Efficacy and Safety of the PET Imaging Agent [18F]NAV4694 in Subjects With Probable Alzheimer's Disease
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: [18F]NAV4694 Single intravenous injection of 8.1 millicuries of [18F]NAV4694 |
Drug: [18F]NAV4694
|
Outcome Measures
Primary Outcome Measures
- [18F]NAV4694 PET visual assessment by centralized readers [25 minutes post injection]
To evaluate [18F]NAV4694 PET visual assessment by centralized readers for detection of cerebral beta-amyloid plaque in subjects diagnosed with probable Alzheimer's disease compared with similarly aged and young healthy volunteers.
Secondary Outcome Measures
- Assess the incidence of adverse events after a single dose of [18F]NAV4694 [7 Days]
To assess the incidence of adverse events after a single dose of [18F]NAV4694 PET in individuals diagnosed with probable AD and similarly aged and young healthy volunteers.
- Evaluate [18F]NAV4694 PET quantitative assessment [25 minutes post injection]
To evaluate [18F]NAV4694 PET quantitative assessment, by assessing standard uptake value ratios (SUVR) for detection of cerebral beta-amyloid plaque in subjects diagnosed with probable Alzheimer's disease compared with similarly aged and young healthy volunteers.
- Determine correlation of neuro-psychiatric tests with [18F]NAV4694 imaging [25 minutes post injection]
To determine the correlation of neuro-psychiatric tests with the beta-amyloid plaque burden determined by correlating various baseline neuro-psychiatric test scores with the [18F]NAV4694 PET imaging results in subjects diagnosed with probable AD
- Assess changes in laboratory values after a single dose of [18F]NAV4694 [7 days]
To assess changes in laboratory values after a single dose of [18F]NAV4694 PET in individuals diagnosed with probable AD and similarly aged and young healthy volunteers.
Eligibility Criteria
Criteria
Inclusion Criteria:
All participants:
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is able to provide informed consent or assent, and exhibits adequate visual, auditory, and communication capabilities to enable compliance with study procedures
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should be able to perform the psychometric testing
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has a modified Hachinski score ((Hachinski, et al., 2012; Rosen, et al., 1980) ≤ 4 at screening
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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
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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
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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)
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if female does not have childbearing potential: must be confirmed by either: post-menopausal status; or history of surgical sterilization or of hysterectomy
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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
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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)
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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
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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)
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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
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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]
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has a MMSE score between 16 and 23
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has a CDR (Morris, 1993) score of 1 to 2
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has a Cornell Scale for Depression in Dementia (CSDD; (Alexopoulos, et al., 1988)) score less than or equal to 18 (definite major depression)
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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)
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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:
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has any contraindication to MRI examination, e.g., metal implants or phobia
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is not able to lie down flat in the MRI and PET scanners
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is scheduled for surgery and/or another invasive procedure within the time period of up to 10 days after [18F]NAV4694 application
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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
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has a history of exposure to any radiation > 30 mSv in the last year (e.g., occupational, diagnostic imaging, or radiation therapy)
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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)
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has received anti-amyloid immunotherapy
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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
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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
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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)
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has another untreated disease that can cause disturbance of brain function (e.g. vitamin B12 or folic acid deficiency, disturbed thyroid function, anemia)
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Molecular NeuroImaging, LLC | New Haven | Connecticut | United States | 06510 |
| 2 | Rush University Medical Center | Chicago | Illinois | United States | 60612 |
| 3 | Alexian Brothers Neurosciences Institute | Elk Grove Village | Illinois | United States | 60007 |
| 4 | Indiana Medical Research | Indianapolis | Indiana | United States | 46202 |
| 5 | Brigham & Women's Hospital | Boston | Massachusetts | United States | 02115 |
| 6 | Alzheimer's Disease Center, Quincy Medical Center | Quincy | Massachusetts | United States | 02169 |
| 7 | Neurological Associates of Albany | Albany | New York | United States | 12208 |
Sponsors and Collaborators
- Navidea Biopharmaceuticals
Investigators
- Study Director: Cornelia Reininger, M.D., PhD, Navidea Biopharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NAV4-01