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Alzheimer's DiseasePhase 2/3MCINCT02016560

Analysis of 18F-AV-1451 PET Imaging in Cognitively Healthy, MCI, and AD Subjects

A Phase 2/3 study testing florbetapir F 18, Flortaucipir F18 and Brain PET Scan in people with Alzheimer's Disease, run by Avid Radiopharmaceuticals at 27 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 20 years and olderHealthy volunteers can take part
Conditions the study is for
Alzheimer's Disease
What is being tested?
florbetapir F 18, Flortaucipir F18 and Brain PET Scan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
383 participants
Where
27 sitesUnited States
Study dates
Dec 2013to 28 Jul 2017
Phase
Phase 2/3
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 20 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
Show all 19Show fewer
  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • 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.

Trial locations and contacts

27 sites in 1 country.

27 sites in 1 country

United States27 sites
  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Boston University

    Boston, Massachusetts, 02118

  • Quantum Laboratories

    Deerfield Beach, Florida, 33064

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • 21st Century Oncology

    Fort Myers, Florida, 33912

  • UC Irvine

    Irvine, California, 92697

  • Las Vegas Radiology

    Las Vegas, Nevada, 89147

  • Molecular NeuroImaging

    New Haven, Connecticut, 06510

  • Center for Brain Health - NYU Langone Medical Center

    New York, New York, 10016

  • Hoag Memorial

    Newport Beach, California, 92663

  • Sandlake Imaging

    Orlando, Florida, 32806

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Banner Alzheimer's Institute

    Phoenix, Arizona, 85006

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Butler Hospital

    Providence, Rhode Island, 02906

  • Alzheimer's Disease Center

    Quincy, Massachusetts, 02169

  • Norther California PET Imaging Center

    Sacramento, California, 95816

  • UC Davis

    Sacramento, California, 95817

  • UC San Francisco

    San Francisco, California, 94158

  • Neurological Research Institute

    Santa Monica, California, 90404

  • Four Peaks Neurology

    Scottsdale, Arizona, 85258

  • Mayo Clinic

    Scottsdale, Arizona, 85259

  • Center for Clinical Imaging Research

    St Louis, Missouri, 63110

  • Meridien Research

    St. Petersburg, Florida, 33709

  • Banner Sun Health Research Institute

    Sun City, Arizona, 85351

  • USF Health Byrd Alzheimer's Center

    Tampa, Florida, 33613

  • Independent Imaging

    West Palm Beach, Florida, 33407

Other trials in United States

About this study

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

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).

Read the detailed description

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.

Being tested
florbetapir F 18, Flortaucipir F18, Brain PET Scan
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • florbetapir F 18Drug

    Also called Amyvid, 18F-AV-45

  • Flortaucipir F18Drug

    Also called T807, 18F-AV-1451

  • Brain PET ScanProcedure or surgery

    positron emission tomography (PET) scan of the brain

Study groups in NCT02016560
Study groupRoleWhat they receive
Exploratory Cognitively Healthy SubjectsExperimentalSubjects 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.
Receives: Drug: florbetapir F 18; Drug: Flortaucipir F18; Procedure: Brain PET Scan
Exploratory MCI SubjectsExperimentalSubjects 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.
Receives: Drug: florbetapir F 18; Drug: Flortaucipir F18; Procedure: Brain PET Scan
Exploratory AD SubjectsExperimentalSubjects 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.
Receives: Drug: florbetapir F 18; Drug: Flortaucipir F18; Procedure: Brain PET Scan
Confirmatory SubjectsExperimentalSubjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 and flortaucipir at baseline.
Receives: Drug: florbetapir F 18; Drug: Flortaucipir F18; Procedure: Brain PET Scan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Confirmatory Phase: Relationship Between Neocortical Flortaucipir Uptake and the Subsequent Rate of Cognitive Decline

    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.

    Measured: between baseline and 18 months

  2. Exploratory Phase: Cross-sectional Flortaucipir Imaging Results

    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.

    Measured: baseline scan

  3. Exploratory Phase: Longitudinal Change in Tau Deposition Over Time, by Amyloid Status

    Assess the rate of change of tau deposition as measured by flortaucipir uptake (SUVr) over time. Change = 18 months SUVr - baseline SUVr.

    Measured: baseline and 18 months

Secondary outcomes (2)
  1. Confirmatory Phase: Diagnostic Performance of Flortaucipir Visual Read

    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.

    Measured: baseline and 18 months

  2. Exploratory Phase: Correlation Between Flortaucipir SUVr and Age

    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.

    Measured: baseline scan

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Dec 2013 (estimated)
  2. Study startDec 2013
  3. Primary completion28 Jul 2017
  4. Study completion28 Jul 2017

Resources

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 2/3
Primary purpose
Diagnosis
Allocation
Non-randomised
Intervention model
Sequential
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 blind
Who is masked
Outcomes assessor
Enrolment
383 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02016560
Sponsor's protocol ID
18F-AV-1451-A05
Acronym
MCI
Status last verified
Sep 2020
First submitted
16 Dec 2013
Last updated
22 Sep 2020
Data monitoring committee
No

Publications

  • Lu M, Pontecorvo MJ, Devous MD Sr, Arora AK, Galante N, McGeehan A, Devadanam C, Salloway SP, Doraiswamy PM, Curtis C, Truocchio SP, Flitter M, Locascio T, Devine M, Zimmer JA, Fleisher AS, Mintun MA; AVID Collaborators. Aggregated Tau Measured by Visual Interpretation of Flortaucipir Positron Emission Tomography and the Associated Risk of Clinical Progression of Mild Cognitive Impairment and Alzheimer Disease: Results From 2 Phase III Clinical Trials. JAMA Neurol. 2021 Apr 1;78(4):445-453. doi: 10.1001/jamaneurol.2020.5505.

    PubMed 33587110

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing florbetapir F 18, Flortaucipir F18 and Brain PET Scan in people with Alzheimer's Disease, run by Avid Radiopharmaceuticals at 27 sites in United States.

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 19 inclusion and 9 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: finished, as of the sponsor's last update on 22 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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 combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 24 Aug 2020). 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?

Confirmatory Phase: Relationship Between Neocortical Flortaucipir Uptake and the Subsequent Rate of Cognitive Decline (time frame: between baseline and 18 months). 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?

On the ClinicalTrials.gov record for NCT02016560, which also lists 1 linked publication.

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 22 Sep 2020.

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