Analysis of 18F-AV-1451 PET Imaging in Cognitively Healthy, MCI, and AD Subjects

NCT02016560 | Completed Phase 2 Results

• 1 other identifier: 18F-AV-1451-A05
• Study Type: interventional
• Target: 383
• Locations: 1 country
• Sites: 27

Brief Summary

A Phase 2/3 cross-sectional and longitudinal observational study evaluating imaging characteristics of flortaucipir in control subjects and patients with clinically defined MCI and AD dementia (AD).

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (3)

• Confirmatory Phase: Relationship Between Neocortical Flortaucipir Uptake and the Subsequent Rate of Cognitive Decline

  Confirm the relationship between neocortical flortaucipir uptake and the subsequent rate of cognitive decline at longitudinal follow up that was observed in the Exploratory Phase of the study. Patients were assigned to groups by majority classification of the flortaucipir positron emission tomography (PET) scan by five independent imaging physicians. Clinically meaningful cognitive and functional deterioration was defined as a 1 point or greater worsening on clinical dementia rating - sum of boxes (CDR-SB) score over the follow-up period.

  between baseline and 18 months

• Exploratory Phase: Cross-sectional Flortaucipir Imaging Results

  Flortaucipir standardized uptake value ratio (SUVr). A value of 1 signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain.

  baseline scan

• Exploratory Phase: Longitudinal Change in Tau Deposition Over Time, by Amyloid Status

  Assess the rate of change of tau deposition as measured by flortaucipir uptake (SUVr) over time. Change = 18 months SUVr - baseline SUVr.

  baseline and 18 months

Secondary Outcomes (2)

• Confirmatory Phase: Diagnostic Performance of Flortaucipir Visual Read

  baseline and 18 months

• Exploratory Phase: Correlation Between Flortaucipir SUVr and Age

  baseline scan

Study Arms (4)

Exploratory Cognitively Healthy Subjects

EXPERIMENTAL

Subjects will receive an IV injection, 370 megabecquerel (MBq) (10 millicurie \[mCi\]), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline.

Drug: florbetapir F 18; Drug: Flortaucipir F18; Procedure: Brain PET Scan

Exploratory MCI Subjects

EXPERIMENTAL

Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline, 9 months and 18 months.

Drug: florbetapir F 18; Drug: Flortaucipir F18; Procedure: Brain PET Scan

Exploratory AD Subjects

EXPERIMENTAL

Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline, 9 months and 18 months.

Drug: florbetapir F 18; Drug: Flortaucipir F18; Procedure: Brain PET Scan

Confirmatory Subjects

EXPERIMENTAL

Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 and flortaucipir at baseline.

Drug: florbetapir F 18; Drug: Flortaucipir F18; Procedure: Brain PET Scan

Interventions

florbetapir F 18 DRUG

Also known as: Amyvid, 18F-AV-45

Confirmatory Subjects; Exploratory AD Subjects; Exploratory Cognitively Healthy Subjects; Exploratory MCI Subjects

Flortaucipir F18 DRUG

Also known as: T807, 18F-AV-1451

Confirmatory Subjects; Exploratory AD Subjects; Exploratory Cognitively Healthy Subjects; Exploratory MCI Subjects

Brain PET Scan PROCEDURE

positron emission tomography (PET) scan of the brain

Confirmatory Subjects; Exploratory AD Subjects; Exploratory Cognitively Healthy Subjects; Exploratory MCI Subjects

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Exploratory Cognitively Healthy Subjects
• ≥ 20 to ≤ 40 years of age OR ≥ 50 years of age
• Mini-mental state examination (MMSE) ≥ 29
• No significant history of cognitive impairment
• Exploratory MCI Subjects
• ≥ 50 years of age
• MMSE ≥ 24
• Have MCI consistent with National Institute on Aging-Alzheimer's Association (NIA-AA) working group's diagnostic guidelines for AD
• Have a study partner that can report on subject's activities of daily living
• Exploratory AD Subjects
• ≥ 50 years of age
• MMSE \> 10
• Have possible or probable AD based on the NIA-AA working group's diagnostic guidelines for AD
• Have a study partner that can report on subject's activities of daily living
• Confirmatory Subjects

You may not qualify if:

• Current clinically significant psychiatric disease
• Evidence of structural brain abnormalities
• History of moderate or severe traumatic brain injury
• Current clinically significant cardiovascular disease or ECG abnormalities, or additional risk factors for Torsades de Pointes
• Current clinically significant infectious disease, endocrine or metabolic disease, pulmonary, renal or hepatic impairment, or cancer
• History of alcohol or substance abuse or dependence
• Females of childbearing potential who are not surgically sterile, not refraining from sexual activity or not using reliable methods of contraception
• Have received or participated in a trial with investigational medications in the past 30 days
• Have had a non-study related radiopharmaceutical imaging or treatment procedure within 7 days prior to the study imaging session.

Sponsors & Collaborators

• Avid Radiopharmaceuticals: lead

Study Sites (27)

Banner Alzheimer's Institute

Phoenix, Arizona, 85006, United States

Location

Four Peaks Neurology

Scottsdale, Arizona, 85258, United States

Location

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

Banner Sun Health Research Institute

Sun City, Arizona, 85351, United States

Location

UC Irvine

Irvine, California, 92697, United States

Location

Hoag Memorial

Newport Beach, California, 92663, United States

Location

Norther California PET Imaging Center

Sacramento, California, 95816, United States

Location

UC Davis

Sacramento, California, 95817, United States

Location

UC San Francisco

San Francisco, California, 94158, United States

Location

Neurological Research Institute

Santa Monica, California, 90404, United States

Location

Molecular NeuroImaging

New Haven, Connecticut, 06510, United States

Location

Quantum Laboratories

Deerfield Beach, Florida, 33064, United States

Location

21st Century Oncology

Fort Myers, Florida, 33912, United States

Location

Sandlake Imaging

Orlando, Florida, 32806, United States

Location

Meridien Research

St. Petersburg, Florida, 33709, United States

Location

USF Health Byrd Alzheimer's Center

Tampa, Florida, 33613, United States

Location

Independent Imaging

West Palm Beach, Florida, 33407, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston University

Boston, Massachusetts, 02118, United States

Location

Alzheimer's Disease Center

Quincy, Massachusetts, 02169, United States

Location

Center for Clinical Imaging Research

St Louis, Missouri, 63110, United States

Location

Las Vegas Radiology

Las Vegas, Nevada, 89147, United States

Location

Center for Brain Health - NYU Langone Medical Center

New York, New York, 10016, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Butler Hospital

Providence, Rhode Island, 02906, 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

florbetapir; 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

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Applies only to confirmatory phase: the independent readers are blinded to all clinical information.
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: All subjects in both the exploratory and confirmatory phases of the study, receive both florbetapir and florbetapir scans, regardless of subgroup assignment.

Study Record Dates

• First Submitted: December 16, 2013
• First Posted: December 20, 2013
• Study Start: December 1, 2013
• Primary Completion: July 28, 2017
• Study Completion: July 28, 2017
• Last Updated: September 22, 2020
• Results First Posted: August 24, 2020

Record last verified: 2020-09

Locations

US (27)