Trial Outcomes & Findings for [18F]MK-6240 Positron Emission Tomography (PET) Tracer First-in-Human Validation Study (MK-6240-001) (NCT NCT02562989)
NCT ID: NCT02562989
Last Updated: 2018-09-18
Results Overview
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.
COMPLETED
PHASE1
13 participants
Part 1: Up to 5 weeks; Part 2: up to 16 weeks
2018-09-18
Participant Flow
Participant milestones
| Measure |
Part 1, Healthy Young Participants
Healthy young participants received a single intravenous (IV) dose of \~185 megabecquerel (MBq) \[18F\]MK-6240 in Part 1 of the study.
|
Part 2, Healthy Elderly Participants
Healthy elderly participants received a single IV dose of \~160 MBq \[18F\]MK-6240, in Part 2 of the study.
|
Part 2, AD and Amnestic MCI Elderly Participants
AD and amnestic MCI participants received up to two IV doses of \~160 MBq \[18F\]MK-6240, in Part 2 of the study.
|
|---|---|---|---|
|
Overall Study
STARTED
|
3
|
4
|
6
|
|
Overall Study
COMPLETED
|
3
|
4
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
[18F]MK-6240 Positron Emission Tomography (PET) Tracer First-in-Human Validation Study (MK-6240-001)
Baseline characteristics by cohort
| Measure |
Part 1, Healthy Young Participants
n=3 Participants
Healthy young participants received a single intravenous (IV) dose of \~185 megabecquerel (MBq) \[18F\]MK-6240 in Part 1 of the study.
|
Part 2, Healthy Elderly Participants
n=4 Participants
Healthy elderly participants received a single IV dose of \~160 MBq \[18F\]MK-6240, in Part 2 of the study.
|
Part 2, AD and Amnestic MCI Elderly Participants
n=6 Participants
AD and amnestic MCI participants received up to two IV doses of \~160 MBq \[18F\]MK-6240, in Part 2 of the study.
|
Total
n=13 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
27.0 Years
STANDARD_DEVIATION 7.9 • n=5 Participants
|
65.3 Years
STANDARD_DEVIATION 5.4 • n=7 Participants
|
73.2 Years
STANDARD_DEVIATION 4.4 • n=5 Participants
|
60.1 Years
STANDARD_DEVIATION 19.9 • n=4 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Part 1: Up to 5 weeks; Part 2: up to 16 weeksPopulation: All participants as treated, consisting of all participants who received at least 1 dose of \[18F\]MK-6240
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.
Outcome measures
| Measure |
Part 1, Healthy Young Participants
n=3 Participants
Healthy young participants received a single intravenous (IV) dose of \~185 megabecquerel (MBq) \[18F\]MK-6240 in Part 1 of the study.
|
Part 2, Healthy Elderly Participants
n=4 Participants
Healthy elderly participants received a single IV dose of \~160 MBq \[18F\]MK-6240, in Part 2 of the study.
|
Part 2, AD and Amnestic MCI Elderly Participants
n=6 Participants
AD and amnestic MCI participants received up to two IV doses of \~160 MBq \[18F\]MK-6240, in Part 2 of the study.
|
|---|---|---|---|
|
Number of Participants With Adverse Events (AEs)
|
1 Participants
|
3 Participants
|
2 Participants
|
PRIMARY outcome
Timeframe: Part 1: Up to 5 weeks; Part 2: up to 16 weeksPopulation: All participants as treated, consisting of all participants who received at least 1 dose of \[18F\]MK-6240
The number of participants discontinuing study due to an AE was monitored.
