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

Phase 3

Completed

• Conditions: Alzheimer Disease
• Interventions: Drug: flortaucipir F18; Procedure: Brain PET Scan

• Registration Number: NCT03901105
• Lead Sponsor: Avid Radiopharmaceuticals

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2019-03-28
• Study First Submitted: 2019-03-28
• Study First Submitted QC: 2019-04-01
• Study First Posted: 2019-04-03
• Primary Completion: 2019-04-28
• Study Completion: 2019-04-28
• Disposition First Submitted: 2020-01-22
• Results First Submitted: 2020-06-27
• Status Verified: 2020-08
• Results First Submitted QC: 2020-08-21
• Disposition First Submitted QC: 2020-08-21
• Last Update Submitted: 2020-08-21
• Results First Posted: 2020-08-28
• Disposition First Posted: 2020-08-28
• Last Update Posted: 2020-08-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 205

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Flortaucipir PET Scan	flortaucipir F18	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.
Flortaucipir PET Scan	Brain 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.

Primary Outcome Measures

Name	Time	Method
Risk Ratio for AD Symptom Progression on CDR-SB	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 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

Name	Time	Method
Mean Change in Cognitive/Functional Assessments	baseline and 18 months	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	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 -1 to 1 with 1 indicating perfect agreement between the readers. Read results binarized as τAD++ or non-τAD++.
Risk Ratio for AD Symptom Progression on Various Clinical Measures	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.

Trial Locations

Locations (1)

American College of Radiology; 🇺🇸 Philadelphia, Pennsylvania, United States