability of Reader Interpretation of Flortaucipir-PET Imaging

  baseline scan

Study Arms (1)

Flortaucipir PET Scan

EXPERIMENTAL

Scans previously acquired from Study A16 (NCT02516046) and A05 (NCT02016560) will be read by independent, blinded readers.

Drug: flortaucipir F 18

Interventions

flortaucipir F 18 DRUG

No study drug will be administered.

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

Flortaucipir PET Scan

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

Scan Reader Criteria (5 total): * Board-certified in radiology or nuclear medicine * Professional experience interpreting PET scans * Naive to study protocol * No previous training or exposure to Avid Flortaucipir F 18 read methodology Scan Criteria: \- Previous enrollment in Study A05 confirmatory cohort (NCT02016560), or A16 (NCT02516046) Scan Study Population Criteria for FR01 (A05 confirmatory cohort): * Cognitively-impaired * mild cognitive impairment (MCI) or dementia with suspected neurodegenerative cause * mini-mental status exam (MMSE) score of 20-27, inclusive Scan Study Population Criteria for FR01 (Study A16): * Subjects at end of life (less than or equal to 6 months) * Imaged with flortaucipir F18 and came to autopsy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Avid Radiopharmaceuticals: lead

Study Sites (1)

American College of Radiology

Philadelphia, Pennsylvania, 19103, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole

Condition Hierarchy (Ancestors)

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

Results Point of Contact

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

clinicaloperations@avidrp.com

215-298-0700

Study Officials

• Study Director

  Avid Radiopharmaceuticals

  STUDY DIRECTOR

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
• Masking Details: PET scans were obtained in an open-label fashion.
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Physician PET scan readers are participants, blinded to demographic and clinical data from the source PET scans.

Study Record Dates

• First Submitted: March 27, 2019
• First Posted: April 3, 2019
• Study Start: March 26, 2019
• Primary Completion: April 26, 2019
• Study Completion: April 26, 2019
• Last Updated: September 9, 2020
• Results First Posted: August 11, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)