Outcome measures
| Measure |
Part 1, Healthy Young Participants
n=3 Participants
Healthy young participants received a single intravenous (IV) dose of \~185 megabecquerel (MBq) \[18F\]MK-6240 in Part 1 of the study.
|
Part 2, Healthy Elderly Participants
n=4 Participants
Healthy elderly participants received a single IV dose of \~160 MBq \[18F\]MK-6240, in Part 2 of the study.
|
Part 2, AD and Amnestic MCI Elderly Participants
n=6 Participants
AD and amnestic MCI participants received up to two IV doses of \~160 MBq \[18F\]MK-6240, in Part 2 of the study.
|
|---|---|---|---|
|
Number of Participants Who Discontinued Study Due to an AE
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to approximately 5 hours following [18F]MK-6240 administrationPopulation: The analysis population included only healthy young participants enrolled in Part 1 of this study (N=3). As per study protocol, participants enrolled in Part 2 did not receive testing for effective dose of \[18F\]MK-6240 and, as a result, were not included in the analysis population.
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 then entered into a human biodistribution model to determine ED of \[18F\]MK-6240.
Outcome measures
| Measure |
Part 1, Healthy Young Participants
n=3 Participants
Healthy young participants received a single intravenous (IV) dose of \~185 megabecquerel (MBq) \[18F\]MK-6240 in Part 1 of the study.
|
Part 2, Healthy Elderly Participants
Healthy elderly participants received a single IV dose of \~160 MBq \[18F\]MK-6240, in Part 2 of the study.
|
Part 2, AD and Amnestic MCI Elderly Participants
AD and amnestic MCI participants received up to two IV doses of \~160 MBq \[18F\]MK-6240, in Part 2 of the study.
|
|---|---|---|---|
|
Effective Dose of [18F]MK-6240
|
29.4 µSv / MBq
Standard Deviation 0.6
|
—
|
—
|
PRIMARY outcome
Timeframe: Up to approximately 5 hours following [18F]MK-6240 administrationPopulation: The analysis population included only healthy young participants enrolled in Part 1 of this study (N=3). As per study protocol, participants enrolled in Part 2 did not receive testing for effective dose of \[18F\]MK-6240 and, as a result, were not included in the analysis population.
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.
Outcome measures
| Measure |
Part 1, Healthy Young Participants
n=3 Participants
Healthy young participants received a single intravenous (IV) dose of \~185 megabecquerel (MBq) \[18F\]MK-6240 in Part 1 of the study.
|
Part 2, Healthy Elderly Participants
Healthy elderly participants received a single IV dose of \~160 MBq \[18F\]MK-6240, in Part 2 of the study.
|
Part 2, AD and Amnestic MCI Elderly Participants
AD and amnestic MCI participants received up to two IV doses of \~160 MBq \[18F\]MK-6240, in Part 2 of the study.
|
|---|---|---|---|
|
Organ Effective Dose of [18F]MK-6240
Adrenals
|
12.7 µGy / MBq
Standard Deviation 1.0
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Brain
|
8.8 µGy / MBq
Standard Deviation 0.4
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Breasts
|
5.8 µGy / MBq
Standard Deviation 0.9
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Gallbladder Wall
|
202.0 µGy / MBq
Standard Deviation 111.0
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Lower Large Intestine Wall
|
46.4 µGy / MBq
Standard Deviation 5.5
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Small Intestine
|
116.0 µGy / MBq
Standard Deviation 13.3
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Stomach Wall
|
16.9 µGy / MBq
Standard Deviation 3.7
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Upper Large Intestine Wall
|
128.0 µGy / MBq
Standard Deviation 15.7
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Heart Wall
|
15.6 µGy / MBq
Standard Deviation 1.0
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Kidneys
|
33.5 µGy / MBq
Standard Deviation 4.8
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Liver
|
34.3 µGy / MBq
Standard Deviation 9.2
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Lungs
|
19.7 µGy / MBq
Standard Deviation 3.6
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Muscle
|
9.4 µGy / MBq
Standard Deviation 0.8
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Ovaries
|
28.3 µGy / MBq
Standard Deviation 2.0
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Pancreas
|
14.6 µGy / MBq
Standard Deviation 1.1
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Red Marrow
|
19.2 µGy / MBq
Standard Deviation 2.9
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Osteogenic Cells
|
16.9 µGy / MBq
Standard Deviation 1.5
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Skin
|
5.6 µGy / MBq
Standard Deviation 0.8
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Spleen
|
17.7 µGy / MBq
Standard Deviation 3.9
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Testes
|
3.0 µGy / MBq
Standard Deviation 5.1
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Thymus
|
6.9 µGy / MBq
Standard Deviation 1.1
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Thyroid
|
5.6 µGy / MBq
Standard Deviation 1.5
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Urinary Bladder Wall
|
128.0 µGy / MBq
Standard Deviation 31.8
|
—
|
—
|
|
Organ Effective Dose of [18F]MK-6240
Uterus
|
26.4 µGy / MBq
Standard Deviation 1.2
|
—
|
—
|
PRIMARY outcome
Timeframe: From 60 to 90 minutes following [18F]MK-6240 administrationPopulation: The analysis population included healthy elderly as well as AD/amnesic MCI participants enrolled in Part 2 of this study. As per study protocol, participants enrolled in Part 1 did not receive testing for SUVR (60-90 min) and, as a result, were not included in the analysis population.
