Alzheimer's DiseasePhase 1NCT01385033
[18F]MK-3328 as a Possible Novel Positron Emission Tomography (PET) Tracer for the Detection of Brain Amyloid Plaques (MK-3328-002)
A Phase 1 study testing [18F]MK-3328 in people with Alzheimer's Disease, run by Merck Sharp & Dohme LLC.
Trial summary
The purpose of this study is to evaluate radiolabeled [18F]MK-3328 as a PET tracer for estimating the regional distribution and extent of amyloid plaques in participants suffering from amnestic mild cognitive impairment (aMCI) and Alzheimer's Disease (AD) versus healthy young and elderly participants. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- [18F]MK-3328
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- 19 Aug 2011to 15 May 2012
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- All participants:
- Body Mass Index (BMI) between 18 and 35, inclusive, at the pre-screening visit
- Electrocardiogram (ECG) measurements must be clinically acceptable
- Must consent to apolipoprotein E4 (ApoE4) genotyping
- Healthy young (HY) and healthy elderly (HE) participants:
- Male or female between the ages of 18 and 45 years (HY) and 65 to 85 years (HE) at pre-screening visit
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- Judged to be in good health
- Considered generally cognitively normal
- Participants with aMCI or AD:
- Male or female between the ages of 50 and 85 years (aMCI) and 65 to 85 years (AD) at pre-screening visit
- Is in stable medical condition, with existing medical conditions stable for 3 months prior to the pre-screening visit
- Free of any clinically significant disease that would interfere with the study and radiographic evaluations
- Specific cognitive testing requirements for participants aMCI: a history of subjective memory decline with gradual onset and slow progression ≥1 year before Screening, corroborated by an informant; objective impairment in verbal memory as defined by >1 SD below the age adjusted mean for items remembered on the Delayed Word Recall Task of the Alzheimer's Disease Assessment Scale (ADAS) Cog12 at Screening; a global Clinical Dementia Rating (CDR) score of 0.5 and a memory box score of 0.5 or greater at Screening; and an Mini Mental Status Examination (MMSE) score ≥ 24 at Pre-Screening
- Specific cognitive testing requirements for participants with mild-to-moderate AD: MMSE score between 16 and 23, inclusive, at Pre-Screening; modified Hachinski score ≤4 at Screening; meets National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD at Screening; Clinical Dementia Rating (CDR) Scale = 0.5, 1 or 2 at Screening; screening magnetic resonance imaging (MRI) scan consistent with a diagnosis of AD
- Participants with AD must have reliable informant/caregiver who is able to accompany the participant to all clinic visits, is able to provide information to study investigator/staff via telephone contact, and agrees to return for per-protocol follow-up visits and procedures
- Participant or participant's legal representative (for participants with AD if the investigator determines that the participant is unable to provide his/her own informed consent) understands the study procedures, and gives written informed consent. For AD participants, the participant's caregiver must also give written informed consent
- Agrees not to participate in any other investigational study that precludes participating in this study
Who cannot join
- Mentally or legally incapacitated, significant emotional problems at the time of pre-screening visit or expected during the conduct of the study, or has a history of a clinically significant psychiatric disorder over the last 2 years
- Medical history of psychiatric or personality disorders that in the opinion of the investigator and sponsor, affects the ability to participate in the trial
- Has received anti-amyloid agents (e.g., tarenflurbil, tramiprosate) in the 3 months period before screening and has received anti-amyloid antibodies (e.g., bapineuzumab) or anti-amyloid vaccine
- Has participated in MK-3328 PN001 trial
- Has a history of any illness that, in the opinion of the study investigator, might confound the results of the study or poses an additional risk by their participation in the study
- Has had any surgical or medical condition that might significantly alter the distribution, metabolism, or excretion of [18F]-PET tracer
