Aftobetin-HCl and Fluorescence Detection Measured by Sapphire II to Determine the Number and Timing of Administrations

Last updated: August 20, 2018
Sponsor: Cognoptix, Inc.
Overall Status: Active - Recruiting

Phase

1

Condition

Alzheimer's Disease

Memory Problems

Dementia

Treatment

N/A

Clinical Study ID

NCT02928211
PRT-0036
  • Ages 25-90
  • All Genders
  • Accepts Healthy Volunteers

Study Summary

This is an open-label study to evaluate Aftobetin-HCl and florescence detection as measured by the Sapphire II device.

Performance of Part I of the study has been completed (15 subjects received a single administration of Aftobetin HCL followed by Sapphire II measurements) and indicated that 3 administrations of Aftobetin-HCl are necessary. For Part II, a second group of up to 30 subjects (CN =10 and mild AD or MCI =20) will receive three Aftobetin HCL administrations. If three administrations of Aftobetin HCL are optimal, up to an additional 30 MCI and 30 mild AD subjects will be entered.

The purpose of the study as Part II is performed is to determine the ability of the Sapphire II device to detect B-amyloid in the lens of the eye in subjects with Mild Cognitive Impairment (MCI), and mild Alzheimer's Disease (AD) after three Aftobetin-HCl administrations. Subjects with Normal Cognition (CN) will also be tested to further establish that subjects who are highly unlikely to have B-amyloid deposits in the lens of the eye will have close to baseline post ligand fluorescent uptake value (FUV) using the Sapphire II technology.

Eligibility Criteria

Inclusion

For MCI and mild AD subjects:

  1. Aged 55-90 years old inclusive;

  2. Able to provide informed consent;

  3. Subject must have a reported memory concern verified by study partner (a study partneris someone willing to participate as a source of information and has at least weeklycontact with the subject);

  4. Capable of cooperating for the duration of the study with procedures and assessments;

  5. Magnetic Resonance Imaging (MRI) Scan within 9 months with:

  6. Modified Hachinski Score <4

  7. No evidence of infection, infarction (ischemic or hemorrhagic), or other focallesions (tumors, subdural hematomas, malformations, etc.)

  8. Geriatric Depression Scale (GDS) score of <6;

  9. Neuropsychiatric Inventory (NPI) total score <10 and <4 in any NPI domain;

  10. Sufficient vision in at least one eye and hearing to participate in cognitive testing For MCI subjects:

  11. Meets National Institute on Aging-Alzheimer's Association (NIA-AA) core clinicalcriteria for Mild Cognitive Impairment due to AD1;

  12. Clinical dementia Rating Scale Score (CDR) of 0.5 (memory box score must = 0.5);

  13. Mini-Mental State Exam (MMSE) score of >24;

  14. Abnormal memory function on education adjusted Wechsler Memory Scale Logical Memory IIsubscale (Delayed Paragraph Recall, Paragraph A only) - Revised (16 years: <11; 8-15years: <9; 0-7 years: <6);

  15. Absence of dementia: no significant impairment in cognitive functioning or Activitiesof Daily Living (AODLs) - Functional Assessment Questionaire (FAQ) score of <6. TheFAQ is answered by the study partner; For Mild AD subjects:

  16. Meets National Institute on Aging-Alzheimer's Association (NIA-AA) core clinicalcriteria for probable AD dementia2;

  17. CDR between 0.5 or 1;

  18. MMSE score between 20 to 26 (inclusive);

  19. Abnormal memory function on education adjusted Wechsler Memory Scale Logical Memory IIsubscale -(Delayed Paragraph Recall, Paragraph A only) -Revised (16 years: <8; 8-15years: <4; 0-7 years: <2);

  20. Functional Assessment Questionaire (FAQ) score of >6. The FAQ is answered by the studypartner; For CN subjects:

  21. Subject must be free of memory complaints;

  22. Cognitively normal, based on an absence of significant impairment in cognitivefunctions or activities of daily living;

  23. Normal memory function documented by scoring above education adjusted cut-offs on theLogical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from theWechsler Memory Scale - Revised (≥11 for 16 or more years of education; ≥9 for 8-15years of education;

  24. MMSE score of 29-30;

  25. CDR Scale Score of 0;

  26. Aged 25-40 years old inclusive; and

  27. Negative family history for onset of memory dysfunction in first or second degreerelatives before age 65.

Exclusion

Exclusion Criteria:

