Alzheimer Disease, Mild Cognitive Impairment
Conditions
Brief summary
A Phase 1 study designed to evaluate imaging characteristics of flortaucipir in the preclinical, prodromal and dementia phases of Alzheimer's disease.
Detailed description
The Australian Imaging Biomarkers and Lifestyle Study (AIBL) is a multicenter multidisciplinary study of Alzheimer's disease and aging funded by the Commonwealth Scientific and Industrial Research Organisation (CSIRO) Flagship Initiative, involving research centers in both Victoria and Western Australia. The goal of the A08 protocol was to further investigate the positron emission tomography (PET) imaging results with flortaucipir in patients across the AD spectrum from individuals with subjective memory complaints (SMC) to those with dementia, based on recruitment into the parent AIBL study.
Interventions
DRUGFlortaucipir F18
IV injection, 240 megabecquerel (MBq) (6.5 mCi)
PROCEDUREBrain PET scan
positron emission tomography (PET) scan of the brain
Sponsors
Avid Radiopharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Meet all inclusion criteria for the AIBL study protocol, with amyloid PET conducted or planned and MRI available * Subjects in the MCI and AD groups required to have a reliable caregiver capable of providing information about the subjects' symptoms
Exclusion criteria
* lifetime history of schizophrenia, schizoaffective disorder, or bipolar disorder * history of electroconvulsive therapy * MRI contraindicated * claustrophobic or, otherwise, unable to tolerate the imaging procedure * current clinically significant cardiovascular disease or clinically significant abnormalities on screening electrocardiogram * history of additional risk factors for Torsades de Pointes * current clinically significant infectious disease, endocrine or metabolic disease, or pulmonary, renal, or hepatic impairment that the investigator believes would affect study participation * history of cancer (other than skin or in situ prostate cancer) within the previous 5 years * current drug or alcohol abuse/dependence * history of alcohol abuse/dependence with 2 years of the onset of the symptoms of dementia * females of childbearing potential who were not surgically sterile, not refraining from sexual activity, or not using reliable methods of contraception
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Flortaucipir PET Imaging (Quantitative) | baseline scan | Flortaucipir PET cortical weighted average standardized uptake value ratio (SUVr). For SUVr, a value of 1 signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain. |
| Number of Participants With Advanced AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | baseline scan | Scans were visually read independently by two expert readers at the sponsor, blinded to any clinical information. Subject scans were categorized as follows: Advanced AD Scan Pattern (τAD++), Moderate AD Scan Pattern (τAD+), Not AD Scan Pattern (τAD-). For this analysis, subjects with Advanced (τAD++) scans were analyzed vs. the combined Moderate and Not AD pattern groups (τAD+/τAD-). Amyloid status was obtained by florbetapir or carbon-11-labeled Pittsburgh compound B (\[C-11\] PiB) PET results available from the parent AIBL study. |
| Number of Participants With AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | baseline scan | Scans were visually read independently by two expert readers at the sponsor, blinded to any clinical information. Subject scans were categorized as follows: Advanced AD Scan Pattern (τAD++), Moderate AD Scan Pattern (τAD+), Not AD Scan Pattern (τAD-). For this analysis, subjects with AD Pattern scans (Advanced \[τAD++\] and Moderate \[τAD+\] Scan Pattern) were combined vs. the Not AD pattern group (τAD-). Amyloid status was obtained by florbetapir or carbon-11-labeled Pittsburgh compound B (\[C-11\] PiB) PET results available from the parent AIBL study. |
Participant flow
Recruitment details
Enrollment occurred between Oct 2014 and Feb 2018 from the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL)
Participants by arm
| Arm | Count |
|---|---|
