Evaluation of Flortaucipir PET Signal and Cognitive Change in Early Alzheimer's Disease

Alzheimer Disease Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03901105
• Other study ID #: 18F-AV-1451-PX01
• Status: Completed
• Phase: Phase 3
• Start date: March 28, 2019
• Est. completion date: April 28, 2019

Study information

• Verified date: August 2020
• Source: Avid Radiopharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 205
• Est. completion date: April 28, 2019
• Est. primary completion date: April 28, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• flortaucipir F18
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

Procedure:
• Brain PET Scan
positron emission tomography (PET) scan of the brain

Locations

Country	Name	City	State
United States	American College of Radiology	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Avid Radiopharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Risk Ratio for AD Symptom Progression on CDR-SB	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.	Within 18 months of scan
Secondary	Risk Ratio for AD Symptom Progression on Various Clinical Measures	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.	Within 18 months of scan
Secondary	Mean Change in Cognitive/Functional Assessments	Mean change in cognitive/functional measures baseline between tAD++ and non-tAD++ (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.	baseline and 18 months
Secondary	Inter-Reader Reliability of Reader Interpretation of Flortaucipir F 18 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 -1 to 1 with 1 indicating perfect agreement between the readers. Read results binarized as tAD++ or non-tAD++.	baseline scan