A Phase I [18F]THK-5351 Positron Emission Tomography Study in Healthy Subjects and Alzheimer's Disease

NCT03112096 | Completed Phase 1

• 1 other identifier: THK-15001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study to evaluate biodistribution, pharmacokinetics and safety of \[18F\]THK-5351 positron emission computed tomography in Cognitively Healthy Subjects and Patients with Alzheimer's Disease.

Conditions

Alzheimer Disease

Keywords

Tau; neurodegeneration; positron emission tomography

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetics: Maximum Serum Concentration (Cmax) of [18F]THK-5351

  Compare time activity curve and calculate maximum serum concentration (Cmax) of each region of interest of \[18F\]THK-5351 positron emission computed tomography in cognitively healthy subjects and patients with Alzheimer's disease

  0-90 minutes post injection

• Assess global and regional tau deposition as measured by standard uptake value ratio (SUVR) of [18F]THK-5351

  Compare Standard uptake value ratio (SUVR) and distribution of \[18F\]THK-5351 in cognitively healthy subjects and patients with Alzheimer's disease

  0-90 minutes post injection or 50-70 minutes post injection

Secondary Outcomes (4)

• Correlation between standard uptake value ratio (SUVR) and distribution volume of ratio(DVR) of [18F]THK-5351 positron emission computed tomography

  0-90 minutes post injection or 50-70 minutes post injection

• Optimal scanning time for brain imaging using F-18 THK-5351.

  0-90 minutes post injection

• Concentrations of metabolite in plasma of [18F]THK-5351

  0-90 minutes post injection or 50-70 minutes post injection

• Number of participants with treatment related adverse events as a measure of safety

  0-90 minutes post injection or 50-70 minutes post injection

Study Arms (2)

Cognitively Healthy Subjects

EXPERIMENTAL

Cognitively healthy subjects will receive an IV injection, \[18F\]THK-5351 injection

Drug: [18F]THK-5351

Alzheimer's Disease Subjects

EXPERIMENTAL

Cognitively healthy subjects will receive an IV injection, \[18F\]THK-5351 injection

Drug: [18F]THK-5351

Interventions

[18F]THK-5351 DRUG

Imaging for evaluating the biodistribution, pharmacokinetics and safety of abnormal tau protein in the brain

Also known as: FluoroTau

Alzheimer's Disease Subjects; Cognitively Healthy Subjects

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible for participation in this trial, the subject must:
• 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 Electrocardiogram within normal limits (at 45 days prior to \[18F\]THK-5351 Positron Emission Tomography scan ) 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
• has reached natural menopause, defined as ≥ 24 months of spontaneous amenorrhea or
• has had a hysterectomy; or
• has had a bilateral oophorectomy (with or without a hysterectomy) and more than 6 weeks have passed since the surgery.
• 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.
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• Be ≥ 20 years of age at the screening visit
• Each subject must not report a history of memory decline with gradual onset and slow progression, that is either corroborated by an informant who knows the subject well or is documented in medical records. Each subject must have general cognitive function and activities of daily living sufficiently intact, based on clinical assessment, so as not to meet criteria for mild AD dementia (based on DSM-IV-TR(Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) and NINCDS-ADRDA(National Institute of Neurological and Communicative Disorders and Stroke; Alzheimer's Disease and Related Disorders Association) criteria).
• Each subject must have results of Korean-Mini Mental State Exam (K-MMSE) at screening that is ≥1.5 SD above the appropriate population mean, corrected age and education.
• Each subject must not have objective impairment in memory at screening that is ≥1.5 SD above the appropriate population mean, corrected age and education, as measured by the Seoul Verbal Learning Test (SVLT) delayed recall score of the Seoul Neuropsychological Screening Battery (SNSB)-Ⅱ.

You may not qualify if:

• The subject must be excluded from participating in the trial if the subject fulfil any single criteria described below:
• \. The patient has an abnormal physical examination, abnormal laboratory test or electrocardiography 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 PET 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.
• \. The patients has disorders related to blood coagulation which could be inappropriate for arterial or venous sampling.
• \. The patient has more than one direct family members who were diagnosed with Alzheimer's disease.
• The patient has evidence of any clinically significant neurodegenerative disease, or other serious neurological disorders other than AD including but not limited to stroke, traumatic brain injury, non-Alzheimer tauopathy, Parkinson's disease, or has evidence of a clinically relevant or unstable psychiatric disorders, including but not limited to major depression, schizophrenia, or bipolar disorder.
• The patient has more than two direct family members who were diagnosed with Alzheimer's disease.
• The patient has a stroke or an evidence of significant cerebrovascular disease from screening imaging scan that is clinically important in the investigator's opinion.

Sponsors & Collaborators

• Asan Foundation: lead

Study Sites (1)

Asan Medical Center

Seoul, 05505, South Korea

Location

MeSH Terms

Conditions

Alzheimer Disease; Pick Disease of the Brain; Nerve Degeneration

Interventions

THK5351

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Frontotemporal Dementia; Frontotemporal Lobar Degeneration; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• JaeEun Kim

  Asan Foundation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2017
• First Posted: April 13, 2017
• Study Start: May 17, 2017
• Primary Completion: August 31, 2018
• Study Completion: August 31, 2018
• Last Updated: December 14, 2020

Record last verified: 2020-12

Locations

KR (1)