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AzTrials

Alzheimer DiseasePhase 3NCT01020838

Phase III Study of Florbetaben (BAY94-9172) PET Imaging for Detection/Exclusion of Cerebral β-amyloid Compared to Histopathology

A Phase 3 study testing Florbetaben (BAY94-9172) in people with Alzheimer Disease, run by Lantheus Biosciences Ltd. at 19 sites in 5 countries.

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

To determine the sensitivity and specificity of the visual assessment of tracer uptake in the Florbetaben PET images compared to histological verification of the presence or absence of cerebral β-amyloid in the respective histopathologic post mortem specimens as the standard of truth Read more about this study

Who is it for?
Ages 21 years and older
Conditions the study is for
Alzheimer Disease
What is being tested?
Florbetaben (BAY94-9172)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
218 participants
Where
19 sitesin 5 countries
Study dates
Nov 2009to Dec 2013
Phase
Phase 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 21 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Females, no child-bearing potential or negative urine pregnancy test on day of BAY94-9172 injection
  • Exhibits visual, auditory, and communicative capabilities adequate to provide informed consent or assent and comply with study procedures
  • Is willing and able to lie down in magnetic resonance imaging (MRI) and positron emission tomography (PET) scanners
  • Is willing to donate their brain for postmortem examination in case of death
  • The subject, or the subject and/or legally acceptable representative will be compliant and have a high probability of completing the study in the opinion of the investigator
  • Has been fully informed about the study, including provisions of the Health Insurance Portability and Accountability Act (HIPAA), as applicable, and informed consent or assent has been signed and dated (with time) by the subject and/or the subject's legally acceptable representative
  • The subjects who have participated in a previous florbetaben study e.g. study 311741 may be included in the present study. The MRI- and florbetaben PET scan do not need to be repeated if both scans were performed within twelve months prior to inclusion.

Who cannot join

  • Has severe cerebral macrovascular (ie, multi-stroke) disease or brain tumor (metastasis/brain cancer) as verified by MRI
  • Has any contraindication to magnetic resonance imaging (MRI) examination, eg, metal implants or phobia as determined by the onsite radiologist performing the scan
  • Has been previously enrolled in this study or participated in a clinical study involving an investigational pharmaceutical product within 30 days prior to screening and/or was administered a radiopharmaceutical within 10 radioactive half-lives prior to study drug administration in this study
  • Has severe cardio-vascular instability requiring intensive care surveillance and/or therapeutic intervention (i.e. catecholamine infusion)

Trial locations and contacts

19 sites in 5 countries.

19 sites in 5 countries

United States8 sites

  • Study site

    Dallas, Texas, 75390

  • Study site

    Houston, Texas, 77030

  • Study site

    Philadelphia, Pennsylvania, 19104

  • Study site

    San Antonio, Texas, 78229

  • Study site

    Stanford, California, 94305

  • Study site

    Sun City, Arizona, 85351

  • Study site

    Tampa, Florida, 33616

  • Study site

    Teaneck, New Jersey, 07666

Other trials in United States

Japan6 sites

  • Study site

    Hamamatsu, Shizuoka, 432-8580

  • Study site

    Isesaki, Gunma, 372-0006

  • Study site

    tabashi City, Tokyo, 173-0015

  • Study site

    Toyohashi, Aichi-ken, 440-0045

  • Study site

    Toyohashi, Aichi-ken, 441-8021

  • Study site

    Toyohashi, Aichi-ken, 441-8124

Other trials in Japan

France2 sites

  • Study site

    Lille, 59037

  • Study site

    Strasbourg, 67091

Other trials in France

Germany2 sites

  • Study site

    Jülich, North Rhine-Westphalia, 52425

  • Study site

    Leipzig, Saxony, 04103

Other trials in Germany

Australia1 site

  • Study site

    Heidelberg, Victoria, 3084

Other trials in Australia

About this study

Official title: An Open-label, Non-randomized Study to Evaluate the Efficacy and Safety of BAY94-9172 (ZK 6013443) Positron Emission Tomography (PET) Imaging for Detection/Exclusion of Cerebral Beta-amyloid When Compared to Postmortem Histopathology

To determine the sensitivity and specificity of the visual assessment of tracer uptake in the Florbetaben PET images compared to histological verification of the presence or absence of cerebral β-amyloid in the respective histopathologic post mortem specimens as the standard of truth

