Trial Outcomes & Findings for [18F]MK-3328 as a Possible Novel Positron Emission Tomography (PET) Tracer for the Detection of Brain Amyloid Plaques (MK-3328-002) (NCT NCT01385033)

Last Updated: 2018-11-08

Results Overview

Using PET brain images acquired after dosing, regions of interest (ROIs) are drawn in identified brain areas. The ROIs are projected onto all frames of the dynamic PET scans in order to generate \[18F\]MK-3328 tissue time-activity curves (TACs). SUVR is calculated as the ratio of the average \[18F\]MK-3328 uptake over 60-90 minutes post dose in the target brain region and the cerebellum. Cortical SUVR is determined, which is a mean SUVR derived from SUVR from multiple brain regions (frontal cortex, parietal cortex, anterior cingulate gyrus, posterior cingulate gyrus, temporal cortex, lateral temporal cortex and occipital cortices). The receiver operating curve (ROC) for determining whether a participant is in HE or AD group by using cortical SUVR values is determined. The ROC is a plot of sensitivity on the y-axis versus 1-specificity (false positive rate) on the x-axis for the range of cortical SUVR threshold values. The AUC of ROC is determined.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

20 participants

Primary outcome timeframe

60-90 minutes post dose

Results posted on

2018-11-08

Participant Flow

Part II and III were not conducted due to early termination of the study

Participant milestones

Participant milestones
Measure	Alzheimer's Disease (AD) Participants (Part I) AD participants received a single intravenous (IV) dose of \~150 megabecquerel (MBq) \[18F\]MK-3328, followed by positron emission tomography (PET) imaging of the brain (Part I)	Healthy Elderly (HE) Participants (Part I) HE participants received a single IV dose of \~150 MBq \[18F\]MK-3328, followed by PET imaging of the brain (Part I)
Part I STARTED	6	14
Part I COMPLETED	6	14
Part I NOT COMPLETED	0	0
Part II STARTED	0	0
Part II COMPLETED	0	0
Part II NOT COMPLETED	0	0
Part III STARTED	0	0
Part III COMPLETED	0	0
Part III NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

[18F]MK-3328 as a Possible Novel Positron Emission Tomography (PET) Tracer for the Detection of Brain Amyloid Plaques (MK-3328-002)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AD Participants n=6 Participants AD participants received a single IV dose of \~150 MBq \[18F\]MK-3328, followed by PET imaging of the brain	HE Participants n=14 Participants HE participants received a single IV dose of \~150 MBq \[18F\]MK-3328, followed by PET imaging of the brain	Total n=20 Participants Total of all reporting groups
Age, Continuous	63.8 years STANDARD_DEVIATION 5.8 • n=5 Participants	71.9 years STANDARD_DEVIATION 5.8 • n=7 Participants	69.5 years STANDARD_DEVIATION 6.8 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: 60-90 minutes post dose

Population: The study was terminated early before completion of Part I. Given the low number of enrolled AD participants (6 of up to 15 planned in Part I), the interim analysis for futility in Part I was not conducted and the potential of \[18F\]MK-3328 to distinguish between AD and HE participants was not assessed.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 60-90 minutes post dose

Population: The study was terminated early before completion of Part I. Given the low number of enrolled AD participants (6 of up to 15 planned in Part I), the interim analysis for futility in Part I was not conducted and the determination of brain cortical \[18F\]MK-3328 SUVR values in AD and HE participants was not performed.

Using PET brain images acquired after dosing, ROIs are drawn in identified brain areas. The ROIs are projected onto all frames of the dynamic PET scans in order to generate \[18F\]MK-3328 tissue TACs. SUVR is calculated as the ratio of the average \[18F\]MK-3328 uptake over 60-90 minutes post dose in the target brain region and the cerebellum. Cortical SUVR is reported, which is a mean SUVR derived from SUVR from multiple brain regions (frontal cortex, parietal cortex, anterior cingulated gyrus, posterior cingulated gyrus, temporal cortex, lateral temporal cortex and occipital cortices). A trimming procedure will be applied to remove the sub-population of HE participants who have positive amyloid plaque burden. The 1st and 2nd quartiles of the cortical SUVR distribution, Q1 and Q2, are computed for HE data; values with SUVR ≥(Q2-Q1)\*3 are removed before calculation of HE mean (trimmed) and standard deviation (SD)(trimmed).

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 60-90 minutes post dose

Population: The study was terminated early before completion of Part I. Given the low number of enrolled AD participants (6 of up to 15 planned in Part I), the interim analysis for futility in Part I was not conducted and the determination of an amyloid plaque burden threshold using PET imaging data obtained after \[18F\]MK-3328 administration was not performed.

Using PET brain images acquired after dosing, ROIs are drawn in identified brain areas. ROIs are projected onto all frames of the dynamic PET scans in order to generate \[18F\]MK-3328 tissue TACs. SUVR is calculated as the ratio of the average \[18F\]MK-3328 uptake over 60-90 minutes post dose in the target brain region and the cerebellum. Cortical SUVR is determined, which is a mean SUVR derived from SUVR from multiple brain regions. The 1st and 2nd quartiles of the cortical SUVR distribution, Q1 and Q2, are computed for HE data; values with SUVR ≥(Q2-Q1)\*3 are removed before calculation of HE mean (trimmed) and SD (trimmed). This step is performed to remove HE participants with positive plaque burden. Using HE data, the threshold for classification of plaque burden as positive/negative will be calculated as mean (trimmed) + k\*SD (trimmed). Value of k will be chosen to fine tune sensitivity/specificity, with specificity of at least 0.9 in the sub-group remaining after trimming of data.

Outcome measures

Outcome data not reported

Adverse Events

All Study Participants

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	All Study Participants n=20 participants at risk Participants received a single IV dose of \~150 MBq \[18F\]MK-3328, followed by PET imaging of the brain
Gastrointestinal disorders Diarrhoea	5.0% 1/20 • Up to 14 days after last dose
General disorders Injection site pain	5.0% 1/20 • Up to 14 days after last dose
Infections and infestations Sinusitis	5.0% 1/20 • Up to 14 days after last dose
Nervous system disorders Presyncope	5.0% 1/20 • Up to 14 days after last dose

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Email: [email protected]

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 study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER