GE-067-005 will investigate the efficacy of the Flutemetamol (18F) Injection PET tracer for predicting the conversion from amnestic Mild Cognitive Impairment to probable Alzheimer’s disease. Uptake assessments will be based on the visual and quantitative evaluation of Flutemetamol (18F) Injection PET scans. Quantitative evaluations will be performed separately and the independent readers will be blinded to this result. MedDRA version: 14.1 Level: HLGT
Conditions
Interventions
Product Name: Flutemetamol (18F) Injection
Product Code: AH110690 (18F) Injection
Pharmaceutical Form: Solution for injection
INN or Proposed INN: [18F]
Sponsors
GE Healthcare Ltd and its Affiliates
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The enrollment of subjects from racial/ethic minority populations is strongly encouraged. Subjects may be included in the study if they meet all of the following criteria: (1) The subject has at least a six grade education or has a good work history (sufficient to exclude mental retardation). (2) The subject’s general health is adequate to comply with study procedures, as ascertained by review of their screening medical history and physical examination. (3) For women who are either surgically sterile (have had a documented bilateral oophorectomy and/or documented hysterectomy) or are postmenopausal (cessation of menses for more than 2 years), enrollment in the study without a pregnancy test at screening will be allowed. For women of childbearing potential, the results of a serum and urine human chorionic gonadotropin pregnancy test (with the result known on the day of and before IMP administration) must be negative. (4) The subject and/or the subject’s legally acceptable representative, if applicable, in accordance with local regulations, has signed and dated an informed consent. (5) The subject is 55 years old or older. (6) The subject meets Petersen criteria for amnestic MCI including: a. The subject must have a memory complaint or a study partner that can verify a memory complaint b. Abnormal memory function using the scoring on the Logical Memory II subscale revised (delayed paragraph recall) from the Wechsler Memory scale-Revised. i. Less than or equal to 11 for 16 or more years of education ii. Less than or equal to 9 for 8-15 years of education iii. Less than or equal to 6 for 0-7 years of education c. CDR global rating of 0.5 d. General cognition and functional ADL performance sufficiently preserved such that the diagnosis of possible or probable AD by NINCDS-ADRDA criteria cannot be made at screening e. An informant is available who has frequent contact with the subject and can accompany the subject to all clinic visits or be available to talk on the telephone about the subject’s memory. (7) The subject has a score of less than or equal to 4 on the Modified Hachinski Ischemic Scale. (8) The subject has a MMSE score of 24-30 (exceptions may be made for subjects with less than 8 years of education at the discretion of the Invesigator). (9) The subject has adequate visual and auditory acuity to allow neuropsychological testing. (10) The subject has a non-contrast MRI examination as part of the screening visit or within the previous 6 months that excludes MCI arising from structural causes (e.g. vascular disease, hydrocephalus) and is of sufficient diagnostic quality (details provided in Imaging Manual) for Volume of Interest (VOI) definition. (11) The subject is willing and able to participate for at least 3 years. (12) The subject has a Hamilton Depression Scale Score of less than or equal to
Exclusion criteria
Exclusion criteria: Subjects must be excluded from participating in this study if they meet any of the following criteria: (1) The subject has participated in any other clinical study utilizing an investigational agent within 30 days of study entry. (2) The subject is pregnant or lactating. (3) The subject has a history of alcohol and/or drug abuse within the last 2 years based upon a review of medical records. (4) 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. (5) 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. (6) The subject has major depression, bipolar disorder, as described in the DSM-IV within the past 1 year. (7) The subject has history of schizophrenia (DSM-IV criteria). (8) The subject has had, within the prior 3 months, psychotic features, agitation, or behavioural problems that could lead to protocol compliance issues. (9) The subject has a known or suspected hypersensitivity/allergy to [18F]flutemetamol or to any of the excipients. (10) The subject has significant abnormalities in serum B12, folate or thyroid functions that might interfere with the study. (11) The subject regularly took medication with known anticholinergic effects (which could impair memory) within the last 3 months or in the view of the Investigator the subject is taking a drug that could impair cognition. a. Patients on psychoactive medications e.g. certain antidepressants, neuro- leptics, chronic anxiolytics, or sedative hypnotics are excluded. Note: subjects may take stable doses of antidepressants lacking anticholinergic side effects, if they are not currently depressed and have not had a history of a major depressive episode within the past 2 years.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To compare the time to conversion to probable Alzheimer’s Disease (AD) in amnestic Mild Cognitive Impairment (aMCI) subjects with normal and abnormal patterns of [18F]flutemetamol uptake based on the visual assessment of a Positron Emission Tomography (PET) scan by independent, blinded readers.; Secondary Objective: •To compare the proportions of normal and abnormal subjects who convert to probable AD within the follow-up period. •To compare the time to conversion to probable AD in aMCI subjects with [18F]flutemetamol uptake below and above a pre-defined threshold based on quantitative assessment of a Flutemetamol (18F) Injection PET scan. •To determine the sensitivity and specificity of the ability of [18F]flutemetamol uptake to predict eventual conversion to probable AD based on clinical testing in the time period of the study conduct. Separate determinations will be made for blinded visual image assessments and the categorisation of quantitative image assessments. ;Primary end point(s): The primary endpoint is the time to conversion to probable AD of aMCI subjects with normal and abnormal patterns of [18F]flutemetamol uptake based on the independent, blinded visual assessment of a PET scan: Time 0 is the date of PET imaging.;Timepoint(s) of evaluation of this end point: Each subject will be assessed by the site every 6 months until they convert to AD, or, if they do not convert, until either 3 years has elapsed from imaging or the required number of conversions is reached (whichever occurs later). Once a subject converts, he/she will have reached the endpoint of the trial and no further follow-up wll be conducted for that subject. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Each subject will be assessed by the site every 6 months until they convert to AD, or, if they do not convert, until either 3 years has elapsed from imaging or the required number of conversions is reached (whichever occurs later). Once a subject converts, he/she will have reached the endpoint of the trial and no further follow-up wll be conducted for that subject.;Secondary end point(s): See objectives. | — |
Countries
United Kingdom, United States
Contacts
Public ContactRegGEHealthcare@ge.com
GE Healthcare
Outcome results
None listed