Alzheimer DiseasePhase 3NCT03901092
A Reader Study to Assess Accuracy and Reliability of Flortaucipir F 18 Positron Emission Tomography (PET) Scan Interpretation
A Phase 3 study testing flortaucipir F 18 in people with Alzheimer Disease, run by Avid Radiopharmaceuticals at 1 site in United States.
Trial summary
This study will evaluate the performance of physician readers trained to read flortaucipir-PET (positron emission tomography) scans. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- flortaucipir F 18
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 242 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Mar 2019to 26 Apr 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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
Trial locations and contacts
1 site in 1 country.
United States1 site
American College of Radiology
Philadelphia, Pennsylvania, 19103
About this study
Official title: A Reader Study to Assess Accuracy and Reliability of Flortaucipir F 18 PET Scan Interpretation
This study will evaluate the performance of physician readers trained to read flortaucipir-PET (positron emission tomography) scans.
- Conditions
- Alzheimer Disease
- Being tested
- flortaucipir F 18
- Keywords
- flortaucipir F 18, Positron Emission Tomography, 18F-AV-1451, Diagnostic imaging, Tau imaging
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
flortaucipir F 18Drug
Also called 18F-AV-1451, [F-18]T807, LY3191748
No study drug will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Flortaucipir PET Scan | Experimental | Scans previously acquired from Study A16 (NCT02516046) and A05 (NCT02016560) will be read by independent, blinded readers. Receives: Drug: flortaucipir F 18 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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%.
Measured: baseline scan
Secondary outcomes (5)
Secondary Objective 1 Analysis 1: Diagnostic Performance of τAD++ Flortaucipir PET Images to Detect B3 NFTs
Flortaucipir F 18 PET imaging will be classified by each reader as either neocortical uptake not consistent with AD (τAD-), neocortical uptake consistent with AD (τAD+), or neocortical uptake consistent with AD with uptake beyond the temporal/occipital regions (τAD++). NFT scoring is according to Hyman, et al 2012. Truth positive is a NFT B3 score. Truth negative is NFT <B3 score.
Measured: baseline scan
Secondary Objective 1 Analysis 2: Diagnostic Performance of τAD++ Flortaucipir PET Images to Detect High ADNC
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 (Hyman et al. 2012). Truth positive is a High ADNC score. Truth negative is No/Low/Intermediate ADNC score.
Measured: baseline scan
Secondary Objective 2: Inter-reader Reliability of Reader Interpretation of τAD++ Flortaucipir PET Images
Overall reader agreement as measured by Fleiss' Kappa statistic. Scan results binarized as τAD++ versus τAD+/τAD-. 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%.
Measured: baseline scan
Secondary Objective 3: Inter-reader Reliability of Flortaucipir PET Scan Interpretation in the Population of Intended Use
Reader agreement measured by Fleiss' Kappa across scans from non-autopsy cases from Study A05. Scan results binarized as positive for AD pattern versus negative for 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%.
Measured: baseline scan
Secondary Objective 4: Intra-reader Reliability of Reader Interpretation of Flortaucipir-PET Imaging
Cohen's Kappa will be calculated for each of 5 readers to assess the intra-reader reliability of flortaucipir F 18 PET scan visual interpretation. The statistic takes into account the possibility of the agreement occurring by chance. Cohen's kappa values range from 0 to 1 with 1 representing perfect agreement. Results are displayed as percentage of agreement within a reader, computed as follows: number of images for which reader had the same interpretation at initial and second read divided by the total number of images evaluated twice by a reader, multiplied by 100%.
Measured: baseline scan
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2019
- Study start26 Mar 2019
- Primary completion26 Apr 2019
- Study completion26 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Physician PET scan readers are participants, blinded to demographic and clinical data from the source PET scans.
- Masking
- None (open label)
- Enrolment
- 242 participants (actual)
Sponsor and investigators
- Lead sponsor
- Avid Radiopharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Avid Radiopharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03901092
- Sponsor's protocol ID
- 18F-AV-1451-FR01
- Status last verified
- Aug 2020
- First submitted
- 27 Mar 2019
- Last updated
- 9 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Imabayashi E, Morris A, Iaccarino L, Arora AK, Kamiki E, Lu M. 18F-flortaucipir PET imaging: Biodistribution in the Japanese population and diagnostic accuracy by Japanese readers. Ann Nucl Med. 2026 Jul 17. doi: 10.1007/s12149-026-02239-4. Online ahead of print.
PubMed 42467182
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Reader Study to Assess Accuracy and Reliability of Flortaucipir F 18 PET Scan Interpretation
- ClinicalTrials.gov ID
- NCT03901092
- Acronym / sponsor ID
- 18F-AV-1451-FR01
- Conditions
- Alzheimer Disease
- Keywords
- flortaucipir F 18, Positron Emission Tomography, 18F-AV-1451, Diagnostic imaging, Tau imaging
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 242 participants (actual)
- Lead sponsor
- Avid RadiopharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 26 Mar 2019 (actual)
- Primary completion
- 26 Apr 2019 (actual)
- Study completion
- 26 Apr 2019 (actual)
- First posted
- 3 Apr 2019 (actual)
- Results
- Posted 11 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the performance of physician readers trained to read flortaucipir-PET (positron emission tomography) scans.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Physician PET scan readers are participants, blinded to demographic and clinical data from the source PET scans.
| Arm | Type | Receives |
|---|---|---|
| Flortaucipir PET Scan | Experimental | Drug: flortaucipir F 18Scans previously acquired from Study A16 (NCT02516046) and A05 (NCT02016560) will be read by independent, blinded readers. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| flortaucipir F 18Also: 18F-AV-1451, [F-18]T807, LY3191748No study drug will be administered. | Drug | Flortaucipir PET Scan |
Primary outcome
Primary Objective 1 Analysis 1: Diagnostic Performance of Individual Readers (NFT Score)
Time frame: baseline scan
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.
Primary Objective 1 Analysis 2: Diagnostic Performance of Individual Readers (NIA-AA Autopsy Diagnosis)
Time frame: baseline scan
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.
Primary Objective 2: Inter-reader Reliability of Reader Interpretation of Flortaucipir-PET Imaging
Time frame: baseline scan
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%.
5 secondary outcomes
Secondary Objective 1 Analysis 1: Diagnostic Performance of τAD++ Flortaucipir PET Images to Detect B3 NFTs
Time frame: baseline scan
Secondary Objective 1 Analysis 2: Diagnostic Performance of τAD++ Flortaucipir PET Images to Detect High ADNC
Time frame: baseline scan
Secondary Objective 2: Inter-reader Reliability of Reader Interpretation of τAD++ Flortaucipir PET Images
Time frame: baseline scan
Secondary Objective 3: Inter-reader Reliability of Flortaucipir PET Scan Interpretation in the Population of Intended Use
Time frame: baseline scan
Secondary Objective 4: Intra-reader Reliability of Reader Interpretation of Flortaucipir-PET Imaging
Time frame: baseline scan
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42467182Imabayashi E, Morris A, Iaccarino L, Arora AK, Kamiki E, Lu M. 18F-flortaucipir PET imaging: Biodistribution in the Japanese population and diagnostic accuracy by Japanese readers. Ann Nucl Med. 2026 Jul 17. doi: 10.1007/s12149-026-02239-4. Online ahead of print.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Avid Radiopharmaceuticals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing flortaucipir F 18 in people with Alzheimer Disease, run by Avid Radiopharmaceuticals at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Objective 1 Analysis 1: Diagnostic Performance of Individual Readers (NFT Score) (time frame: baseline scan). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03901092, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2020.