| Alzheimer's Disease (AD) Alzheimer's disease subjects receiving a flortaucipir PET scan at baseline and 12 months | 5 |
| Mild Cognitive Impairment (MCI) Mild cognitive impairment subjects receiving a flortaucipir PET scan at baseline and 12 months | 11 |
| Subjective Memory Complainers (SMC) Subjective memory complainers receiving a flortaucipir PET scan at baseline and 12 months | 45 |
| Cognitively Normal (CN) Cognitively normal subjects receiving a flortaucipir PET scan at baseline and 12 months | 25 |
| Total | 86 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 1 |
| Overall Study | Physician Decision | 1 | 0 | 2 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 3 | 3 |
Baseline characteristics
| Characteristic | Alzheimer's Disease (AD) | Mild Cognitive Impairment (MCI) | Subjective Memory Complainers (SMC) | Cognitively Normal (CN) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 76.2 years STANDARD_DEVIATION 6.53 | 74.3 years STANDARD_DEVIATION 5.82 | 77 years STANDARD_DEVIATION 7.43 | 72.9 years STANDARD_DEVIATION 4.67 | 75.4 years STANDARD_DEVIATION 6.64 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 11 Participants | 45 Participants | 25 Participants | 86 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Mini Mental Status Exam (MMSE) | 22.6 units on a scale STANDARD_DEVIATION 3.21 | 25.5 units on a scale STANDARD_DEVIATION 2.84 | 28 units on a scale STANDARD_DEVIATION 1.66 | 28.6 units on a scale STANDARD_DEVIATION 0.99 | 27.5 units on a scale STANDARD_DEVIATION 2.35 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 11 Participants | 44 Participants | 25 Participants | 85 Participants |
| Region of Enrollment Australia | 5 participants | 11 participants | 45 participants | 25 participants | 86 participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 26 Participants | 13 Participants | 45 Participants |
| Sex: Female, Male Male | 3 Participants | 7 Participants | 19 Participants | 12 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 11 | 0 / 45 | 0 / 25 |
| other Total, other adverse events | 0 / 5 | 0 / 11 | 1 / 45 | 1 / 25 |
| serious Total, serious adverse events | 0 / 5 | 0 / 11 | 0 / 45 | 0 / 25 |
Outcome results
Primary
Flortaucipir PET Imaging (Quantitative)
Flortaucipir PET cortical weighted average standardized uptake value ratio (SUVr). 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: baseline scan
Population: Inclusion in this analysis required that the subject's flortaucipir scan was analyzable for SUVr (1 AD, 1 MCI, 5 SMC, and 3 CN were not analyzable)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Alzheimer's Disease (AD) | Flortaucipir PET Imaging (Quantitative) | 1.31 standardized uptake value ratio (SUVr) | Standard Error 0.059 |
| Mild Cognitive Impairment (MCI) | Flortaucipir PET Imaging (Quantitative) | 1.13 standardized uptake value ratio (SUVr) | Standard Error 0.033 |
| Objectively Impaired | Flortaucipir PET Imaging (Quantitative) | 1.15 standardized uptake value ratio (SUVr) | Standard Error 0.031 |
| Subjective Memory Complainers (SMC) | Flortaucipir PET Imaging (Quantitative) | 1.08 standardized uptake value ratio (SUVr) | Standard Error 0.016 |
| Cognitively Normal (CN) | Flortaucipir PET Imaging (Quantitative) | 1.04 standardized uptake value ratio (SUVr) | Standard Error 0.028 |
| Non-objectively Compared | Flortaucipir PET Imaging (Quantitative) | 1.07 standardized uptake value ratio (SUVr) | Standard Error 0.015 |
p-value: 0.2161ANOVA
p-value: 0.0005ANOVA
p-value: <0.0001ANOVA
Primary
Number of Participants With AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status
Scans were visually read independently by two expert readers at the sponsor, blinded to any clinical information. Subject scans were categorized as follows: Advanced AD Scan Pattern (τAD++), Moderate AD Scan Pattern (τAD+), Not AD Scan Pattern (τAD-). For this analysis, subjects with AD Pattern scans (Advanced \[τAD++\] and Moderate \[τAD+\] Scan Pattern) were combined vs. the Not AD pattern group (τAD-). Amyloid status was obtained by florbetapir or carbon-11-labeled Pittsburgh compound B (\[C-11\] PiB) PET results available from the parent AIBL study.
