Exploratory Evaluation of Flortaucipir Injection in Healthy Volunteers and Cognitively Impaired Subjects

An Exploratory Evaluation of the Tau Protein Binding Properties, Whole-Body Biodistribution and Safety of 18F-AV-1451 Injection in Healthy Volunteers and Cognitively Impaired Subjects

This early phase 1 study explored the brain uptake, retention, and safety of flortaucipir and obtained preliminary information regarding dosimetry of flortaucipir.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Flortaucipir F18; Procedure: Brain PET Scan; Drug: Florbetapir F 18; Procedure: Brain MRI; Procedure: Whole body PET scan

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630
      • WCCT Global, LLC
    • Newport Beach, California, United States, 92658
      • Hoag Memorial Hospital Presbyterian

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers had an Mini-Mental State Examination (MMSE) score of ≥ 29;
• MCI due to Alzheimer's disease (AD) consistent with National Institute on Aging (NIA)-Alzheimer's Association working group's on diagnostic guidelines for AD (Alzheimer's Dementia 7:270-9, 2011)
• Possible or probable AD: Met clinical criteria for possible or probable AD based on the NIA-Alzheimer's Association working group's on diagnostic guidelines for AD (Alzheimer's Dementia 7:263-9, 2011)

Exclusion Criteria:

• Current clinically significant psychiatric disease.
• Evidence of structural abnormalities such as major stroke or mass on MRI that would have made a diagnosis of impairment due to AD unlikely or was likely to interfere with interpretation of a PET scan on MRI.
• Claustrophobic or otherwise unable to tolerate the imaging procedure.
• Current clinically significant cardiovascular disease or clinically significant abnormalities on screening electrocardiogram (including, but not limited to, corrected QT interval >450 msec).
• Current clinically significant infectious disease, endocrine or metabolic disease, pulmonary, renal or hepatic impairment, or cancer
• History of alcohol abuse or substance abuse or dependence
• Female subjects of childbearing potential who were not surgically sterile, not refraining from sexual activity or not using reliable methods of contraception.
• Required medications with a narrow therapeutic window
• Received a non-study related radiopharmaceutical imaging or treatment procedure within 7 days prior to imaging session
• Receiving any investigational medications or had participated in a trial with investigational medications within the last 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brain flortaucipir PET scan; Subjects receiving a brain PET scan after flortaucipir administration	Drug: Flortaucipir F18; IV injection, 370 MBq (10 mCi), single dose; Other Names: 18F-AV-1451; [F-18]T807; LY3191748; Tauvid; Procedure: Brain PET Scan; positron emission tomography (PET) scan of the brain starting immediately after administration (60 minute dynamic imaging plus 4 frames x 5 minutes at approximately 80 minutes post-dose).; Drug: Florbetapir F 18; IV injection, 370 MBq (10 mCi), single dose; Other Names: Amyvid; Procedure: Brain MRI; Volume-based T1-weighted Magnetic Resonance Imaging (MRI) of the brain
Experimental: Whole body flortaucipir PET scan; Subjects receiving a whole body PET scan after flortaucipir administration	Drug: Flortaucipir F18; IV injection, 370 MBq (10 mCi), single dose; Other Names: 18F-AV-1451; [F-18]T807; LY3191748; Tauvid; Procedure: Whole body PET scan; positron emission tomography (PET) scan of the body from the vertex of the head to the thighs starting immediately following injection and repeated over 6 hours
Other: MRI and Amyloid Extension Cohort; Magnetic resonance imaging (MRI) scans and amyloid scans for subjects previously participating in Study T807000 (NCT01733355)	Procedure: Brain PET Scan; positron emission tomography (PET) scan of the brain starting immediately after administration (60 minute dynamic imaging plus 4 frames x 5 minutes at approximately 80 minutes post-dose).; Drug: Florbetapir F 18; IV injection, 370 MBq (10 mCi), single dose; Other Names: Amyvid; Procedure: Brain MRI; Volume-based T1-weighted Magnetic Resonance Imaging (MRI) of the brain

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain Flortaucipir Uptake	Brain imaging of tau in healthy volunteers and subjects with cognitive impairment. Standard uptake value ratios (SUVr), normalized to the entire cerebellum. A global cortical average volume of interest (VOI) is the average SUVr of the occipital cortex, parietal cortex, and temporal cortex. For SUVr, a value of 1 signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain.	80-100 minutes postdose
Flortaucipir Whole Body Effective Dose	Radiation dose estimates measured in millisieverts per megabecquerel (mSv/MBq) for the whole body obtained from Organ Level Internal Dose Assessment/Exponential Modeling (OLINDA/EXM) radiation dosimetry code. Results calculated using 73.7-kg man model.	injection to 6 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flortaucipir PET Correlations With Cognitive Assessments (Mini-mental State Exam)	Spearman's correlations between flortaucipir SUVr and cognitive function as measured on the Mini-Mental State Examination (MMSE). MMSE is a 30-point questionnaire that is used to measure cognitive impairment. 0 is the lowest score and 30 is the highest score, indicating normal cognitive function. Lower MMSE scores indicate worsening cognitive function. For this analysis, negative correlation values indicate that higher flortaucipir uptake is associated with decreasing cognitive function and positive correlation values indicate that lower flortaucipir uptake is associated with better cognitive function. 95% confidence interval uses a Fisher's z transformation.	at baseline
Flortaucipir PET Correlations With Cognitive Assessments Cognitive Assessments (Digit Symbol Substitution Test)	Spearman's correlations between flortaucipir SUVr and cognitive function as measured on Digit Symbol Substitution Test (DSST). The DSST is sensitive to the presence of cognitive dysfunction as well as to change in cognitive function. Scores range from 0 to 133. Lower DSST scores indicate worsening cognitive function. For this analysis, negative correlation values indicate that higher flortaucipir uptake is associated with decreasing cognitive function and positive correlation values indicate that lower flortaucipir uptake is associated with better cognitive function. 95% confidence interval uses a Fisher's z transformation.	at baseline
Flortaucipir PET Correlations With Cognitive Assessments Cognitive Assessments (Alzheimer's Disease Assessment Scale)	Spearman's correlations between flortaucipir SUVr and cognitive function as measured on a Modified Alzheimer's Disease Assessment Scale (ADAS)-Cognitive subscale (including orientation, verbal memory, language, and praxis, minus the spoken language assessment). Scores on the modified scale can range from 0 to 65. Higher scores indicate worsening cognitive function. For this analysis, positive correlation values indicate that higher flortaucipir uptake is associated with decreasing cognitive function and negative correlation values indicate that lower flortaucipir uptake is associated with better cognitive function. 95% confidence interval uses a Fisher's z transformation.	at baseline

Collaborators and Investigators

• Sponsor: Avid Radiopharmaceuticals
• Investigators: Study Director: Medical Director, Avid Radiopharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2013
• Primary Completion (Actual): December 9, 2013
• Study Completion (Actual): December 9, 2013

Study Registration Dates

• First Submitted: July 8, 2020
• First Submitted That Met QC Criteria: July 15, 2020
• First Posted (Actual): July 16, 2020

Study Record Updates

• Last Update Posted (Actual): September 25, 2020
• Last Update Submitted That Met QC Criteria: September 3, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 18F-AV-1451-A01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No