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 minutes following \[18F\]MK-6240 administration to quantify tracer retention; referred to as "SUVR (60-90min)." An SUVR (60-90 min) \< 1 indicates decreased tracer retention at brain ROI relative to RR. An SUVR (60-90 min) = 1 indicates no difference in tracer retention at brain ROI relative to RR. An SUVR (60-90 min) \> 1 indicates increased tracer retention at brain ROI relative to RR.
Outcome measures
| Measure |
Part 1, Healthy Young Participants
Healthy young participants received a single intravenous (IV) dose of \~185 megabecquerel (MBq) \[18F\]MK-6240 in Part 1 of the study.
|
Part 2, Healthy Elderly Participants
n=4 Participants
Healthy elderly participants received a single IV dose of \~160 MBq \[18F\]MK-6240, in Part 2 of the study.
|
Part 2, AD and Amnestic MCI Elderly Participants
n=6 Participants
AD and amnestic MCI participants received up to two IV doses of \~160 MBq \[18F\]MK-6240, in Part 2 of the study.
|
|---|---|---|---|
|
Standardized Uptake Value Ratio (SUVR) of [18F]MK-6240 in Brain Regions of Interest
Frontal Lobe
|
—
|
0.95 SUVR (60-90 min)
Standard Deviation 0.07
|
1.22 SUVR (60-90 min)
Standard Deviation 0.47
|
|
Standardized Uptake Value Ratio (SUVR) of [18F]MK-6240 in Brain Regions of Interest
Temporal Lobe
|
—
|
0.98 SUVR (60-90 min)
Standard Deviation 0.07
|
1.64 SUVR (60-90 min)
Standard Deviation 0.72
|
|
Standardized Uptake Value Ratio (SUVR) of [18F]MK-6240 in Brain Regions of Interest
Parietal Lobe
|
—
|
0.95 SUVR (60-90 min)
Standard Deviation 0.06
|
1.42 SUVR (60-90 min)
Standard Deviation 0.80
|
|
Standardized Uptake Value Ratio (SUVR) of [18F]MK-6240 in Brain Regions of Interest
Occipital Lobe
|
—
|
1.01 SUVR (60-90 min)
Standard Deviation 0.06
|
1.61 SUVR (60-90 min)
Standard Deviation 0.92
|
|
Standardized Uptake Value Ratio (SUVR) of [18F]MK-6240 in Brain Regions of Interest
Insula and Cingulate Cortex
|
—
|
0.93 SUVR (60-90 min)
Standard Deviation 0.07
|
1.22 SUVR (60-90 min)
Standard Deviation 0.42
|
|
Standardized Uptake Value Ratio (SUVR) of [18F]MK-6240 in Brain Regions of Interest
Hippocampus
|
—
|
0.93 SUVR (60-90 min)
Standard Deviation 0.10
|
1.37 SUVR (60-90 min)
Standard Deviation 0.25
|
|
Standardized Uptake Value Ratio (SUVR) of [18F]MK-6240 in Brain Regions of Interest
Amygdala
|
—
|