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- Has incidental findings on an MRI scan that is pathognomonic for an active disease or pathological process that requires medical intervention
- Has a history of significant infection within 4 weeks prior to study drug administration that in the opinion of the investigator, affects the ability to participate in the trial
- Has an estimated creatinine clearance of ≤30 mL/min based on the Cockcroft-Gault equation
- Has a history of stroke, chronic seizures, or major neurological disorder
- Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or other diseases that in the opinion of the investigator would prevent them from safely participating in the study
- Has a history of neoplastic disease, except: adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix; other malignancies that have been successfully treated prior to the Pre-Screening visit and appropriate follow-up has revealed no evidence of recurrence; or are highly unlikely to sustain a recurrence for the duration of the study
- Is pregnant, intending to become pregnant within 3 months of ending the study, or is nursing
- Consumes excessive amounts of alcohol, or coffee, tea, cola, or other caffeinated beverages
- Has had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pre-screening visit
- Has a history of significant multiple and/or severe allergies (including latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
- Is currently a regular user of any illicit drugs or has a positive screen for drugs with high potential for abuse during the screening period or has a history of drug (including alcohol) abuse within approximately 2 years
- Has a contraindication to undergo PET or MRI including but not limited to claustrophobia, excessive weight or girth, presence of a pacemaker, aneurysm clips, artificial heart valve, ear implant, or metal fragments/foreign objects in the eyes, skin or body
- Has been exposed to ionizing radiation >10 millisievert (mSv) in other research studies within the last 12 months
- Has any disease or condition, or takes any medication that could: interfere with the assessments of safety, tolerability, or biokinetics of the tracer; pose unnecessary risk to the participant; or cause undue discomfort
About this study
Official title: A Clinical Trial to Characterize the Performance of [18F]MK-3328 in Subjects With Alzheimer's Disease or Mild Cognitive Impairment, and Healthy Young, and Healthy Elderly Subjects
The purpose of this study is to evaluate radiolabeled [18F]MK-3328 as a PET tracer for estimating the regional distribution and extent of amyloid plaques in participants suffering from amnestic mild cognitive impairment (aMCI) and Alzheimer's Disease (AD) versus healthy young and elderly participants. The study hypotheses will test whether [18F]MK-3328 can discriminate between AD participants and cognitively normal elderly control participants as measured by brain regional tracer uptake.
- Conditions
- Alzheimer's Disease
- Being tested
- [18F]MK-3328
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[18F]MK-3328Drug
IV dose of ~150 megabecquerel (MBq) [18F]MK-3328
| Study group | Role | What they receive |
|---|---|---|
| Part I, Healthy Elderly (HE) and AD Participants | Experimental | HE and AD participants will receive a single intravenous (IV) dose of ~150 megabecquerel (MBq) [18F]MK-3328 in Part I of the study Receives: Drug: [18F]MK-3328 |
| Part II, Healthy Young, HE and AD Participants | Experimental | Healthy Young, HE and AD participants will receive a single IV dose of ~150 megabecquerel (MBq) [18F]MK-3328 in Part II of the study Receives: Drug: [18F]MK-3328 |
| Part III, Participants with aMCI | Experimental | Participants with aMCI will receive a single IV dose of ~150 megabecquerel (MBq) [18F]MK-3328 in Part III of the study Receives: Drug: [18F]MK-3328 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Receiver Operating Curve (AUC of ROC) for Distinguishing Between AD and HE Participants Based on Brain Cortical [18F]MK-3328 Standard Uptake Value Ratio (SUVR)
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.
Measured: 60-90 minutes post dose
Brain Cortical [18F]MK-3328 SUVR in AD Participants and HE Participants
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).
Measured: 60-90 minutes post dose
Amyloid Plaque Burden Threshold Determined by the Trimmed HE Sample Mean and SD Brain Cortical [18F]MK-3328 SUVR
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.