Being tested
Florbetaben (BAY94-9172)
Keywords
Florbetaben, Amyloid beta-protein, Alzheimer's disease
Medical subject headings
Alzheimer Disease, Plaque, Amyloid

What participants receive

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

  • Florbetaben (BAY94-9172)Drug

    Single intravenous injection 1-5ml, 300 MBq (+/- 20%)

Study groups in NCT01020838
Study groupRoleWhat they receive
Florbetaben (BAY94-9172)ExperimentalNot described
Receives: Drug: Florbetaben (BAY94-9172)

What is being measured

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

  1. Sensitivity and Specificity of the Majority Read of Visual Assessment of Tracer Uptake Compared to Histological Verification of the Presence or Absence of Cerebral Beta-amyloid in Postmortem Specimens

    The sensitivity/specificity of the visual assessment were calculated based on the majority read assessment of regional tracer uptake. This result was derived from assessments by 3 independent readers for brain regions of a subject where a Standard of Truth (SOT) was available. The SOT for this analysis was a centralized histopathological determination of β-amyloid presence/absence based on both Bielschowsky silver and immunohistochemical staining. Based on the PET images, a brain region was classified as "normal" or "abnormal" depending on the presence or absence of regional tracer uptake in the respective region. "Normal" therefore meant absence of β-amyloid and "abnormal" presence of β-amyloid. Sensitivity was defined as the percentage of abnormal brain regions from all regions where an SOT was available and the SOT was "β-amyloid present". Specificity was defined as the percentage of normal brain regions from all regions where an SOT was available and was "β-amyloid not present".

    Measured: 90-110 minutes post injection (PET image acquisition)

Secondary outcomes (5)

  1. Sensitivity and Specificity of the Majority Read "Whole Brain" Visual Assessment in Detecting/Excluding Cerebral Neuritic β-amyloid Plaques Compared With the Histopathological Verification With Bielschowsky Silver Staining (SOT 1).

    Sensitivity and specificity of the whole brain visual assessment were calculated. Any brain with a region classified as abnormal from PET imaging was to be classified as abnormal for the "whole brain" assessment. This result was derived from assessments by 3 independent readers for a subject where a Standard of Truth (SOT) was available. The SOT for this analysis was based on a centralized histopathological assessment of the presence/absence of β-amyloid based on Bielschowsky silver staining (SOT 1).

    The sensitivity was defined as the proportion of brains classified as abnormal from all brains where this SOT was available and was "β-amyloid present". The specificity was defined as the proportion of brains classified as normal from all brains where this SOT was available and was "β-amyloid not present".

    Measured: 90-110 minutes post injection (PET image acquisition)

  2. Sensitivity and Specificity of the Majority Read "Whole Brain" Visual Assessment in Detecting/Excluding Cerebral Neuritic β-amyloid Plaques Compared With Histopathological Verification With Bielschowsky Silver Staining and Immunohistochemistry (SOT 2).

    Sensitivity and specificity of the whole brain visual assessment were calculated. Any brain with a region classified as abnormal from PET imaging was to be classified as abnormal for the "whole brain" assessment. This result was derived from assessments by 3 independent readers for a subject where a Standard of Truth (SOT) was available. The SOT for this analysis was based on a centralized histopathological assessment of the presence/absence of β-amyloid based on Bielschowsky silver staining and immunohistochemistry (SOT 2).

    The sensitivity was defined as the proportion of brains classified as abnormal from all brains where this SOT was available and was "β-amyloid present". The specificity was defined as the proportion of brains classified as normal from all brains where this SOT was available and was "β-amyloid not present".

    Measured: 90-110 minutes post injection (PET image acquisition)

  3. Sensitivity and Specificity of the Majority Read "Whole Brain" Visual Assessment in Detecting/Excluding Cerebral Neuritic β-amyloid Plaques Compared With the Histopathological Verification According to CERAD Criteria (SOT 3).

    Sensitivity and specificity of the whole brain visual assessment were calculated. Any brain with a region classified as abnormal from PET imaging was to be classified as abnormal for the "whole brain" assessment. This result was derived from assessments by 3 independent readers for a subject where a Standard of Truth (SOT) was available. The SOT for this analysis was based on a histopathological assessment of the presence/absence of β-amyloid according to CERAD Criteria (SOT 3).

