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

An Open Label, Multicenter Study for Evaluation of the Clinical Utility of [18F]THK-5351 Positron Emission Computed Tomography in Cognitively Healthy Volunteers, Subjects With Mild Cognitive Impairment, Subjects With Alzheimer's Disease and Subjects With Other Neurodegenerative Diseases

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.

Study Overview

• Status: Completed
• Conditions: Neurodegenerative Diseases; Mild Cognitive Impairment; Alzheimer's Disease
• Intervention / Treatment: Drug: [18F]THK-5351

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cognitively Healthy Subjects; 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.	Drug: [18F]THK-5351; Imaging for evaluating the accumulation of abnormal tau protein in the brain; Other Names: FluoroTau
Experimental: MCI Subjects; MCI Subjects will receive an IV injection, [18F]THK-5351 at baseline and also receive an IV injection, [18F]THK-5351 at 24 months.	Drug: [18F]THK-5351; Imaging for evaluating the accumulation of abnormal tau protein in the brain; Other Names: FluoroTau
Experimental: AD Subjects; AD Subjects will receive an IV injection, [18F]THK-5351 at baseline and also receive an IV injection, [18F]THK-5351 at 24 months.	Drug: [18F]THK-5351; Imaging for evaluating the accumulation of abnormal tau protein in the brain; Other Names: FluoroTau
Experimental: Subjects with other neurodegenerative disease; Subjects with other neurodegenerative disease will receive an IV injection, [18F]THK-5351 at baseline.	Drug: [18F]THK-5351; Imaging for evaluating the accumulation of abnormal tau protein in the brain; Other Names: FluoroTau

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cross-sectional [18F]THK-5351 Imaging Results	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.	50-70 minutes post injection
Assess the rate of change of tau deposition as measured by [18F]THK-5351 uptake (SUVR) over time	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.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between standard uptake value ratio (SUVR) of [18F]THK-5351 positron emission computed tomography and neuropsychiatric test scores	We will evaluate correlation between standard uptake value ratio (SUVR) [18F]THK-5351 positron emission computed tomography and scores of neuropsychiatric test	50-70 minutes post-injection
Correlation between standard uptake value ratio (SUVR) of [18F]THK-5351 positron emission computed tomography and indices of structural MRI	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.	50-70 minutes post-injection
Correlation between standard uptake value ratio (SUVR) of [18F]THK-5351 positron emission computed tomography and indices of functional MRI	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.	50-70 minutes post-injection
Correlation between standard uptake value ratios (SUVR) and distribution of [18F]THK-5351 positron emission computed tomography and amyloid positron emission computed tomography	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	50-70 minutes post-injection

Collaborators and Investigators

• Sponsor: Jae Seung Kim
• Collaborators: Samsung Medical Center; Korea Health Industry Development Institute
• Investigators: Principal Investigator: Jae Seung Kim, M.D.,Ph.D., Asan Medical Center

Publications and helpful links

General Publications

• Chun MY, Lee J, Jeong JH, Roh JH, Oh SJ, Oh M, Oh JS, Kim JS, Moon SH, Woo SY, Kim YJ, Choe YS, Kim HJ, Na DL, Jang H, Seo SW. 18F-THK5351 PET Positivity and Longitudinal Changes in Cognitive Function in beta-Amyloid-Negative Amnestic Mild Cognitive Impairment. Yonsei Med J. 2022 Mar;63(3):259-264. doi: 10.3349/ymj.2022.63.3.259.
• Park JE, Yun J, Kim SJ, Shim WH, Oh JS, Oh M, Roh JH, Seo SW, Oh SJ, Kim JS. Intra-individual correlations between quantitative THK-5351 PET and MRI-derived cortical volume in Alzheimer's disease differ according to disease severity and amyloid positivity. PLoS One. 2019 Dec 13;14(12):e0226265. doi: 10.1371/journal.pone.0226265. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2016
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: January 12, 2016
• First Submitted That Met QC Criteria: January 13, 2016
• First Posted (Estimate): January 15, 2016

Study Record Updates

• Last Update Posted (Actual): December 14, 2020
• Last Update Submitted That Met QC Criteria: December 11, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Tau, neurodegeneration, positron emission computed tomography
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction; Neurodegenerative Diseases
• Other Study ID Numbers: THK-15002