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NCT02562989

[18F]MK-6240 Positron Emission Tomography (PET) Tracer First-in-Human Validation Study (MK-6240-001)

Completed Phase 1 Results posted Last updated 18 September 2018
What this trial tests

Phase 1 trial testing [18F]MK-6240, ~185 MBq in Alzheimer's Disease in 13 participants. Completed in 27 December 2016.

Timeline
19 October 2015
Primary endpoint
27 December 2016
27 December 2016

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposediagnostic
Enrollment13
Start date19 October 2015
Primary completion27 December 2016
Estimated completion27 December 2016

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 18 to 85, any sex, with Alzheimer's Disease or Amnestic Mild Cognitive Impairment. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Adverse Events (AEs) Primary · Part 1: Up to 5 weeks; Part 2: up to 16 weeks

The number of participants experiencing an adverse event (AE) was monitored. An AE is any unfavorable and unintended medical occurrence, symptom, or disease witnessed in a participant, regardless of whether or not a causal relationship with the study treatment can be demonstrated. Further, any worsening of a preexisting condition that is temporally associated with the use of the study treatment is also considered an AE.

GroupValue95% CI
Part 1, Healthy Young Participants1
Part 2, Healthy Elderly Participants3
Part 2, AD and Amnestic MCI Elderly Participants2
Number of Participants Who Discontinued Study Due to an AE Primary · Part 1: Up to 5 weeks; Part 2: up to 16 weeks

The number of participants discontinuing study due to an AE was monitored.

GroupValue95% CI
Part 1, Healthy Young Participants0
Part 2, Healthy Elderly Participants0
Part 2, AD and Amnestic MCI Elderly Participants0
Effective Dose of [18F]MK-6240 Primary · Up to approximately 5 hours following [18F]MK-6240 administration

Mean effective dose (ED) of \[18F\]MK-6240 was calculated from whole-body (WB) PET scans of healthy young participants included in Part 1 of study. ED, reported as microsieverts (µSv) / megabecquerel (MBq), is a measure of WB radiation exposure risk that accounts for differences in individual organ exposure and organ susceptibility to ionizing radiation. Following \[18F\]MK-6240 PET tracer administration, organ-specific time-activity curves (TACs) and radioactivity residence times were utilized to calculate exposure risk for individual organs. These values calculated for individual organs were

GroupValue95% CI
Part 1, Healthy Young Participants29.4± 0.6
Organ Effective Dose of [18F]MK-6240 Primary · Up to approximately 5 hours following [18F]MK-6240 administration

Mean organ ED of \[18F\]MK-6240 was calculated from WB PET scans of healthy young participants included in Part 1 of study. Organ ED, reported as micrograys (µGy) / MBq, is a measure of organ-specific radiation exposure risk. Following \[18F\]MK-6240 PET tracer administration, organ-specific TACs and radioactivity residence times were utilized to calculate organ ED for specific organs of the body.

Adrenals
GroupValue95% CI
Part 1, Healthy Young Participants12.7± 1.0
Brain
GroupValue95% CI
Part 1, Healthy Young Participants8.8± 0.4
Breasts
GroupValue95% CI
Part 1, Healthy Young Participants5.8± 0.9
Gallbladder Wall
GroupValue95% CI
Part 1, Healthy Young Participants202.0± 111.0
Lower Large Intestine Wall
GroupValue95% CI
Part 1, Healthy Young Participants46.4± 5.5
Small Intestine
GroupValue95% CI
Part 1, Healthy Young Participants116.0± 13.3
Stomach Wall
GroupValue95% CI
Part 1, Healthy Young Participants16.9± 3.7
Upper Large Intestine Wall
GroupValue95% CI
Part 1, Healthy Young Participants128.0± 15.7
Standardized Uptake Value Ratio (SUVR) of [18F]MK-6240 in Brain Regions of Interest Primary · From 60 to 90 minutes following [18F]MK-6240 administration

As a surrogate of regional \[18F\[MK-6240 tracer distribution volume (VT), mean standardized uptake value ratios (SUVRs), were calculated for specific brain regions of interest (ROIs) in healthy elderly as well as AD/MCI elderly participants in Part 2 of the study. Calculated using calibrated PET scan images from each participant, SUVR is the relative ratio of pixel intensities at a specific brain ROI compared to a reference region (RR; cerebellar cortex, for this study). For an individual participant, the average SUVR for each brain ROI is calculated starting at 60 minutes and ending at 90 mi

