A Longitudinal Evaluation of a Radiotracer for Use in Tau Tracking

NCT03919669 | Completed Phase 2 Results FDA Drug

• 4 other identifiers: 2018-1348A534255SMPH/MEDICINE/GER-AD DEVProtocol Version 8/26/2021
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This is a longitudinal, observational study evaluating the imaging characteristics of the tau PET radioligand \[18F\]MK-6240 in Alzheimer's disease (AD), Mild Cognitive Impairment (MCI) and Healthy Volunteer (HV) subjects. Up to 42 subjects, including approximately 28 MCI/mild AD subjects, up to 5 moderate AD subjects, and 9 similarly aged HV subjects will be consented and screened. Imaging procedures include \[11C\]PiB to evaluate amyloid deposition, \[18F\]MK-6240 PET, and structural MRI. All subjects complete an evaluable baseline \[18F\]MK-6240 PET scan, as well as scans at 6, 12 and 24 months post-baseline. If unable to complete the 6 month, 12 month, or 24 month visit, an 18 month and/or 30 month visit may instead be scheduled, totaling a maximum of four time points.

Conditions

Alzheimer Disease; Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• Change in [18F]MK-6240 Standard Uptake Value Ratio (SUVR) Uptake

  Composite mean SUVR across standard regions including: numerator was the entorhinal, amygdala, fusiform, inferior temporal, middle temporal cortex; denominator was the inferior cerebellum cortex. The SUVR is a ratio and has a theoretic interpretable minimum of 1.0. This primary outcome is reported by the three primary groups: Healthy Volunteers, Mild Cognitive Impairment, and Dementia.

  Baseline to 12 months

Secondary Outcomes (5)

• The Correlation Between the Change in [18F]MK-6240 Uptake and the Change in the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Using Items 1-11

  Baseline to 12 months

• Correlate the Changes in [18F]MK-6240 Uptake and Changes in Clinical Cognitive Assessments by Clinical Dementia Rating Scale (CDR).

  Baseline to 12 months

• Correlate the Changes in [18F]MK-6240 Uptake and Changes in Clinical Cognitive Assessments by Mini-Mental Status Exam (MMSE)

  Baseline to 12 months

• Change in [18F]MK-6240 Standard Uptake Value Ratio (SUVR) Uptake

  Baseline to 24 months

• Change in [18F]MK-6240 Standard Uptake Value Ratio (SUVR) Uptake

  Baseline to 6 months

Study Arms (1)

All Subjects

EXPERIMENTAL

All subjects will complete PET imaging sessions evaluating the tau PET radioligand \[18F\]MK-6240 at baseline, as well as at 6, 12 and 24 months post-baseline. If unable to complete the 6 month, 12 month, or 24 month visit, an 18 month and/or 30 month visit may instead be scheduled, totaling a maximum of four time points.

Drug: All Subjects

Interventions

All Subjects DRUG

All subjects will be given the experimental tau PET radioligand \[18F\]MK-6240

All Subjects

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated written informed consent must be obtained from the subject to enter the study and before any assessment is performed.
• Pregnancy: Participant is not pregnant at the time of the PET and MRI imaging exams. Urine pregnancy tests will be conducted as needed with pre-menopausal women who are of child-bearing potential.
• Willing and able to undergo study procedures and study schedule
• Availability of a study partner who has frequent and sufficient contact with the subject and is able to provide accurate information regarding the subject's cognitive and functional abilities for the CDR, agrees to accompany the subject and provide information at visits or is available by phone. The study partner must have sufficient cognitive capacity, in the judgment of the investigator, to accurately report upon the subject's behavior and cognitive and functional abilities.
• Healthy with no clinically relevant finding on physical examination at screening and upon reporting for the Baseline \[18F\]MK-6240 imaging visit.
• Normal Cognition based on cognitive results at screening.
• Healthy with no clinically relevant finding on physical examination at screening and upon reporting for the Baseline \[18F\]MK-6240 imaging visit.
• CDR global score =0
• Have screening \[11C\]PiB PET imaging demonstrating amyloid binding based on qualitative read or DVR index value \>1.20.
• MMSE score 26-30 (inclusive), CDR global score 0.5 for subjects with MCI
• MMSE score 22-26 (inclusive), CDR global score 0.5 or 1 for subjects with mild dementia due to AD
• MMSE score 16-21 (inclusive), CDR global score 1-2 for subjects with moderate dementia due to AD
• Subjects with MCI must meet 2018 research criteria for MCI (Jack et al., 2018).
• Subjects with dementia must meet 2018 research criteria for dementia (Jack et al., 2018).

You may not qualify if:

• Lack of capacity to provide informed consent at study entry.
• Subject has received an investigational drug or device within 30 days of screening. Other experimental PET radiotracer drugs are not excluded.
• For women, pregnant, lactating or breastfeeding or intention to become pregnant.
• Evidence of unstable or untreated clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, alternative neurological, immunodeficiency, pulmonary, or other disorder or disease. Stable, treated chronic medical conditions like hypertension, hypercholesterolemia, diabetes mellitus, non-metastatic dermatologic or prostatic cancer, etc. are acceptable as long as they do not, in the study investigator's opinion, contribute to cognitive dysfunction or limit participation in study procedures.
• Any illness or other consideration that makes it unlikely that the subject will be able to complete the 26-month study.
• Current or prior history (within past 5 years) of significant alcohol or substance abuse as determined by the investigator.
• Psychiatric disorders that may interfere with the study including current major Axis I DSM-V disorders including but not limited to severe Major depression, current or history of bipolar I disorder, or schizophrenia.
• Non-English speakers or subjects who are unable to comprehend study materials are excluded at entry
• MRI-incompatible implants or devices such as certain 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 that prevents completion of MRI protocol.
• Treatment with any therapeutic molecule that targets Aβ or tau within 12 months prior to screening.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Cerveau Technologies, Inc.: collaborator

Study Sites (1)

University of Wisconsin-Madison

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Limitations and Caveats

This study included a small sample size of 6 healthy volunteers, 8 Mild Cognitive Impairment, and 13 Dementia subjects. This limits the statistical conclusions of the study. The study subjects were all non-hispanic, white participants. This limits the generalizability of the results.

Results Point of Contact

• Title: Dr. Sterling Johnson
• Organization: University of WI Alzheimer's Disease Research Center

scj@medicine.wisc.edu

608-262-9549

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2019
• First Posted: April 18, 2019
• Study Start: April 2, 2019
• Primary Completion: May 19, 2022
• Study Completion: May 19, 2022
• Last Updated: August 3, 2023
• Results First Posted: August 3, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)