Alzheimer's Disease, Mild Cognitive Impairment
Conditions
Keywords
Mild Cognitive Impairment, Positron Emission Tomography, National Institute of Neurological and Communicative Disorders and Stroke, Alzheimer's Disease and Related Disorders Association, Assess Prognostic Usefulness of Flutemetamol Injection for Identifying Subjects who will Convert to Clinically Probable Alzheimer's Disease
Brief summary
This study will investigate the efficacy of the Flutemetamol (18F) Injection PET tracer in identifying abnormal (18F) flutemetamol uptake patterns which predict the conversion from aMCI to a b-amyloid associated clinically probable Alzheimer's disease.
Interventions
DRUGFlutemetamol (18F) Injection
All subjects will receive an i.v. dose of (18F) flutemetamol (less than 10 mg flutemetamol). The nominal activity of a single administration of (18F) flutemetamol will be 185 MBq.
Sponsors
Medpace, Inc.
i3 Statprobe
i3 Research
Quintiles, Inc.
GE Healthcare
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The subject is 60 years old or older. * The subject meets the Petersen criteria for amnestic MCI. * The subject has a score of less than or equal to 4 on the Modified Hachinski Ischemic Scale. * The subject has a MMSE score of 24-30. * The subject has a non-contrast MRI examination as part of the screening visit that excludes aMCI arising from structural causes. * The subject and/or the subject's legally acceptable representative, if applicable, in accordance with local regulations, has signed and dated an informed consent.
Exclusion criteria
* The subject has any significant neurologic disease other than suspected aMCI; such as Parkinson's disease, Huntington's disease, normal pressure hydrocephalus, brain tumor, supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits, or known structural brain abnormalities. * The subject has one or more aneurysm clips, artificial heart valves, metal implants, embedded metal fragments or pacemakers that would pose a risk during an MRI. * The subject has major depression, bipolar disorder, as described in the DSM-IV within the past year. * The subject has history of schizophrenia (DSM-IV criteria). * The subject has had, within the prior 3 months, psychotic features, agitation or behavioral problems that could lead to protocol compliance issues.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hazard Ratio (HR) by PET Scan Readers for Conversion to Probable Alzheimer's Disease Based on Visual Image Interpretation. | Up to 36 months post flutemetamol administration | Visual Interpretation of the PET scan by independent readers. Note: The statistic Hazard ratio (HR) is the ratio of the hazard rates in the 2 groups (1 group being normal (negative for amyloid B) and 1 group being abnormal (positive for amyloid B). Under the null hypothesis of equal rates, the HR would be equal to 1. As the HR increases above 1, the chances of being probable Alzheimer's Disease (pAD) also increases. Note: Eight Subjects who withdrew prior to the first Clinical Adjudication Committee (CAC) evaluation are not included in the analysis. (232 - 8 = 224 Subjects included). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Up to 36 months post flutemetamol administration. | Numbers of subjects with normal and abnormal patterns of \[18F\]flutemetamol uptake who converted to pAD. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Flutemetamol (18F) Injection Flutemetamol (18F) Injection: All subjects will receive an i.v. dose of (18F) flutemetamol (less than 10 mg flutemetamol). The nominal activity of a single administration of (18F) flutemetamol will be 185 MBq. | 232 |
| Total | 232 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Patient Request | 11 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Screen Failure | 113 |
| Overall Study | Technical Problem | 1 |
| Overall Study | Terminated by Sponsor | 1 |
| Overall Study | Various reasons | 4 |
Baseline characteristics
| Characteristic | Flutemetamol (18F) Injection |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 169 Participants |
| Age, Categorical Between 18 and 65 years | 63 Participants |
| Age, Continuous | 71.1 years STANDARD_DEVIATION 8.62 |
| Region of Enrollment Belgium | 13 participants |
| Region of Enrollment Denmark | 8 participants |
| Region of Enrollment Finland | 15 participants |
| Region of Enrollment Sweden | 7 participants |
| Region of Enrollment United Kingdom | 80 participants |
| Region of Enrollment United States | 109 participants |
| Sex: Female, Male Female | 118 Participants |
| Sex: Female, Male Male | 114 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 232 |
| serious Total, serious adverse events | 1 / 232 |
Outcome results
Primary
Hazard Ratio (HR) by PET Scan Readers for Conversion to Probable Alzheimer's Disease Based on Visual Image Interpretation.
