Analysis of 18F-AV-1451 PET Imaging in Cognitively Healthy, MCI, and AD Subjects (MCI)
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| ClinicalTrials.gov Identifier: NCT02016560 |
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Recruitment Status :
Completed
First Posted : December 20, 2013
Results First Posted : August 24, 2020
Last Update Posted : September 22, 2020
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Sponsor:
Avid Radiopharmaceuticals
Information provided by (Responsible Party):
Avid Radiopharmaceuticals
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Brief Summary:
A Phase 2/3 cross-sectional and longitudinal observational study evaluating imaging characteristics of flortaucipir in control subjects and patients with clinically defined MCI and AD dementia (AD).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Alzheimer's Disease | Drug: florbetapir F 18 Drug: Flortaucipir F18 Procedure: Brain PET Scan | Phase 2 Phase 3 |
This study was conducted in 2 phases: a Phase 2 Exploratory Phase and a Phase 3 Confirmatory Phase. An overarching goal of the Exploratory Phase of this protocol was to further investigate the pattern of flortaucipir PET imaging across the disease course, in cognitively healthy subjects through patients with cognitive decline. To accomplish this goal, the protocol investigated flortaucipir results in younger and older cognitively healthy normal volunteers and patients with clinical diagnoses for cognitive complaints, ranging from MCI to mild and moderate AD dementia. Additionally, the Exploratory Phase of this protocol investigated relationships between flortaucipir PET signal and cognitive decline over the 18-month study period.
The second, Confirmatory Phase of the study was designed to provide independent validation of the relationships observed in the exploratory analyses of the first phase. In particular, the goal of the second phase was to confirm the relationship between flortaucipir uptake in the brain as measured by PET signals at baseline and the subsequent rate of cognitive decline observed over the 18-month longitudinal follow up.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 383 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Intervention Model Description: | All subjects in both the exploratory and confirmatory phases of the study, receive both florbetapir and florbetapir scans, regardless of subgroup assignment. |
| Masking: | Single (Outcomes Assessor) |
| Masking Description: | Applies only to confirmatory phase: the independent readers are blinded to all clinical information. |
| Primary Purpose: | Diagnostic |
| Official Title: | An Open Label, Multicenter Study, Evaluating the Safety and Imaging Characteristics of 18F-AV-1451 in Cognitively Healthy Volunteers, Subjects With Mild Cognitive Impairment, and Subjects With Alzheimer's Disease |
| Actual Study Start Date : | December 2013 |
| Actual Primary Completion Date : | July 28, 2017 |
| Actual Study Completion Date : | July 28, 2017 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Alzheimer disease
Drug Information available for:
Florbetapir F-18
| Arm | Intervention/treatment |
|---|---|
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Experimental: Exploratory Cognitively Healthy Subjects
Subjects will receive an IV injection, 370 megabecquerel (MBq) (10 millicurie [mCi]), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline.
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Drug: florbetapir F 18
Other Names:
Drug: Flortaucipir F18 Other Names:
Procedure: Brain PET Scan positron emission tomography (PET) scan of the brain |
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Experimental: Exploratory MCI Subjects
Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline, 9 months and 18 months.
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Drug: florbetapir F 18
Other Names:
Drug: Flortaucipir F18 Other Names:
Procedure: Brain PET Scan positron emission tomography (PET) scan of the brain |
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Experimental: Exploratory AD Subjects
Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline, 9 months and 18 months.
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Drug: florbetapir F 18
Other Names:
Drug: Flortaucipir F18 Other Names:
Procedure: Brain PET Scan positron emission tomography (PET) scan of the brain |
|
Experimental: Confirmatory Subjects
Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 and flortaucipir at baseline.
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Drug: florbetapir F 18
Other Names:
Drug: Flortaucipir F18 Other Names:
Procedure: Brain PET Scan positron emission tomography (PET) scan of the brain |
Primary Outcome Measures :
- Confirmatory Phase: Relationship Between Neocortical Flortaucipir Uptake and the Subsequent Rate of Cognitive Decline [ Time Frame: between baseline and 18 months ]Confirm the relationship between neocortical flortaucipir uptake and the subsequent rate of cognitive decline at longitudinal follow up that was observed in the Exploratory Phase of the study. Patients were assigned to groups by majority classification of the flortaucipir positron emission tomography (PET) scan by five independent imaging physicians. Clinically meaningful cognitive and functional deterioration was defined as a 1 point or greater worsening on clinical dementia rating - sum of boxes (CDR-SB) score over the follow-up period.