    The sensitivity was defined as the proportion of brains classified as abnormal from all brains where this SOT was available and was "β-amyloid present". The specificity was defined as the proportion of brains classified as normal from all brains where this SOT was available and was "β-amyloid not present".

    Measured: 90-110 minutes post injection (PET image acquisition)

  4. Sensitivity and Specificity of the Subject Level Composite SUVR Calculated Based on Pathology Results.

    Sensitivity and specificity of subject level composite Standard Uptake Value Ratios (SUVR) by SOT for subjects with available brain tissue and 10 healthy volunteers. The SUVR were determined as a quantitative measure of tracer uptake. The SUV is defined as the ratio of the tissue radioactivity concentration c (in MBq/kg) at time point t, and the injected activity (in MBq), extrapolated to the same time (t) divided by the body weight (in kg). SUV numbers were then used to derive SUV ratios (SUVR) using the SUV from the cerebellar cortex as reference. SOTs comprised Bielschowsky silver staining (SOT 1), Bielschowsky silver staining with immunohistochemistry (SOT 2) and neuropathology assessment according to CERAD (SOT 3). SUVR analysis was performed for baseline and available follow-up scans. The optimal threshold for the distinction between β-amyloid present yes/no according to the respective SOT was derived based on ROC curve analyses and used to calculate sensitivity and specificity.

    Measured: 90-110 minutes post injection (PET image acquisition)

  5. Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans

    Subject level composite SUVRs (calculated as mean of SUVRs from the frontal, parietal, lateral temporal, anterior and posterior cingulate, and occipital cortices) by SOT are reported for subjects with available brain tissue. The initial drug administration group includes additionally 10 healthy controls who were considered as ß-amyloid negative. The SOTs for deceased subjects were based on Bielschowsky silver staining (SOT 1), Bielschowsky silver staining in combination with immunohistochemistry (SOT 2) and neuropathology assessment according to CERAD (SOT 3). SUVR analysis was performed for baseline and available follow-up scans.

    Measured: 90-110 minutes post injection (PET image acquisition)

Timeline

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

  1. First posted26 Nov 2009 (estimated)
  2. Study startNov 2009
  3. Primary completionSep 2011
  4. Study completionDec 2013

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 3
Primary purpose
Diagnosis
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
218 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01020838
Sponsor's protocol ID
14595
Other IDs
2009-012569-79, 2009
Status last verified
Apr 2016
First submitted
16 Nov 2009
Last updated
27 May 2016
Data monitoring committee
No

Publications

  • Seibyl J, Catafau AM, Barthel H, Ishii K, Rowe CC, Leverenz JB, Ghetti B, Ironside JW, Takao M, Akatsu H, Murayama S, Bullich S, Mueller A, Koglin N, Schulz-Schaeffer WJ, Hoffmann A, Sabbagh MN, Stephens AW, Sabri O. Impact of Training Method on the Robustness of the Visual Assessment of 18F-Florbetaben PET Scans: Results from a Phase-3 Study. J Nucl Med. 2016 Jun;57(6):900-6. doi: 10.2967/jnumed.115.161927. Epub 2016 Jan 28.

    PubMed 26823561

  • Sabri O, Sabbagh MN, Seibyl J, Barthel H, Akatsu H, Ouchi Y, Senda K, Murayama S, Ishii K, Takao M, Beach TG, Rowe CC, Leverenz JB, Ghetti B, Ironside JW, Catafau AM, Stephens AW, Mueller A, Koglin N, Hoffmann A, Roth K, Reininger C, Schulz-Schaeffer WJ; Florbetaben Phase 3 Study Group. Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease: phase 3 study. Alzheimers Dement. 2015 Aug;11(8):964-74. doi: 10.1016/j.jalz.2015.02.004. Epub 2015 Mar 28.

    PubMed 25824567

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Florbetaben (BAY94-9172) in people with Alzheimer Disease, run by Lantheus Biosciences Ltd. at 19 sites in 5 countries.

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 7 inclusion and 4 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 27 May 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States, Japan, France, Germany, Australia. 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 phase mean?

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 25 Mar 2015). 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?

Sensitivity and Specificity of the Majority Read of Visual Assessment of Tracer Uptake Compared to Histological Verification of the Presence or Absence of Cerebral Beta-amyloid in Postmortem Specimens (time frame: 90-110 minutes post injection (PET image acquisition)). 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 NCT01020838, which also lists 2 linked publications.

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 27 May 2016.

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