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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Navidea Biopharmaceuticals
ClinicalTrials.gov Identifier:
NCT01680588
First received: August 31, 2012
Last updated: November 26, 2013
Last verified: November 2013
  Purpose

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 Intervention Phase
Alzheimer Disease
Drug: [18F]NAV4694
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Navidea Biopharmaceuticals:

Primary Outcome Measures:
  • [18F]NAV4694 PET visual assessment by centralized readers [ Time Frame: 25 minutes post injection ] [ Designated as safety issue: No ]
    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 [ Time Frame: 7 Days ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 25 minutes post injection ] [ Designated as safety issue: No ]
    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 [ Time Frame: 25 minutes post injection ] [ Designated as safety issue: No ]
    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 [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 70
Study Start Date: August 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: [18F]NAV4694
Single intravenous injection of 8.1 millicuries of [18F]NAV4694
Drug: [18F]NAV4694

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01680588

Locations
United States, Connecticut
Molecular NeuroImaging, LLC
New Haven, Connecticut, United States, 06510
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
Alexian Brothers Neurosciences Institute
Elk Grove Village, Illinois, United States, 60007
United States, Indiana
Indiana Medical Research
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Brigham & Women's Hospital
Boston, Massachusetts, United States, 02115
Alzheimer's Disease Center, Quincy Medical Center
Quincy, Massachusetts, United States, 02169
United States, New York
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
  More Information

No publications provided

Responsible Party: Navidea Biopharmaceuticals
ClinicalTrials.gov Identifier: NCT01680588     History of Changes
Other Study ID Numbers: NAV4-01
Study First Received: August 31, 2012
Last Updated: November 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Navidea Biopharmaceuticals:
Alzheimer

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on April 14, 2014