Evaluation of Flortaucipir PET Signal and Cognitive Change in Early Alzheimer's Disease
August 21, 2020 updated by: Avid Radiopharmaceuticals
Evaluation of the Relationship Between Baseline Flortaucipir PET Signal and Cognitive Change in Subjects With Early Alzheimer's Disease Participating in the I8D-MC-AZES Protocol Addendum D5010C00009 (2.1) (Tau Imaging)
This study will evaluate whether visual interpretation of flortaucipir-PET (positron emission tomography) scans, examining patterns of tracer uptake at baseline, can predict the rate of clinically-meaningful cognitive decline due to AD after 18 months.
All scans are acquired from cohorts of a previously completed study, I8D-MC-AZES (NCT02245737, lanabecestat, Eli Lilly and Company sponsor).
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
205
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- American College of Radiology
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
55 years to 85 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Scan Reader Criteria (5 total readers):
- Board-certified in radiology or nuclear medicine
- Professional experience interpreting PET scans
Scan Criteria (205 total scans):
- Former enrollment in AZES Study
- Flortaucipir scan at baseline
- clinical dementia rating - sum of boxes (CDR-SB) assessment at 18 months
Scan Study Population (AZES Study):
- 55 to 85 years
- MCI due to AD or probable AD by National Institute on Aging-Alzheimer's Association criteria (Albert 2011
- mini-mental status exam (MMSE) of 20 to 30 inclusive
- CDR global score of 0.5 (MCI), or 0.5 or 1 (AD) with a memory box score ≥ 0.5, and a score of ≤85 on the Delayed Memory Index of the Repeatable Battery for the Assessment of Neuropsychological Status.
- Amyloid positive status confirmed by florbetapir PET or lumbar puncture
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Experimental: Flortaucipir PET Scan
No study drug will be administered.
Scans previously acquired from Study I8D-MC-AZES (NCT02245737, Eli Lilly and Company sponsor) will be read by independent, blinded readers.
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No study drug will be administered.
Scans previously acquired from Study I8D-MC-AZES (NCT02245737, Eli Lilly and Company sponsor) at baseline will be read by independent, blinded readers.
IV injection, 240 megabecquerel (MBq) (6.5 mCi), single dose in AZES
Other Names:
positron emission tomography (PET) scan of the brain
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Risk Ratio for AD Symptom Progression on CDR-SB
Time Frame: Within 18 months of scan
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Baseline flortaucipir F 18 PET imaging results were determined by majority read (see Baseline Characteristics for description).
Clinically meaningful deterioration (CMD) was defined for the primary endpoint as a worsening of the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score of one point or more.
The clinical dementia rating (CDR) examines 6 categories of cognitive functioning domains.
Each domain is scored on a scale ranging from 0 to 3 (including 0.5).
A CDR-SB was generated as the sum of the values in each of the 6 domains.
The CDR-SB sum scores range from 0 to 18, with higher scores indicating greater cognitive impairment and a 1 point worsening is considered a clinically significant symptom change.
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Within 18 months of scan
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Risk Ratio for AD Symptom Progression on Various Clinical Measures
Time Frame: Within 18 months of scan
|
Baseline flortaucipir F 18 PET imaging results were determined by majority read (see Baseline Characteristics for description).
Clinically meaningful deterioration (CMD) was defined for the cognitive endpoints as follows: mini-mental status exam (MMSE) worsening of 3 points or greater, Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) worsening of 4 points or greater, Pfeffer's Functional Activities Questionnaire (FAQ) worsening of 3 points or greater, CDR global worsening of greater than 0 points.
MMSE scores range from 0 to 30 with lower scores indicating worsening cognitive function.
ADAS-Cog11 scores range from 0 to 70 with higher scores indicating worsening cognitive function.
FAQ scores range from 0 to 30 with higher scores indicating worsening cognitive function.
CDR global is scored on a 5 point scale (0, 0.5, 1, 2, 3) with higher scores indicating worsening cognitive function.
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Within 18 months of scan
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Mean Change in Cognitive/Functional Assessments
Time Frame: baseline and 18 months
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Mean change in cognitive/functional measures baseline between τAD++ and non-τAD++ (determined by baseline tau status), calculated by Mixed Model Repeat Measures (MMRM).
CDR-SB scores range from 0 to 18, with higher scores indicating worsening cognitive impairment.
MMSE scores range from 0 to 30 with lower scores indicating worsening cognitive function.
ADAS-Cog11 scores range from 0 to 70 with higher scores indicating worsening cognitive function.
FAQ scores range from 0 to 30 with higher scores indicating worsening cognitive function.
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baseline and 18 months
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Inter-Reader Reliability of Reader Interpretation of Flortaucipir F 18 PET Imaging
Time Frame: baseline scan
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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 -1 to 1 with 1 indicating perfect agreement between the readers.
Read results binarized as τAD++ or non-τAD++.
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baseline scan
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Study Director, Avid Radiopharmaceuticals
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 28, 2019
Primary Completion (Actual)
April 28, 2019
Study Completion (Actual)
April 28, 2019
Study Registration Dates
First Submitted
March 28, 2019
First Submitted That Met QC Criteria
April 1, 2019
First Posted (Actual)
April 3, 2019
Study Record Updates
Last Update Posted (Actual)
August 28, 2020
Last Update Submitted That Met QC Criteria
August 21, 2020
Last Verified
August 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 18F-AV-1451-PX01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
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