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

NCT02928211 | Unknown Phase 1

• 1 other identifier: PRT-0036
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Mild Cognitive Impairment; Alzheimer's Disease

Outcome Measures

Primary Outcomes (3)

• Paired pre-ligand and post ligand fluorescent uptake values (FUV)

  through study completion, approximately 4 weeks

• Determination of success (yes or no)

  Determination of success (yes or no) associated with FUVs obtained after one dose or two doses of ligand at each time point by subject

  through study completion, approximately 4 weeks

• The overall diagnostic precision for each combination of Aftobetin-HCl administrations and Fluorescent Uptake Value (FUV)

  The overall diagnostic precision for each combination of: * The number of Aftobetin-HCl administrations and * Fluorescent Uptake Value (FUV): amyloid binding of Aftobetin-HCl to the lens of the eye as measured by Sapphire II system at 1, 2, 3, 4, 5, 6 (+/-10 minutes) and 24 hour (+/- 2 hours) time points for Part I and * Fluorescent Uptake Value (FUV): amyloid binding of Aftobetin-HCl to the lens of the eye as measured by Sapphire II system at 24 hours (+/-2 hours), 28 hours (+/- 30 minutes) and 48 hours (+/- 2 hours) for Part II.

  through study completion, approximately 4 weeks

Secondary Outcomes (5)

• Estimates of sensitivity and specificity of MCI and mild AD subjects compared to cognitively normal subjects

  through study completion, approximately 4 weeks

• Safety of Sapphire II procedure as determined by instances of Adverse Events

  through the follow up safety visit, approximately 4 weeks

• Characterization of maximal fluorescence after 1, or potentially 3, ointment administrations

  through study completion, approximately 4 weeks

• Intra-class correlation of the repeatability of the Sapphire II measurements to verify the system's reliability for reproducible results

  through study completion, approximately 6 weeks

• Correlation of FUV to PET amyloid status

  through study completion, approximately 4 weeks

Study Arms (1)

Experimental

EXPERIMENTAL

All subjects will receive the ointment and have scans with the Sapphire II device

Device: Sapphire II; Drug: Aftobetin-HCl; Radiation: Positron Emission Tomography

Interventions

Sapphire II DEVICE

A Class 1 laser device used in conjunction with the ointment to measure fluorescence emissions from the anterior segment (lens) of the eye.

Experimental

Aftobetin-HCl DRUG

The medical imaging agent (the ointment), Aftobetin-HCl is an amyloid binding ligand formulated into an ophthalmic ointment.

Also known as: medical imaging agent, ointment

Experimental

Positron Emission Tomography RADIATION

Amyvid 370 MBq (10 mCi) is administered as a single bolus through a short intravenous catheter in a total volume of 10 mL.

Also known as: PET

Experimental

Eligibility Criteria

• Age: 25 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Serious underlying medical disease which in the opinion of the investigator may interfere with the participant's ability to participate in the study such as unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, active malignancy or infectious disease;
• Non-AD causes of dementia that could cause impaired memory ruled out by standardized work up for dementia;
• Significant neurologic disease (e.g., Parkinson's Disease, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis);
• Clinically relevant, abnormal serum chemistry, B12, TSH, and CBC \<6 months of study entry;
• History of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities, learning disability or mental retardation;
• Significant psychiatric illness in last year such as major depression, bipolar, obsessive compulsive or psychotic disorder;
• History of alcohol or substance abuse in last year;
• Pain or sleep disorder that could interfere with cognitive testing;
• Known hypersensitivity to Amyvid (Florbetapir-F 18) or any components of injection formulation or contraindication to PET scan (e.g., pregnant, lactating, or of childbearing potential) in subjects requiring a PET scan.
• Receiving any investigational medications or participated in a trial with investigational medications within 30 days prior study entry;
• History of bilateral cataract surgery;
• Active ocular inflammation or infection;
• History of physical injury or other serious eye disease;
• Corneal disease that prevents visualization of the lens, e.g, Fuch's dystrophy or keratokonus;
• Inability to tolerate the PET environment, e.g., due to physical size and/or claustrophobia in subjects requiring a PET scan.

Sponsors & Collaborators

• Cognoptix, Inc.: lead

Study Sites (1)

Neurology Research Institute

West Palm Beach, Florida, 33407, United States

RECRUITING

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease

Interventions

Ointments; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Joyce Myers, MD

  Cognoptix, Inc.

  STUDY DIRECTOR

Central Study Contacts

Dennis Nilan

CONTACT

(978) 263-0005; info@cognoptix.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2016
• First Posted: October 10, 2016
• Study Start: July 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: January 1, 2019
• Last Updated: August 22, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share

Locations

US (1)