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

NCT03901105 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 18F-AV-1451-PX01
• Study Type: interventional
• Target: 205
• Locations: 1 country
• Sites: 1

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).

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Risk Ratio for AD Symptom Progression on Various Clinical Measures

  Within 18 months of scan

• Mean Change in Cognitive/Functional Assessments

  baseline and 18 months

• Inter-Reader Reliability of Reader Interpretation of Flortaucipir F 18 PET Imaging

  baseline scan

Study Arms (1)

Flortaucipir PET Scan

EXPERIMENTAL

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.

Drug: flortaucipir F18; Procedure: Brain PET Scan

Interventions

flortaucipir F18 DRUG

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

Also known as: 18F-AV-1451, [F-18]T807, LY3191748

Flortaucipir PET Scan

Brain PET Scan PROCEDURE

positron emission tomography (PET) scan of the brain

Flortaucipir PET Scan

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Avid Radiopharmaceuticals: lead

Study Sites (1)

American College of Radiology

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• 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.

  PMID: 33587110 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Medical Director
• Organization: Avid Radiopharmaceuticals, Inc.

clinicaloperations@avidrp.com

215-298-0700

Study Officials

• Study Director

  Avid Radiopharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Masking Details: PET scans were obtained in an open-label fashion.
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Physician PET scan readers are participants, blinded to demographic and clinical data from the source PET scans.

Study Record Dates

• First Submitted: March 28, 2019
• First Posted: April 3, 2019
• Study Start: March 28, 2019
• Primary Completion: April 28, 2019
• Study Completion: April 28, 2019
• Last Updated: August 28, 2020
• Results First Posted: August 28, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)