Efficacy and Safety of the PET Imaging Agent [18F]NAV4694 in Subjects With Probable Alzheimer's Disease

Alzheimer Disease Clinical Trial

Official title:

A Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of [18F]NAV4694 PET in the Detection of Beta Amyloid in Subjects With Probable Alzheimer's Disease, Older Healthy Volunteers, and Young Healthy Volunteers

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01680588
• Other study ID #: NAV4-01
• Status: Active, not recruiting
• Phase: Phase 2
• First received: August 31, 2012
• Last updated: March 29, 2016
• Start date: August 2012
• Est. completion date: December 2018

Study information

• Verified date: March 2016
• Source: Navidea Biopharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 70
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• [18F]NAV4694

Locations

Country	Name	City	State
United States	Neurological Associates of Albany	Albany	New York
United States	Brigham & Women's Hospital	Boston	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
United States	Alexian Brothers Neurosciences Institute	Elk Grove Village	Illinois
United States	Indiana Medical Research	Indianapolis	Indiana
United States	Molecular NeuroImaging, LLC	New Haven	Connecticut
United States	Alzheimer's Disease Center, Quincy Medical Center	Quincy	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Navidea Biopharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	[18F]NAV4694 PET visual assessment by centralized readers	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.	25 minutes post injection	No
Secondary	Assess the incidence of adverse events after a single dose of [18F]NAV4694	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.	7 Days	Yes
Secondary	Evaluate [18F]NAV4694 PET quantitative assessment	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.	25 minutes post injection	No
Secondary	Determine correlation of neuro-psychiatric tests with [18F]NAV4694 imaging	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	25 minutes post injection	No
Secondary	Assess changes in laboratory values after a single dose of [18F]NAV4694	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.	7 days	Yes