0.84 SUVR (60-90 min)
Standard Deviation 0.11
|
1.67 SUVR (60-90 min)
Standard Deviation 0.40
|
|
Standardized Uptake Value Ratio (SUVR) of [18F]MK-6240 in Brain Regions of Interest
Parahippocampal and Ambient Gyri
|
—
|
0.96 SUVR (60-90 min)
Standard Deviation 0.11
|
1.71 SUVR (60-90 min)
Standard Deviation 0.39
|
|
Standardized Uptake Value Ratio (SUVR) of [18F]MK-6240 in Brain Regions of Interest
Fusiform Gyri
|
—
|
1.03 SUVR (60-90 min)
Standard Deviation 0.11
|
1.72 SUVR (60-90 min)
Standard Deviation 0.67
|
|
Standardized Uptake Value Ratio (SUVR) of [18F]MK-6240 in Brain Regions of Interest
Striatum
|
—
|
0.86 SUVR (60-90 min)
Standard Deviation 0.04
|
0.92 SUVR (60-90 min)
Standard Deviation 0.21
|
|
Standardized Uptake Value Ratio (SUVR) of [18F]MK-6240 in Brain Regions of Interest
Thalamus
|
—
|
0.85 SUVR (60-90 min)
Standard Deviation 0.06
|
0.81 SUVR (60-90 min)
Standard Deviation 0.13
|
|
Standardized Uptake Value Ratio (SUVR) of [18F]MK-6240 in Brain Regions of Interest
Substantia Nigra
|
—
|
1.10 SUVR (60-90 min)
Standard Deviation 0.11
|
1.08 SUVR (60-90 min)
Standard Deviation 0.14
|
|
Standardized Uptake Value Ratio (SUVR) of [18F]MK-6240 in Brain Regions of Interest
Brainstem
|
—
|
0.78 SUVR (60-90 min)
Standard Deviation 0.09
|
0.76 SUVR (60-90 min)
Standard Deviation 0.09
|
PRIMARY outcome
Timeframe: Up to 16 weeks following initial dose of [18F]MK-6240Population: Includes only elderly AD/MCI participants (Part 2); per protocol, young (Part 1) and elderly (Part 2) healthy participants did not receive retest scan. Of the 6 AD/MCI participants, only 2 received T-RT scans. In one participant, motion artifacts prevented T-RT analysis. For the one participant included, T-RT scans were separated by 16 weeks.
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.
Outcome measures
| Measure |
Part 1, Healthy Young Participants
Healthy young participants received a single intravenous (IV) dose of \~185 megabecquerel (MBq) \[18F\]MK-6240 in Part 1 of the study.
|
Part 2, Healthy Elderly Participants
Healthy elderly participants received a single IV dose of \~160 MBq \[18F\]MK-6240, in Part 2 of the study.
|
Part 2, AD and Amnestic MCI Elderly Participants
n=1 Participants
AD and amnestic MCI participants received up to two IV doses of \~160 MBq \[18F\]MK-6240, in Part 2 of the study.