Frontal Lobe
GroupValue95% CI
Part 2, Healthy Elderly Participants0.95± 0.07
Part 2, AD and Amnestic MCI Elderly Participants1.22± 0.47
Temporal Lobe
GroupValue95% CI
Part 2, Healthy Elderly Participants0.98± 0.07
Part 2, AD and Amnestic MCI Elderly Participants1.64± 0.72
Parietal Lobe
GroupValue95% CI
Part 2, Healthy Elderly Participants0.95± 0.06
Part 2, AD and Amnestic MCI Elderly Participants1.42± 0.80
Occipital Lobe
GroupValue95% CI
Part 2, Healthy Elderly Participants1.01± 0.06
Part 2, AD and Amnestic MCI Elderly Participants1.61± 0.92
Insula and Cingulate Cortex
GroupValue95% CI
Part 2, Healthy Elderly Participants0.93± 0.07
Part 2, AD and Amnestic MCI Elderly Participants1.22± 0.42
Hippocampus
GroupValue95% CI
Part 2, Healthy Elderly Participants0.93± 0.10
Part 2, AD and Amnestic MCI Elderly Participants1.37± 0.25
Amygdala
GroupValue95% CI
Part 2, Healthy Elderly Participants0.84± 0.11
Part 2, AD and Amnestic MCI Elderly Participants1.67± 0.40
Parahippocampal and Ambient Gyri
GroupValue95% CI
Part 2, Healthy Elderly Participants0.96± 0.11
Part 2, AD and Amnestic MCI Elderly Participants1.71± 0.39
Intra-subject Test-Retest (T-RT) Variability of Standardized Uptake Value Ratio (SUVR) in Brain Regions of Interest Primary · Up to 16 weeks following initial dose of [18F]MK-6240

For each AD/MCI participant receiving 2 doses of MK-6240, the SUVR (60-90 min) during initial dose (SUVR\_1) was compared to the SUVR (60-90 min) during the second dose (SUVR\_2) to determine the percent test-retest (T-RT) variability of the SUVR (60-90 min) for each brain ROI. T-RT variability = (absolute value (SUVR\_1 - SUVR\_2) / average SUVR) \* 100. If T-RT variability = 0, indicates no variability between SUVR\_1 and SUVR\_2.

Frontal Lobe
GroupValue95% CI
Part 2, AD and Amnestic MCI Elderly Participants7
Temporal Lobe
GroupValue95% CI
Part 2, AD and Amnestic MCI Elderly Participants12
Parietal Lobe
GroupValue95% CI
Part 2, AD and Amnestic MCI Elderly Participants7
Occipital Lobe
GroupValue95% CI
Part 2, AD and Amnestic MCI Elderly Participants9
Insula and Cingulate Cortex
GroupValue95% CI
Part 2, AD and Amnestic MCI Elderly Participants4
Hippocampus
GroupValue95% CI
Part 2, AD and Amnestic MCI Elderly Participants6
Amygdala
GroupValue95% CI
Part 2, AD and Amnestic MCI Elderly Participants5
Parahippocampal and Ambient Gyri
GroupValue95% CI
Part 2, AD and Amnestic MCI Elderly Participants6

Adverse events — posted to ClinicalTrials.gov

Time frame: Part 1: up to 5 weeks Part 2: up to 16 weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part 1, Healthy Young Participants
Serious: 0/3 (0%)
Deaths:
Part 2, Healthy Elderly Participants
Serious: 0/4 (0%)
Deaths:
Part 2, AD and Amnestic MCI Elderly Participants
Serious: 0/6 (0%)
Deaths:
Other adverse events (3 terms — click to expand)

ReactionSystemPart 1, Healthy Young Part…Part 2, Healthy Elderly Pa…Part 2, AD and Amnestic MC…
Vascular access site bruisingInjury, poisoning and procedural complications
Vascular access site hematomaInjury, poisoning and procedural complications
HeadacheNervous system disorders

Data from ClinicalTrials.gov NCT02562989 adverse events section.

Sponsor's own description

This 2-part, open-label study was designed to investigate the safety, tolerability, and efficacy of \[18F\]MK-6240, a Positron Emission Tomography (PET) imaging agent, for the quantification of neurofibrillary tangle (NFT) deposition in the brain. Brain NFT deposition is a pathologic finding in Alzheimer's Disease (AD), with brain NFT density shown to correlate with the severity of cognitive impairment in AD. The objectives of the study include performing the following with respect to \[18F\]MK-6240 administered as a PET imaging agent: 1) assess safety and tolerability; 2) determine radiation safety profile; 3) determine optimal imaging protocol parameters for quantification of brain NFTs in AD; 4) compare tracer binding in brain PET scans from participants with AD, participants with amnestic mild cognitive impairment (MCI) and healthy elderly participants; and 5) evaluate intra-subject test-retest (T-RT) variability of tracer uptake in brain regions of interest.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Tauvid™: The First FDA-Approved PET Tracer for Imaging Tau Pathology in Alzheimer's Disease.
    Jie CVML, Treyer V, Schibli R, Mu L. · · 2021 · cited 92× · PMID 33573211 · DOI 10.3390/ph14020110
  2. Drug Development in Alzheimer's Disease: The Contribution of PET and SPECT.
    Declercq LD, Vandenberghe R, Van Laere K, Verbruggen A, et al · · 2016 · cited 16× · PMID 27065872 · DOI 10.3389/fphar.2016.00088
  3. A dual-time-window protocol to reduce acquisition time of dynamic tau PET imaging using [<sup>18</sup>F]MK-6240.
    Kolinger GD, Vállez García D, Lohith TG, Hostetler ED, et al · · 2021 · cited 10× · PMID 34046730 · DOI 10.1186/s13550-021-00790-x

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