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

Phase 1

Completed

• Conditions: Alzheimer Disease
• Interventions: Drug: [18F]THK-5351

• Registration Number: NCT03112096
• Lead Sponsor: Asan Foundation

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.

Detailed Description

This is a study to evaluate biodistribution, pharmacokinetics and safety of \[18F\]THK-5351 positron emission computed tomography. Ten cognitively healthy subjects and 10 patients with Alzheimer's Disease will be enrolled. The primary outcome measures are to evaluate pharmacokinetics of \[18F\]THK-5351 Positron Emission Tomography imaging . Tracer biodistribution will be evaluated by global and regional standardized uptake value ratio of \[18F\]THK-5351 in the brain. Safety. For safety assessment, a physical examination, Electrocardiogram and vital signs will be performed at baseline and at the completion of all imaging to assess for interval change.

Study Timeline

• Study First Submitted: 2017-03-26
• Study First Submitted QC: 2017-04-12
• Study First Posted: 2017-04-13
• Study Start: 2017-05-17
• Primary Completion: 2018-08-31
• Study Completion: 2018-08-31
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-11
• Last Update Posted: 2020-12-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

Not provided

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Exclusion Criteria

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

• General Exclusion Criteria 1. 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.

  2. 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.

  3. If the patient has or is suspicious of having a hypersensitivity or allergy to [18F] THK-5351 or its derivatives.

  4. The patient is pregnant, is attempting to become pregnant, or is nursing (breast-feeding) children.

  5. The patient has a history of alcoholism or drug dependency/abuse within the last 2 years before screening.

  6. 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.

  7. The patient has been treated with any investigational medicinal product (IMP) within 30 days prior to the screening visit.

  8. 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.

  9. The patient has been receiving an anti-cholinergic drug in a regular basis within 3 months prior to the screening visit.

  10. 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.

  11. The patients has disorders related to blood coagulation which could be inappropriate for arterial or venous sampling.

• Normal Subject Exclusion Criteria 1. The patient has evidence of a clinically significant medical disorder, neurological disorder, has an abnormal physical examination or abnormal laboratory evaluations from the screening visit, or has other abnormal findings that are clinically significant, as judged by the investigator.

  2. The patient has more than one direct family members who were diagnosed with Alzheimer's disease.

• Alzheimer's Disease Exclusion Criteria

  1. 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.
  2. The patient has more than two direct family members who were diagnosed with Alzheimer's disease.
  3. 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.
  4. The patient has received any of the treatments targeting tau protein prior to [18F]THK-5351 PET scan.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Alzheimer's Disease Subjects	[18F]THK-5351	Cognitively healthy subjects will receive an IV injection, \[18F\]THK-5351 injection
Cognitively Healthy Subjects	[18F]THK-5351	Cognitively healthy subjects will receive an IV injection, \[18F\]THK-5351 injection

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics: Maximum Serum Concentration (Cmax) of [18F]THK-5351	0-90 minutes post injection	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
Assess global and regional tau deposition as measured by standard uptake value ratio (SUVR) of [18F]THK-5351	0-90 minutes post injection or 50-70 minutes post injection	Compare Standard uptake value ratio (SUVR) and distribution of \[18F\]THK-5351 in cognitively healthy subjects and patients with Alzheimer's disease

Secondary Outcome Measures

Name	Time	Method
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	We will evaluate correlation between standard uptake value ratio (SUVR) and distribution volume of ratio(DVR) of\[18F\]THK-5351 positron emission computed tomography
Concentrations of metabolite in plasma of [18F]THK-5351	0-90 minutes post injection or 50-70 minutes post injection	Plasma metabolite concentrations \[18F\]THK-5351 will be assessed.
Number of participants with treatment related adverse events as a measure of safety	0-90 minutes post injection or 50-70 minutes post injection	For safety assessment, a physical examination, EKG and vital signs will be performed at baseline and at the completion of all imaging to assess for interval change.
Optimal scanning time for brain imaging using F-18 THK-5351.	0-90 minutes post injection	PET data will be acquired during a 90-min dynamic brain PET scan and will be started simultaneously with the injection of 10mCi of F-18 THK-5351. Reconstruction of PET imaging with several time frame will be compared.

Trial Locations

Locations (1)

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