Phase 1 Evaluation of [18F]MK-6240 PET as an Imaging Marker for Tau Protein

NCT ID: NCT03071224

Last Updated: 2021-06-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2021-06-09

Brief Summary

The overall goal of this protocol is to evaluate [18F]MK-6240 (also known as [18F]MNI-946) a tau targeted radiopharmaceutical.

Detailed Description

The overall goal of this protocol is to evaluate [18F]MK-6240 (also known as [18F]MNI-946) a tau targeted radiopharmaceutical.

• To measure the dynamic uptake and washout of [18F]MK-6240 in brain using positron emission tomography (PET) in patients with Alzheimer's disease and healthy volunteers.
• To measure blood metabolites of [18F]MK-6240 and perform kinetic modeling to assess its ability to measure tau protein in brain using the tracer plasma concentration or a reference region as indirect input.
• To obtain test/retest reliability of the tracer binding parameters in patients with Alzheimer's disease and healthy volunteers (Cohort 1).
• To acquire safety data following injection of [18F]MK-6240.
• To determine the longitudinal change in tau burden (including SUVR and tau distribution metrics) compared to baseline in AD subjects and in similarly aged HV subjects.
• To evaluate the correlation between the longitudinal change in tau burden and change in clinical, MRI and CSF biomarker measures in AD subjects and in similarly-aged HV subjects.
• To further explore the relationship between tracer metabolism and smoking (Cohort 3).

Conditions

Alzheimer Disease; Healthy Volunteers

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

[18F]MNI-946

To evaluate \[18F\]MK-6240 (also known as \[18F\]MNI-946) a tau targeted radiopharmaceutical.

Group Type: EXPERIMENTAL

[18F] MNI-946

Intervention Type: DRUG

Subjects will undergo PET imaging using \[18F\]MNI-946, a PET radioligand for imaging tau.

[18F]Florbetapir

Intervention Type: DRUG

Subjects with Alzheimer's disease will receive a \[18F\]florbetapir scan to compare distribution of tau in the brain compared to that of \[18F\]MNI-946.

Interventions

[18F] MNI-946

Subjects will undergo PET imaging using \[18F\]MNI-946, a PET radioligand for imaging tau.

Intervention Type: DRUG

[18F]Florbetapir

Subjects with Alzheimer's disease will receive a \[18F\]florbetapir scan to compare distribution of tau in the brain compared to that of \[18F\]MNI-946.

Intervention Type: DRUG

Other Intervention Names

[18F]MK6240

Eligibility Criteria

Inclusion Criteria

• Written informed consent must be obtained before any assessment is performed.
• Female subjects must be documented by medical records or physician's note to be either surgically sterile (by means of hysterectomy, bilateral oophorectomy, or tubal ligation) or post-menopausal for at least 1 year or, if they are of child-bearing potential, must commit to use two methods of contraception, one of which is a barrier method for the duration of the study.
• Male subjects and their partners of childbearing potential must commit to the use of two methods of contraception, one of which is a barrier method for male subjects for the study duration.
• Male subjects must not donate sperm for the study duration.
• Willing and able to cooperate with study procedures.

• Males and females aged ≥50 years. Healthy with no clinically relevant finding on physical examination at screening and upon reporting for the [18F]MK-6240 imaging visit.
• No cognitive impairment from neuropsychological battery as judged by the investigator
• Have screening [18F]Florbetapir PET imaging demonstrating no significant amyloid binding based on qualitative (visual read).
• No family history of Alzheimer's disease or neurological disease associated with dementia
• Have a CDR global score=0
• Have an MMSE score ≥28
• Willing and able to cooperate with study procedures.

• Males and females aged 50 to 80 years.
• Have probable Alzheimer's disease dementia, based on the NINCDS/ADRDA and DSM-IV criteria, with mild severity and amnestic presentation
• Have a CDR score ≥ 0.5 at screening
• Have a MMSE score between ≤26 .
• Have screening [18F]Florbetapir or prior (in the last 12 months) amyloid PET imaging demonstrating amyloid binding based on qualitative (visual read).[18F]Florbetapir PET imaging results will be shared with participants and scans may be used by participants for future research use.
• A brain MRI that supports a diagnosis of AD, with no evidence of significant neurologic pathology.
• Medications taken for symptomatic treatment of AD must be maintained on a stable dosage regimen for at least 30 days before screening visit.
• Signed and dated written informed consent obtained from the subject and the subject's legally authorized representative or caregiver (if applicable).
• The subject has an appropriate caregiver capable of accompanying subject on all visits, if necessary.

• Subjects must be active smokers at the time of initial consent

Exclusion Criteria

• Current or prior history of any alcohol or drug abuse.
• Laboratory tests with clinically significant abnormalities and/or clinically significant unstable medical illness.
• Subject has received an investigational therapeutic drug or device within 30 days of screening.
• Prior participation in other research protocols or clinical care in the last year in addition to the radiation exposure expected from participation in this clinical study, such that radiation exposure exceeds the effective dose of 50 mSv, which would be above the acceptable annual limit established by the US Federal Guidelines.
• Pregnancy, lactating or breastfeeding.
• Evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, alternative neurological, immunodeficiency, pulmonary, or other disorder or disease.
• Unsuitable veins for repeated venipuncture.
• Implants such as implanted cardiac pacemakers or defibrillators, insulin pumps, cochlear implants, metallic ocular foreign body, implanted neural stimulators, CNS aneurysm clips and other medical implants that have not been certified for MRI, or history of claustrophobia in MRI.

• Has received treatment that targeted Aβ or tau within the last 3 months.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Invicro

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Russell, M.D., Ph. D

Role: PRINCIPAL_INVESTIGATOR

Invicro

Locations

Invicro

New Haven, Connecticut, United States

Countries

United States

Related Links

http://invicro.com/

Related Info

Other Identifiers

[18F] MNI-946

Identifier Type: -

Identifier Source: org_study_id