Frontotemporal Dementia
Conditions
Brief summary
This study is designed to assess the usefulness of flortaucipir in Positron Emission Tomography (PET) imaging for subjects diagnosed with Frontotemporal Dementia (FTD).
Interventions
DRUGFlortaucipir F18
370 megabecquerel (MBq)(10 millicurie \[mCi\]) injection, single dose
PROCEDUREBrain PET scan
positron emission tomography (PET) scan of the brain
Sponsors
Avid Radiopharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects diagnosed by a dementia specialist with symptomatic clinical syndromes with expected Frontotemporal Dementia (FTD) pathology will be enrolled. Clinical syndromes associated with FTD pathology include: behavioral-variant FTD, FTD with motor-neuron disease, non-fluent/agrammatic and semantic variants of primary progressive aphasia, progressive supranuclear palsy syndrome and corticobasal syndrome. * Have provided informed consent or have a legally authorized (LAR) provide consent for study procedures * Have had volumetric brain MRI obtained in site's companion protocol within one year of enrollment * Can tolerate PET scan procedures
Exclusion criteria
* Have clinically significant cardiac, hepatic, renal, pulmonary, metabolic, or endocrine disturbances that pose potential safety risk * Have history of risk factors for Torsades de Pointes (TdP) or taking medication known to cause QT prolongation * Have history of drug or alcohol dependence within the last year * Are females of childbearing potential who are not surgically sterile, not refraining from sexual activity, or not using reliable contraception * Have history of relevant severe drug allergy or hypersensitivity * Have received an investigational medication under FDA IND protocol within 30 days of planned imaging session * Have received a radiopharmaceutical for imaging/therapy within 24 hours of imaging session * Possess PET scan evidence of amyloid deposition * Determined by the investigator to be unsuitable for this type of study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Qualitative Evaluation of Flortaucipir PET Scans | baseline scan | Subject scans were visually evaluated by an expert reader into three groups. Advanced Alzheimer's Disease (AD) scan pattern = In either hemisphere, increased neocortical activity in the parietal/precuneus region(s), or frontal region(s) with increased uptake in the posterolateral temporal (PLT), parietal, or occipital region(s). Moderate AD scan pattern = In either hemisphere, increased neocortical activity limited to the PLT or occipital region(s). Not AD scan pattern = No increased neocortical activity, or increased neocortical activity isolated to the mesial temporal, anterolateral temporal, and/or frontal regions. |
| Quantitative Evaluation of Flortaucipir PET Scans | baseline scan | Standard Uptake Value Ratio (SUVr) using a weighted cortical average (MUBADA), and individual regions. For SUVr, a value of 1 or lower signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain. |
Countries
United States
Participant flow
Recruitment details
Enrollment occurred between Apr 2017 and Oct 2018.
Pre-assignment details
As a result of a positive amyloid scan at screening, 1 subject was discontinued prior to administration of flortaucipir. Two additional subjects had positive amyloid scans and received flortaucipir, but were excluded from the per protocol population results (n=13).
Participants by arm
| Arm | Count |
|---|---|
| FTD Subjects Subjects diagnosed by dementia specialist with a clinical Frontotemporal Dementia (FTD) syndrome and expected tau or TDP-43 pathology receiving a flortaucipir PET scan | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Positive amyloid scan | 3 |
Baseline characteristics
| Characteristic | FTD Subjects |
|---|---|
| Age, Continuous | 64.7 years STANDARD_DEVIATION 6.22 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| MMSE | 25.6 units on a scale STANDARD_DEVIATION 6.38 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 4 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Qualitative Evaluation of Flortaucipir PET Scans
Subject scans were visually evaluated by an expert reader into three groups. Advanced Alzheimer's Disease (AD) scan pattern = In either hemisphere, increased neocortical activity in the parietal/precuneus region(s), or frontal region(s) with increased uptake in the posterolateral temporal (PLT), parietal, or occipital region(s). Moderate AD scan pattern = In either hemisphere, increased neocortical activity limited to the PLT or occipital region(s). Not AD scan pattern = No increased neocortical activity, or increased neocortical activity isolated to the mesial temporal, anterolateral temporal, and/or frontal regions.
Time frame: baseline scan
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FTD Subjects | Qualitative Evaluation of Flortaucipir PET Scans | Advanced AD Scan Pattern (τAD++) | 0 Participants |
| FTD Subjects | Qualitative Evaluation of Flortaucipir PET Scans | Moderate AD Scan Pattern (τAD+) | 0 Participants |
| FTD Subjects | Qualitative Evaluation of Flortaucipir PET Scans | Not AD Scan Pattern (τAD-) | 13 Participants |
Primary
Quantitative Evaluation of Flortaucipir PET Scans
Standard Uptake Value Ratio (SUVr) using a weighted cortical average (MUBADA), and individual regions. For SUVr, a value of 1 or lower signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain.
Time frame: baseline scan
Population: All amyloid negative FTD subjects who had a PET scan that was able to be quantitatively evaluated (n=12). One subject did not have magnetic resonance imaging available, so quantitation was not possible.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FTD Subjects | Quantitative Evaluation of Flortaucipir PET Scans | Parietal | 0.91992 standardized uptake value ratio (SUVr) | Standard Deviation 0.054753 |
| FTD Subjects | Quantitative Evaluation of Flortaucipir PET Scans | MUBADA | 1.00903 standardized uptake value ratio (SUVr) | Standard Deviation 0.036582 |
| FTD Subjects | Quantitative Evaluation of Flortaucipir PET Scans | Temporal | 0.94920 standardized uptake value ratio (SUVr) | Standard Deviation 0.041189 |
| FTD Subjects | Quantitative Evaluation of Flortaucipir PET Scans | Frontal | 0.89825 standardized uptake value ratio (SUVr) | Standard Deviation 0.086118 |
| FTD Subjects | Quantitative Evaluation of Flortaucipir PET Scans | Caudate | 0.63508 standardized uptake value ratio (SUVr) | Standard Deviation 0.130466 |