- Exploratory Phase: Cross-sectional Flortaucipir Imaging Results [ Time Frame: baseline scan ]Flortaucipir standardized uptake value ratio (SUVr). A value of 1 signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain.
- Exploratory Phase: Longitudinal Change in Tau Deposition Over Time, by Amyloid Status [ Time Frame: baseline and 18 months ]Assess the rate of change of tau deposition as measured by flortaucipir uptake (SUVr) over time. Change = 18 months SUVr - baseline SUVr.
Secondary Outcome Measures :
- Confirmatory Phase: Diagnostic Performance of Flortaucipir Visual Read [ Time Frame: baseline and 18 months ]This analysis used dichotomized CDR-SB change as a truth standard (1 point or more worsening = true positive vs. less than 1 point worsening = true negative) to assess the diagnostic performance of baseline Advanced AD tau status (τAD++) as determined by flortaucipir scan interpretation. Sensitivity and Specificity were calculated for each of the 5 independent imaging readers. Sensitivity is the percentage of true positive cases correctly identified by an Advanced AD pattern scan. Specificity is the percentage of true negative cases correctly identified by scans that were not classified as Advanced AD pattern.
- Exploratory Phase: Correlation Between Flortaucipir SUVr and Age [ Time Frame: baseline scan ]Flortaucipir standardized uptake value ratio (SUVr). A value of 1 signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 20 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
Criteria
Inclusion Criteria:
Exploratory Cognitively Healthy Subjects
- ≥ 20 to ≤ 40 years of age OR ≥ 50 years of age
- Mini-mental state examination (MMSE) ≥ 29
- No significant history of cognitive impairment
Exploratory MCI Subjects
- ≥ 50 years of age
- MMSE ≥ 24
- Have MCI consistent with National Institute on Aging-Alzheimer's Association (NIA-AA) working group's diagnostic guidelines for AD
- Have a study partner that can report on subject's activities of daily living
Exploratory AD Subjects
- ≥ 50 years of age
- MMSE > 10
- Have possible or probable AD based on the NIA-AA working group's diagnostic guidelines for AD
- Have a study partner that can report on subject's activities of daily living
Confirmatory Subjects
- ≥ 50 years of age
- MMSE ≥ 20 and ≤ 27
- Cognitively impaired subjects with either MCI or dementia with a suspected neurodegenerative cause
- Have a study partner that can report on subject's activities of daily living
Exclusion Criteria:
- Current clinically significant psychiatric disease
- Evidence of structural brain abnormalities
- History of moderate or severe traumatic brain injury
- Current clinically significant cardiovascular disease or ECG abnormalities, or additional risk factors for Torsades de Pointes
- Current clinically significant infectious disease, endocrine or metabolic disease, pulmonary, renal or hepatic impairment, or cancer
- History of alcohol or substance abuse or dependence
- Females of childbearing potential who are not surgically sterile, not refraining from sexual activity or not using reliable methods of contraception
- Have received or participated in a trial with investigational medications in the past 30 days
- Have had a non-study related radiopharmaceutical imaging or treatment procedure within 7 days prior to the study imaging session.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02016560
Locations
Show 27 study locations
Sponsors and Collaborators
Avid Radiopharmaceuticals
Study Documents (Full-Text)
Documents provided by Avid Radiopharmaceuticals:
Documents provided by Avid Radiopharmaceuticals:
Study Protocol [PDF] August 7, 2015
Statistical Analysis Plan: Confirmatory Phase SAP [PDF] January 5, 2018
Statistical Analysis Plan: Confirmatory Phase Addendum SAP [PDF] January 5, 2018
Statistical Analysis Plan: Exploratory Phase SAP [PDF] November 27, 2017
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Avid Radiopharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT02016560 |
| Other Study ID Numbers: |
18F-AV-1451-A05 |
| First Posted: | December 20, 2013 Key Record Dates |
| Results First Posted: | August 24, 2020 |
| Last Update Posted: | September 22, 2020 |
| Last Verified: | September 2020 |
Additional relevant MeSH terms:
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Alzheimer Disease Dementia Brain Diseases Central Nervous System Diseases Nervous System Diseases |
Tauopathies Neurodegenerative Diseases Neurocognitive Disorders Mental Disorders |