  1. Serious underlying medical disease which in the opinion of the investigator mayinterfere with the participant's ability to participate in the study such as unstablecardiac, pulmonary, renal, hepatic, endocrine, hematologic, active malignancy orinfectious disease;

  2. Non-AD causes of dementia that could cause impaired memory ruled out by standardizedwork up for dementia;

  3. Significant neurologic disease (e.g., Parkinson's Disease, Huntington's disease,normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizuredisorder, subdural hematoma, multiple sclerosis);

  4. Clinically relevant, abnormal serum chemistry, B12, TSH, and CBC <6 months of studyentry;

  5. History of significant head trauma followed by persistent neurologic defaults or knownstructural brain abnormalities, learning disability or mental retardation;

  6. Significant psychiatric illness in last year such as major depression, bipolar,obsessive compulsive or psychotic disorder;

  7. History of alcohol or substance abuse in last year;

  8. Pain or sleep disorder that could interfere with cognitive testing;

  9. Known hypersensitivity to Amyvid (Florbetapir-F 18) or any components of injectionformulation or contraindication to PET scan (e.g., pregnant, lactating, or ofchildbearing potential) in subjects requiring a PET scan.

  10. Receiving any investigational medications or participated in a trial withinvestigational medications within 30 days prior study entry;

  11. History of bilateral cataract surgery;

  12. Active ocular inflammation or infection;

  13. History of physical injury or other serious eye disease;

  14. Corneal disease that prevents visualization of the lens, e.g, Fuch's dystrophy orkeratokonus;

  15. Inability to tolerate the PET environment, e.g., due to physical size and/orclaustrophobia in subjects requiring a PET scan.

  16. Serious suicidal ideation in the opinion of the investigator or answers 'yes' to Item 4 or 5 on the Columbia Suicide Severity Rating Scale (CSSRS) at screening;

  17. Inability to undergo MRI procedure (e.g., metal implant, metallic devices, e.g.,non-MRI-safe cardiac pacemaker or neuro-stimulator, some artificial joints, metalpins, surgical clips, other implanted metal, or claustrophobia or discomfort inconfined spaces)

  18. May not be taking any of the following psychoactive medications:

  • Regular use narcotic analgesics (>2 doses/ week)

  • Clonidine, neuroleptics, antidepressants with central anticholinergic activity

  • Other agents with central anticholinergic activity such as diphenhydramine,hydroxyzine, benztropine

  • Diazepam, clonazepam, temazepam, chlordiazepoxide, or triazolam Note: it is permitted to remain on the following psychoactive medications provided thesubject has been receiving them for greater than or equal to 4 weeks:

  • Antidepressants lacking significant anticholinergic side effects

  • Estrogen replacement therapy

  • Gingko biloba

  • Sedative hypnotics: lorazepam, buspirone, oxazepam, zolpidem, zaleplon, alprazolam,chloral hydrate Note: it is permitted to remain on the following psychoactive medications provided thesubject has been receiving them for greater than or equal to 12 weeks:

  • Cholinesterase inhibitors

  • Memantine Note: the washout from psychoactive medication (e.g., excludedantidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics) must be atleast 4 weeks prior to screening.

Study Design

Total Participants: 105
Study Start date:
July 01, 2016
Estimated Completion Date:
January 31, 2019

Study Description

Open label study. 45-105 subjects will be enrolled.

Subjects will undergo the following procedures:

  • Complete physical and neurologic examination (Screening)

  • Neuropsychological testing (Screening)

  • Ophthalmologic examination (Screening and Visit 4 (Safety follow up visit))

  • Administration of ointment - 3 administrations (Visit 1)

  • Sapphire II Fluorescent Eye Measurements (Visits 1-3): Prior to first administration of ointment and then 24 +/- 2 hours, 28 +/- 30 minutes and 48 +/- 2 hours following first ointment administration

  • Amyvid Positron Emission Tomography (PET) Amyloid Scan (only required for MCI and mild AD subjects who have not had a positive amyloid PET scan in the last 3 years)

Subjects will also be asked to participate in an elective second Sapphire II assessment to assess its reproducibility. Repeatability testing is optional and will require a separate consent. Subjects will come back for Visits 5-9 (ointment administration and eye scans and a follow up safety assessment).

Connect with a study center

  • Neurology Research Institute

    West Palm Beach, Florida 33407
    United States

    Active - Recruiting

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