[18F]THK-5351 Positron Emission Computed Tomography Study of Normal, Mild Cognitive Impairment, Alzheimer's Disease and Other Neurodegenerative Disease

Phase 2

Completed

• Conditions: Alzheimer's Disease; Mild Cognitive Impairment; Neurodegenerative Diseases
• Interventions: Drug: [18F]THK-5351

• Registration Number: NCT02656498
• Lead Sponsor: Jae Seung Kim

Brief Summary

This is a cross-sectional and longitudinal study to evaluate the clinical utility of \[18F\]THK-5351 positron emission computed tomography in cognitively healthy volunteers, mild cognitive impairment (MCI), Alzheimer's disease (AD) and other neurodegenerative patients.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-01-11
• Study First Submitted: 2016-01-12
• Study First Submitted QC: 2016-01-13
• Study First Posted: 2016-01-15
• Primary Completion: 2019-12-31
• Study Completion: 2019-12-31
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-11
• Last Update Posted: 2020-12-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 135

Inclusion Criteria

1. General Subject Inclusion Criteria

   In order to be eligible for participation in this trial, the subject must:

   • Be ≥ 40 and < 80 years of age at the Screening Visit.
   • Be able to read at a 6th grade level or equivalent, (as determined by the investigator, and must have a history of academic achievement and/or employment sufficient to exclude mental retardation.)
   • Be able to speak, read, hear, and understand the language of the trial staff, and the informed consent form, and possess the ability to respond verbally to questions, follow instructions, and complete questionnaires and detailed neuropsychological test.
   • Have results of clinical laboratory tests/physical examination, vital signs, and ECG within normal limits (at 90 days prior to [18F]THK-5351 positron emission computed tomography) or clinically acceptable to the investigator at screening.
   • Be able to possess the ability to respond verbally to questions, follow instructions, and underwent research assessment, including brain images based on the investigator's judgment. Each subject is also able and willing to adhere visit schedules.
   • If female, not be of childbearing potential as indicated by one of the following
   • Each subject (or legal representative) must sign the informed consent form in accordance with local requirements after the scope and nature of the investigation have been explained to them, and before screening assessments.
   • Each subject must be willing to provided blood samples for genotyping apolipoprotein E

2. Cognitively Healthy Subjects

3. MCI Subjects

4. AD Subjects

5. Subjects with other neurodegenerative disease

Exclusion Criteria

The subject must be excluded from participating in the trial if the subject fulfil any single criteria described below:

1. General Exclusion Criteria

• Based on the investigators' judgement, if the patient is not capable of communicating with the site personnel, if the patient is not proficient in the language in which the psychometric tests will be completed, or if the patient is not sufficient for compliance with the study procedures.
• The patient has an abnormal physical examination or abnormal laboratory test results at the screening that are clinically significant to affect results of the research, as judged by the investigator.
• If the patient has or is suspicious of having a hypersensitivity or allergy to [18F] THK-5351 or its derivatives.
• The patient is pregnant, is attempting to become pregnant, or is nursing (breast-feeding) children.
• The patient has a history of alcoholism or drug dependency/abuse within the last 2 years before screening.
• The patient has contraindications to undergo positron emission computed tomography or MRI, which include but are not restricted to the examples below: claustrophobia, cardiac pacemaker, metal devices around the eye or spinal cord, cochlear implant, etc.) at the screening visit.
• The patient has been treated with any investigational medicinal product (IMP) within 30 days prior to the screening visit.
• The patient has been tested positive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), HIV Antibody, or syphilis serum test at the screening visit.
• The patient has been receiving an anti-cholinergic drug in a regular basis within 3 months prior to the screening visit.
• The patient has evidence of a clinically relevant neurological disorders other than the disease being studied (i.e., prodromal AD) at screening, including but not limited to: territorial cerebral infarction, intracranial hemorrhage, multiple sclerosis, neurosyphilis, mental retardation, hypoxic encephalopathy, major head trauma with loss of consciousness that led to persistent cognitive deficits.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cognitively Healthy Subjects	[18F]THK-5351	Cognitively healthy subjects will receive an IV injection, \[18F\]THK-5351 at baseline and also receive an IV injection, \[18F\]THK-5351 at 24 months.
Subjects with other neurodegenerative disease	[18F]THK-5351	Subjects with other neurodegenerative disease will receive an IV injection, \[18F\]THK-5351 at baseline.
MCI Subjects	[18F]THK-5351	MCI Subjects will receive an IV injection, \[18F\]THK-5351 at baseline and also receive an IV injection, \[18F\]THK-5351 at 24 months.
AD Subjects	[18F]THK-5351	AD Subjects will receive an IV injection, \[18F\]THK-5351 at baseline and also receive an IV injection, \[18F\]THK-5351 at 24 months.

Primary Outcome Measures

Name	Time	Method
Cross-sectional [18F]THK-5351 Imaging Results	50-70 minutes post injection	Compare Standard uptake value ratio (SUVR) and distribution of \[18F\]THK-5351 in subjects with MCI, subjects with AD, subjects with other neurodegenerative disease and cognitively healthy individuals.
Assess the rate of change of tau deposition as measured by [18F]THK-5351 uptake (SUVR) over time	24 months	Compare Standard uptake value ratio (SUVR) and distribution of \[18F\]THK-5351 in subjects with MCI, subjects with AD, subjects with other neurodegenerative disease and cognitively healthy individuals.

Secondary Outcome Measures

Name	Time	Method
Correlation between standard uptake value ratio (SUVR) of [18F]THK-5351 positron emission computed tomography and neuropsychiatric test scores	50-70 minutes post-injection	We will evaluate correlation between standard uptake value ratio (SUVR) \[18F\]THK-5351 positron emission computed tomography and scores of neuropsychiatric test
Correlation between standard uptake value ratio (SUVR) of [18F]THK-5351 positron emission computed tomography and indices of structural MRI	50-70 minutes post-injection	We will evaluate correlation between standard uptake value ratio (SUVR) \[18F\]THK-5351 positron emission computed tomography and indices of structural MRI including cortical thickness, hippocampal atrophy.
Correlation between standard uptake value ratio (SUVR) of [18F]THK-5351 positron emission computed tomography and indices of functional MRI	50-70 minutes post-injection	We will evaluate correlation between standard uptake value ratio (SUVR) \[18F\]THK-5351 positron emission computed tomography and indices of functional MRI derived from diffusion tensor imaging and resting state functional MRI.
Correlation between standard uptake value ratios (SUVR) and distribution of [18F]THK-5351 positron emission computed tomography and amyloid positron emission computed tomography	50-70 minutes post-injection	We will evaluate correlation between standard uptake value ratio (SUVR) and distribution of \[18F\]THK-5351 positron emission computed tomography and those of amyloid positron emission computed tomography

Trial Locations

Locations (2)

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of