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

Primary Purpose

Alzheimer Disease

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Flortaucipir F18
Brain PET Scan
Whole body PET scan
Florbetapir F 18
Brain MRI
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

20 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • WCCT Global, LLC
  • Hoag Memorial Hospital Presbyterian

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Other

Arm Label

Brain flortaucipir PET scan

Whole body flortaucipir PET scan

MRI and Amyloid Extension Cohort

Arm Description

Subjects receiving a brain PET scan after flortaucipir administration

Subjects receiving a whole body PET scan after flortaucipir administration

Magnetic resonance imaging (MRI) scans and amyloid scans for subjects previously participating in Study T807000 (NCT01733355)

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
July 8, 2020
Last Updated
September 3, 2020
Sponsor
Avid Radiopharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT04474405
Brief Title
Exploratory Evaluation of Flortaucipir Injection in Healthy Volunteers and Cognitively Impaired Subjects
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
August 16, 2013 (Actual)
Primary Completion Date
December 9, 2013 (Actual)
Study Completion Date
December 9, 2013 (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
No

5. Study Description

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

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
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Brain flortaucipir PET scan
Arm Type
Experimental
Arm Description
Subjects receiving a brain PET scan after flortaucipir administration
Arm Title
Whole body flortaucipir PET scan
Arm Type
Experimental
Arm Description
Subjects receiving a whole body PET scan after flortaucipir administration
Arm Title
MRI and Amyloid Extension Cohort
Arm Type
Other
Arm Description
Magnetic resonance imaging (MRI) scans and amyloid scans for subjects previously participating in Study T807000 (NCT01733355)
Intervention Type
Drug
Intervention Name(s)
Flortaucipir F18
Other Intervention Name(s)
18F-AV-1451, [F-18]T807, LY3191748, Tauvid
Intervention Description
IV injection, 370 MBq (10 mCi), single dose
Intervention Type
Procedure
Intervention Name(s)
Brain PET Scan
Intervention Description
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).
Intervention Type
Procedure
Intervention Name(s)
Whole body PET scan
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Florbetapir F 18
Other Intervention Name(s)
Amyvid
Intervention Description
IV injection, 370 MBq (10 mCi), single dose
Intervention Type
Procedure
Intervention Name(s)
Brain MRI
Intervention Description
Volume-based T1-weighted Magnetic Resonance Imaging (MRI) of the brain
Primary Outcome Measure Information:
Title
Brain Flortaucipir Uptake
Description
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.
Time Frame
80-100 minutes postdose
Title
Flortaucipir Whole Body Effective Dose
Description
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.
Time Frame
injection to 6 hours postdose
Secondary Outcome Measure Information:
Title
Flortaucipir PET Correlations With Cognitive Assessments (Mini-mental State Exam)
Description
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.
Time Frame
at baseline
Title
Flortaucipir PET Correlations With Cognitive Assessments Cognitive Assessments (Digit Symbol Substitution Test)
Description
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.
Time Frame
at baseline
Title
Flortaucipir PET Correlations With Cognitive Assessments Cognitive Assessments (Alzheimer's Disease Assessment Scale)
Description
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.
Time Frame
at baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Avid Radiopharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
WCCT Global, LLC
City
Cypress
State/Province
California
ZIP/Postal Code
90630
Country
United States
Facility Name
Hoag Memorial Hospital Presbyterian
City
Newport Beach
State/Province
California
ZIP/Postal Code
92658
Country
United States

12. IPD Sharing Statement

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

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