Visual Interpretation of the PET scan by independent readers. Note: The statistic Hazard ratio (HR) is the ratio of the hazard rates in the 2 groups (1 group being normal (negative for amyloid B) and 1 group being abnormal (positive for amyloid B). Under the null hypothesis of equal rates, the HR would be equal to 1. As the HR increases above 1, the chances of being probable Alzheimer's Disease (pAD) also increases. Note: Eight Subjects who withdrew prior to the first Clinical Adjudication Committee (CAC) evaluation are not included in the analysis. (232 - 8 = 224 Subjects included).
Time frame: Up to 36 months post flutemetamol administration
Population: Eight Subjects who withdrew prior to the first Clinical Adjudication Committee (CAC) evaluation are not included in the analysis. (232 - 8 = 224 Subjects included).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Hazard Ratio | Hazard Ratio (HR) by PET Scan Readers for Conversion to Probable Alzheimer's Disease Based on Visual Image Interpretation. | Reader 1 - Visual Interpretation | 3.418 Ratio of visual interpretations |
| Hazard Ratio | Hazard Ratio (HR) by PET Scan Readers for Conversion to Probable Alzheimer's Disease Based on Visual Image Interpretation. | Reader 2 - Visual Interpretation | 1.962 Ratio of visual interpretations |
| Hazard Ratio | Hazard Ratio (HR) by PET Scan Readers for Conversion to Probable Alzheimer's Disease Based on Visual Image Interpretation. | Reader 3 - Visual Interpretation | 2.561 Ratio of visual interpretations |
| Hazard Ratio | Hazard Ratio (HR) by PET Scan Readers for Conversion to Probable Alzheimer's Disease Based on Visual Image Interpretation. | Reader 4 - Visual Interpretation | 2.633 Ratio of visual interpretations |
| Hazard Ratio | Hazard Ratio (HR) by PET Scan Readers for Conversion to Probable Alzheimer's Disease Based on Visual Image Interpretation. | Reader 5 - Visual Interpretation | 2.580 Ratio of visual interpretations |
Secondary
The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period.
Numbers of subjects with normal and abnormal patterns of \[18F\]flutemetamol uptake who converted to pAD.
Time frame: Up to 36 months post flutemetamol administration.
Population: Eight Subjects who withdrew prior to the first Clinical Adjudication Committee (CAC) evaluation are not included in the analysis. (232 - 8 = 224 Subjects included).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Hazard Ratio | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Reader 3 - Abnormal | 35 Number of subjects |
| Hazard Ratio | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Reader 2 - Normal | 72 Number of subjects |
| Hazard Ratio | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Reader 4 - Normal | 98 Number of subjects |
| Hazard Ratio | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Majority Reads - Abnormal | 45 Number of subjects |
| Hazard Ratio | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Reader 4 - Abnormal | 45 Number of subjects |
| Hazard Ratio | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Reader 2 - Abnormal | 71 Number of subjects |
| Hazard Ratio | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Reader 5 - Normal | 98 Number of subjects |
| Hazard Ratio | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Reader 1 - Abnormal | 32 Number of subjects |
| Hazard Ratio | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Reader 5 - Abnormal | 45 Number of subjects |
| Hazard Ratio | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Reader 3 - Normal | 108 Number of subjects |
| Hazard Ratio | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Majority Reads - Normal | 98 Number of subjects |
| Hazard Ratio | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Reader 1 - Normal | 111 Number of subjects |
| Clinically Probable Alzheimer's Disease | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Majority Reads - Abnormal | 52 Number of subjects |
| Clinically Probable Alzheimer's Disease | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Reader 1 - Normal | 31 Number of subjects |
| Clinically Probable Alzheimer's Disease | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Reader 1 - Abnormal | 50 Number of subjects |
| Clinically Probable Alzheimer's Disease | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Reader 2 - Normal | 21 Number of subjects |
| Clinically Probable Alzheimer's Disease | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Reader 2 - Abnormal | 60 Number of subjects |
| Clinically Probable Alzheimer's Disease | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Reader 3 - Normal | 37 Number of subjects |
| Clinically Probable Alzheimer's Disease | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Reader 3 - Abnormal | 44 Number of subjects |
| Clinically Probable Alzheimer's Disease | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Reader 4 - Normal | 28 Number of subjects |
| Clinically Probable Alzheimer's Disease | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Reader 4 - Abnormal | 53 Number of subjects |
| Clinically Probable Alzheimer's Disease | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Reader 5 - Normal | 29 Number of subjects |
| Clinically Probable Alzheimer's Disease | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Reader 5 - Abnormal | 52 Number of subjects |
| Clinically Probable Alzheimer's Disease | The of Normal and Abnormal Subjects Who Convert to Probable Alzheimer's Disease (pAD) Within the Follow up Period. | Majority Reads - Normal | 29 Number of subjects |