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

Primary Purpose

Alzheimer Disease

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
flortaucipir F18
Brain PET Scan
Sponsored by
Avid Radiopharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Alzheimer Disease

Eligibility Criteria

55 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • American College of Radiology

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Flortaucipir PET Scan

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Mean Change in Cognitive/Functional Assessments
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.
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 τAD++ or non-τAD++.

Full Information

First Posted
March 28, 2019
Last Updated
August 21, 2020
Sponsor
Avid Radiopharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT03901105
Brief Title
Evaluation of Flortaucipir PET Signal and Cognitive Change in Early Alzheimer's Disease
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)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
March 28, 2019 (Actual)
Primary Completion Date
April 28, 2019 (Actual)
Study Completion Date
April 28, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Avid Radiopharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Model Description
Physician PET scan readers are participants, blinded to demographic and clinical data from the source PET scans.
Masking
None (Open Label)
Masking Description
PET scans were obtained in an open-label fashion.
Allocation
N/A
Enrollment
205 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Flortaucipir PET Scan
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
flortaucipir F18
Other Intervention Name(s)
18F-AV-1451, [F-18]T807, LY3191748
Intervention Description
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
Intervention Type
Procedure
Intervention Name(s)
Brain PET Scan
Intervention Description
positron emission tomography (PET) scan of the brain
Primary Outcome Measure Information:
Title
Risk Ratio for AD Symptom Progression on CDR-SB
Description
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.
Time Frame
Within 18 months of scan
Secondary Outcome Measure Information:
Title
Risk Ratio for AD Symptom Progression on Various Clinical Measures
Description
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.
Time Frame
Within 18 months of scan
Title
Mean Change in Cognitive/Functional Assessments
Description
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.
Time Frame
baseline and 18 months
Title
Inter-Reader Reliability of Reader Interpretation of Flortaucipir F 18 PET Imaging
Description
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++.
Time Frame
baseline scan

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Avid Radiopharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
American College of Radiology
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33587110
Citation
Lu M, Pontecorvo MJ, Devous MD Sr, Arora AK, Galante N, McGeehan A, Devadanam C, Salloway SP, Doraiswamy PM, Curtis C, Truocchio SP, Flitter M, Locascio T, Devine M, Zimmer JA, Fleisher AS, Mintun MA; AVID Collaborators. Aggregated Tau Measured by Visual Interpretation of Flortaucipir Positron Emission Tomography and the Associated Risk of Clinical Progression of Mild Cognitive Impairment and Alzheimer Disease: Results From 2 Phase III Clinical Trials. JAMA Neurol. 2021 Apr 1;78(4):445-453. doi: 10.1001/jamaneurol.2020.5505.
Results Reference
derived

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

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