Measured: 60-90 minutes post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2011 (estimated)
- Study start19 Aug 2011
- Primary completion15 May 2012
- Study completion15 May 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01385033
- Sponsor's protocol ID
- 3328-002
- Status last verified
- Oct 2018
- First submitted
- 8 Jun 2011
- Last updated
- 8 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Trial to Characterize the Performance of [18F]MK-3328 in Subjects With Alzheimer's Disease or Mild Cognitive Impairment, and Healthy Young, and Healthy Elderly Subjects
- ClinicalTrials.gov ID
- NCT01385033
- Acronym / sponsor ID
- 3328-002
- Conditions
- Alzheimer's Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 19 Aug 2011 (actual)
- Primary completion
- 15 May 2012 (actual)
- Study completion
- 15 May 2012 (actual)
- First posted
- 29 Jun 2011 (estimated)
- Results
- Posted 20 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate radiolabeled [18F]MK-3328 as a PET tracer for estimating the regional distribution and extent of amyloid plaques in participants suffering from amnestic mild cognitive impairment (aMCI) and Alzheimer's Disease (AD) versus healthy young and elderly participants. The study hypotheses will test whether [18F]MK-3328 can discriminate between AD participants and cognitively normal elderly control participants as measured by brain regional tracer uptake.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part I, Healthy Elderly (HE) and AD Participants | Experimental | Drug: [18F]MK-3328HE and AD participants will receive a single intravenous (IV) dose of ~150 megabecquerel (MBq) [18F]MK-3328 in Part I of the study |
| Part II, Healthy Young, HE and AD Participants | Experimental | Drug: [18F]MK-3328Healthy Young, HE and AD participants will receive a single IV dose of ~150 megabecquerel (MBq) [18F]MK-3328 in Part II of the study |
| Part III, Participants with aMCI | Experimental | Drug: [18F]MK-3328Participants with aMCI will receive a single IV dose of ~150 megabecquerel (MBq) [18F]MK-3328 in Part III of the study |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Body Mass Index (BMI) between 18 and 35, inclusive, at the pre-screening visit
- Electrocardiogram (ECG) measurements must be clinically acceptable
- Must consent to apolipoprotein E4 (ApoE4) genotyping
- Male or female between the ages of 18 and 45 years (HY) and 65 to 85 years (HE) at pre-screening visit
- Judged to be in good health
Key exclusion criteria (20 listed)
- Mentally or legally incapacitated, significant emotional problems at the time of pre-screening visit or expected during the conduct of the study, or has a history of a clinically significant psychiatric disorder over the last 2 years
- Medical history of psychiatric or personality disorders that in the opinion of the investigator and sponsor, affects the ability to participate in the trial
- Has received anti-amyloid agents (e.g., tarenflurbil, tramiprosate) in the 3 months period before screening and has received anti-amyloid antibodies (e.g., bapineuzumab) or anti-amyloid vaccine
- Has participated in MK-3328 PN001 trial
- Has a history of any illness that, in the opinion of the study investigator, might confound the results of the study or poses an additional risk by their participation in the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [18F]MK-3328IV dose of ~150 megabecquerel (MBq) [18F]MK-3328 | Drug | Part I, Healthy Elderly (HE) and AD Participants, Part II, Healthy Young, HE and AD Participants, Part III, Participants with aMCI |
Primary outcome
Area Under the Receiver Operating Curve (AUC of ROC) for Distinguishing Between AD and HE Participants Based on Brain Cortical [18F]MK-3328 Standard Uptake Value Ratio (SUVR)
Time frame: 60-90 minutes post dose
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.
Brain Cortical [18F]MK-3328 SUVR in AD Participants and HE Participants
Time frame: 60-90 minutes post dose
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).
Amyloid Plaque Burden Threshold Determined by the Trimmed HE Sample Mean and SD Brain Cortical [18F]MK-3328 SUVR
Time frame: 60-90 minutes post dose
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing [18F]MK-3328 in people with Alzheimer's Disease, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Receiver Operating Curve (AUC of ROC) for Distinguishing Between AD and HE Participants Based on Brain Cortical [18F]MK-3328 Standard Uptake Value Ratio (SUVR) (time frame: 60-90 minutes post dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2018.