|
|---|---|---|---|
|
Intra-subject Test-Retest (T-RT) Variability of Standardized Uptake Value Ratio (SUVR) in Brain Regions of Interest
Frontal Lobe
|
—
|
—
|
7 Percent
|
|
Intra-subject Test-Retest (T-RT) Variability of Standardized Uptake Value Ratio (SUVR) in Brain Regions of Interest
Temporal Lobe
|
—
|
—
|
12 Percent
|
|
Intra-subject Test-Retest (T-RT) Variability of Standardized Uptake Value Ratio (SUVR) in Brain Regions of Interest
Parietal Lobe
|
—
|
—
|
7 Percent
|
|
Intra-subject Test-Retest (T-RT) Variability of Standardized Uptake Value Ratio (SUVR) in Brain Regions of Interest
Occipital Lobe
|
—
|
—
|
9 Percent
|
|
Intra-subject Test-Retest (T-RT) Variability of Standardized Uptake Value Ratio (SUVR) in Brain Regions of Interest
Insula and Cingulate Cortex
|
—
|
—
|
4 Percent
|
|
Intra-subject Test-Retest (T-RT) Variability of Standardized Uptake Value Ratio (SUVR) in Brain Regions of Interest
Hippocampus
|
—
|
—
|
6 Percent
|
|
Intra-subject Test-Retest (T-RT) Variability of Standardized Uptake Value Ratio (SUVR) in Brain Regions of Interest
Amygdala
|
—
|
—
|
5 Percent
|
|
Intra-subject Test-Retest (T-RT) Variability of Standardized Uptake Value Ratio (SUVR) in Brain Regions of Interest
Parahippocampal and Ambient Gyri
|
—
|
—
|
6 Percent
|
|
Intra-subject Test-Retest (T-RT) Variability of Standardized Uptake Value Ratio (SUVR) in Brain Regions of Interest
Fusiform Gyri
|
—
|
—
|
17 Percent
|
|
Intra-subject Test-Retest (T-RT) Variability of Standardized Uptake Value Ratio (SUVR) in Brain Regions of Interest
Striatum
|
—
|
—
|
4 Percent
|
|
Intra-subject Test-Retest (T-RT) Variability of Standardized Uptake Value Ratio (SUVR) in Brain Regions of Interest
Thalamus
|
—
|
—
|
2 Percent
|
|
Intra-subject Test-Retest (T-RT) Variability of Standardized Uptake Value Ratio (SUVR) in Brain Regions of Interest
Substantia Nigra
|
—
|
—
|
6 Percent
|
|
Intra-subject Test-Retest (T-RT) Variability of Standardized Uptake Value Ratio (SUVR) in Brain Regions of Interest
Brainstem
|
—
|
—
|
2 Percent
|
Adverse Events
Part 1, Healthy Young Participants
Part 2, Healthy Elderly Participants
Part 2, AD and Amnestic MCI Elderly Participants
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Part 1, Healthy Young Participants
n=3 participants at risk
Healthy young participants received a single intravenous (IV) dose of \~185 megabecquerel (MBq) \[18F\]MK-6240 in Part 1 of the study.
|
Part 2, Healthy Elderly Participants
n=4 participants at risk
Healthy elderly participants received a single IV dose of \~160 MBq \[18F\]MK-6240, in Part 2 of the study.
|
Part 2, AD and Amnestic MCI Elderly Participants
n=6 participants at risk
AD and amnestic MCI participants received up to two IV doses of \~160 MBq \[18F\]MK-6240, in Part 2 of the study.
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Vascular access site bruising
|
0.00%
0/3 • Part 1: up to 5 weeks Part 2: up to 16 weeks
|
50.0%
2/4 • Number of events 2 • Part 1: up to 5 weeks Part 2: up to 16 weeks
|
0.00%
0/6 • Part 1: up to 5 weeks Part 2: up to 16 weeks
|
|
Injury, poisoning and procedural complications
Vascular access site hematoma
|
0.00%
0/3 • Part 1: up to 5 weeks Part 2: up to 16 weeks
|
25.0%
1/4 • Number of events 1 • Part 1: up to 5 weeks Part 2: up to 16 weeks
|
33.3%
2/6 • Number of events 2 • Part 1: up to 5 weeks Part 2: up to 16 weeks
|
|
Nervous system disorders
Headache
|
33.3%
1/3 • Number of events 1 • Part 1: up to 5 weeks Part 2: up to 16 weeks
|
0.00%
0/4 • Part 1: up to 5 weeks Part 2: up to 16 weeks
|
0.00%
0/6 • Part 1: up to 5 weeks Part 2: up to 16 weeks
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Results disclosure agreements
- Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
- Publication restrictions are in place
Restriction type: OTHER