efficacy and safety of the pet imaging agent [18f]nav4694 in subjects with probable alzheimer's disease

Conditions: Alzheimer Disease

Summary: this is a phase 2, open-label, multiple-center, non-randomized single dose study to assess the safety and efficacy of \[18f\]nav4694 pet imaging in detecting beta-amyloid plaque in the brain in subjects with probable ad compared with healthy volunteers.


Eligibility criteria:
inclusion criteria: all participants: * is able to provide informed consent or assent, and exhibits adequate visual, auditory, and communication capabilities to enable compliance with study procedures * should be able to perform the psychometric testing * has a modified hachinski score ((hachinski, et al., 2012; rosen, et al., 1980) ≤ 4 at screening * possesses a general health that permits adequate compliance with all study procedures as ascertained by a detailed review of the medical history, surgical history, laboratory and physical examination findings, which must be performed within 56 days prior to administration of \[18f\]nav4694 * informed consent has been signed and dated by the subject and/or the subject's legally authorized representative (lar; for probable ad subjects) healthy volunteers only * is male or female and is between the age of 18 and 40 years (for younger hvs) or 55 to 85 years of age (for older hvs) * if female does not have childbearing potential: must be confirmed by either: post-menopausal status; or history of surgical sterilization or of hysterectomy * if female has childbearing potential: must demonstrate a negative serum beta-hcg level at screening and a negative urine pregnancy test on the day of injection (prior to injection) consistent with a non-gravid state and agree to use two acceptable forms of birth control * has no evidence of cognitive impairment as indicated by a clinical dementia rating (cdr) (morris, 1993) score of 0 (zero) and a score of ≥ 28 in the mini-mental state examination (mmse) (folstein, et al., 1975) * has mri brain scan that has been judged as "normal (age-appropriate)" supporting the lack of cerebrovascular disease (e.g., a white matter lesion score of 0, 1, or 2 and a basal ganglia score of 0 to 1 on the arwmc scale) probable alzheimer's disease subjects only * is male or female and is ≥ 55 of age, whereby females must be without childbearing potential (confirmed by either:post-menopausal status; or history of surgical sterilization or of hysterectomy) * presents with positive assessment for dementia of alzheimer's type in accordance with the dsm-iv-tr and probable ad according to the nincds-adrda criteria and fulfills none of the exclusion criteria of either * does not fulfill the international consensus criteria (icc) for probable diffuse lewy body disease (dlbd), the ninds-airen for probable vascular dementia, or the neary criteria for frontotemporal dementia (ftd) \[neary et al. 1998\] * has a mmse score between 16 and 23 * has a cdr (morris, 1993) score of 1 to 2 * has a cornell scale for depression in dementia (csdd; (alexopoulos, et al., 1988)) score less than or equal to 18 (definite major depression) * mri brain scan findings that do not reveal changes indicative of stroke and/or generalized cerebrovascular disease changes (limited to: a white matter lesion score of 0, 1, or 2 and a basal ganglia score of 0 or 1 on the arwmc scale) * has a caregiver who is willing and able to attend study visits and perform the psychometric tests requiring the presence of a caregiver exclusion criteria: * has any contraindication to mri examination, e.g., metal implants or phobia * is not able to lie down flat in the mri and pet scanners * is scheduled for surgery and/or another invasive procedure within the time period of up to 10 days after \[18f\]nav4694 application * is medically unstable and whose clinical course during the observation period is unpredictable, e.g., subjects within 14 days of myocardial infarction or stroke, unstable subjects with previous surgery (within 7 days), subjects with advanced heart insufficiency (nyha stage iv), or with acute renal failure * has a history of exposure to any radiation \> 30 msv in the last year (e.g., occupational, diagnostic imaging, or radiation therapy) * is receiving drug therapy or other treatment that is known to lead to greatly fluctuating values of the hematological or chemical laboratory parameters or to severe side effects (e.g., chemotherapy) * has received anti-amyloid immunotherapy * has been previously enrolled in this study and received \[18f\]nav4694 or participated in a clinical study involving an investigational pharmaceutical product within 30 days prior to screening, and/or any radiopharmaceutical within 10 radioactive half-lives prior to \[18f\]nav4694 administration * has a brain tumor or other intracranial lesion, a disturbance of cerebrospinal fluid (csf) circulation (e.g., normal pressure hydrocephalus) and/or a history of serious head trauma or brain surgery * has a history, physical, laboratory, or imaging findings indicative of a significant neurological or psychiatric illness (other than ad for the subjects with probable ad) * has another untreated disease that can cause disturbance of brain function (e.g. vitamin b12 or folic acid deficiency, disturbed thyroid function, anemia) * has a history of alcohol abuse or drug dependency in the 3 years prior to study entry or is an alcoholic or drug addict as determined by the investigator

Keywords: alzheimer