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

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

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.

Study Overview

• Status: Unknown
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: [18F]NAV4694

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Molecular NeuroImaging, LLC
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Elk Grove Village, Illinois, United States, 60007
      • Alexian Brothers Neurosciences Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana Medical Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital
    • Quincy, Massachusetts, United States, 02169
      • Alzheimer's Disease Center, Quincy Medical Center
  • New York
    • Albany, New York, United States, 12208
      • Neurological Associates of Albany

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [18F]NAV4694; Single intravenous injection of 8.1 millicuries of [18F]NAV4694	Drug: [18F]NAV4694

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: Navidea Biopharmaceuticals
• Investigators: Study Director: Cornelia Reininger, M.D., PhD, Navidea Biopharmaceuticals

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: August 31, 2012
• First Submitted That Met QC Criteria: September 4, 2012
• First Posted (Estimate): September 7, 2012

Study Record Updates

• Last Update Posted (Estimate): March 30, 2016
• Last Update Submitted That Met QC Criteria: March 29, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Alzheimer
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: NAV4-01