Time frame: baseline scan
Population: Rows display flortaucipir scan results by subjects who were amyloid positive and amyloid negative at baseline.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Alzheimer's Disease (AD) | Number of Participants With AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Positive | AD Pattern Scan (Advanced or Moderate) | 2 Participants |
| Alzheimer's Disease (AD) | Number of Participants With AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Positive | Not AD Pattern Scan | 2 Participants |
| Alzheimer's Disease (AD) | Number of Participants With AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Negative | AD Pattern Scan (Advanced or Moderate) | 1 Participants |
| Alzheimer's Disease (AD) | Number of Participants With AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Negative | Not AD Pattern Scan | 0 Participants |
| Mild Cognitive Impairment (MCI) | Number of Participants With AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Positive | Not AD Pattern Scan | 1 Participants |
| Mild Cognitive Impairment (MCI) | Number of Participants With AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Negative | AD Pattern Scan (Advanced or Moderate) | 0 Participants |
| Mild Cognitive Impairment (MCI) | Number of Participants With AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Negative | Not AD Pattern Scan | 6 Participants |
| Mild Cognitive Impairment (MCI) | Number of Participants With AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Positive | AD Pattern Scan (Advanced or Moderate) | 4 Participants |
| Objectively Impaired | Number of Participants With AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Negative | AD Pattern Scan (Advanced or Moderate) | 6 Participants |
| Objectively Impaired | Number of Participants With AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Positive | Not AD Pattern Scan | 9 Participants |
| Objectively Impaired | Number of Participants With AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Negative | Not AD Pattern Scan | 19 Participants |
| Objectively Impaired | Number of Participants With AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Positive | AD Pattern Scan (Advanced or Moderate) | 11 Participants |
| Subjective Memory Complainers (SMC) | Number of Participants With AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Negative | Not AD Pattern Scan | 20 Participants |
| Subjective Memory Complainers (SMC) | Number of Participants With AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Positive | Not AD Pattern Scan | 4 Participants |
| Subjective Memory Complainers (SMC) | Number of Participants With AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Positive | AD Pattern Scan (Advanced or Moderate) | 0 Participants |
| Subjective Memory Complainers (SMC) | Number of Participants With AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Negative | AD Pattern Scan (Advanced or Moderate) | 1 Participants |
p-value: 0.0646Cochran-Mantel-Haenszel
Primary
Number of Participants With Advanced AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status
Scans were visually read independently by two expert readers at the sponsor, blinded to any clinical information. Subject scans were categorized as follows: Advanced AD Scan Pattern (τAD++), Moderate AD Scan Pattern (τAD+), Not AD Scan Pattern (τAD-). For this analysis, subjects with Advanced (τAD++) scans were analyzed vs. the combined Moderate and Not AD pattern groups (τAD+/τAD-). Amyloid status was obtained by florbetapir or carbon-11-labeled Pittsburgh compound B (\[C-11\] PiB) PET results available from the parent AIBL study.
Time frame: baseline scan
Population: Rows display flortaucipir scan results by subjects who were amyloid positive and amyloid negative at baseline
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Alzheimer's Disease (AD) | Number of Participants With Advanced AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Positive | Not Advanced AD Pattern | 2 Participants |
| Alzheimer's Disease (AD) | Number of Participants With Advanced AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Negative | Advanced AD Scan Pattern (τAD++) | 1 Participants |
| Alzheimer's Disease (AD) | Number of Participants With Advanced AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Positive | Advanced AD Scan Pattern (τAD++) | 2 Participants |
| Alzheimer's Disease (AD) | Number of Participants With Advanced AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Negative | Not Advanced AD Pattern | 0 Participants |
| Mild Cognitive Impairment (MCI) | Number of Participants With Advanced AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Negative | Advanced AD Scan Pattern (τAD++) | 0 Participants |
| Mild Cognitive Impairment (MCI) | Number of Participants With Advanced AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Negative | Not Advanced AD Pattern | 6 Participants |
| Mild Cognitive Impairment (MCI) | Number of Participants With Advanced AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Positive | Not Advanced AD Pattern | 2 Participants |
| Mild Cognitive Impairment (MCI) | Number of Participants With Advanced AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Positive | Advanced AD Scan Pattern (τAD++) | 3 Participants |
| Objectively Impaired | Number of Participants With Advanced AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Positive | Advanced AD Scan Pattern (τAD++) | 9 Participants |
| Objectively Impaired | Number of Participants With Advanced AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Negative | Not Advanced AD Pattern | 22 Participants |
| Objectively Impaired | Number of Participants With Advanced AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Positive | Not Advanced AD Pattern | 11 Participants |
| Objectively Impaired | Number of Participants With Advanced AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Negative | Advanced AD Scan Pattern (τAD++) | 3 Participants |
| Subjective Memory Complainers (SMC) | Number of Participants With Advanced AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Negative | Not Advanced AD Pattern | 20 Participants |
| Subjective Memory Complainers (SMC) | Number of Participants With Advanced AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Positive | Not Advanced AD Pattern | 4 Participants |
| Subjective Memory Complainers (SMC) | Number of Participants With Advanced AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Negative | Advanced AD Scan Pattern (τAD++) | 1 Participants |
| Subjective Memory Complainers (SMC) | Number of Participants With Advanced AD Pattern Flortaucipir PET Scan and Relationship to Cognitive Status | Amyloid Positive | Advanced AD Scan Pattern (τAD++) | 0 Participants |
p-value: 0.1998Cochran-Mantel-Haenszel