Clinical trial NCT01020838: Phase III Study of Florbetaben (BAY94-9172) PET Imaging for Detection/Exclusion of Cerebral β-amyloid Compared to Histopathology
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alzheimer Disease
Keywords: Florbetaben
Amyloid beta-protein
Alzheimer's disease
Lead sponsor: Life Molecular Imaging SA
Sponsor class: INDUSTRY
First posted: 2009-11-26
Enrollment: 218
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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)

Primary outcomes:
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
timeFrame: 90-110 minutes post injection (PET image acquisition)
Secondary outcomes:
measure: 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).
timeFrame: 90-110 minutes post injection (PET image acquisition)
measure: 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).
timeFrame: 90-110 minutes post injection (PET image acquisition)
measure: 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).
timeFrame: 90-110 minutes post injection (PET image acquisition)
measure: Sensitivity and Specificity of the Subject Level Composite SUVR Calculated Based on Pathology Results.
timeFrame: 90-110 minutes post injection (PET image acquisition)
measure: Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans
timeFrame: 90-110 minutes post injection (PET image acquisition)
Other outcomes:
Locations:
city: Sun City
country: United States
state: Arizona
city: Stanford
country: United States
state: California
city: Tampa
country: United States
state: Florida
city: Teaneck
country: United States
state: New Jersey
city: Philadelphia
country: United States
state: Pennsylvania
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Heidelberg
country: Australia
state: Victoria
city: Lille
country: France
city: Strasbourg
country: France
city: Jülich
country: Germany
state: Nordrhein-Westfalen
city: Leipzig
country: Germany
state: Sachsen
city: Toyohashi
country: Japan
state: Aichi
city: Toyohashi
country: Japan
state: Aichi
city: Toyohashi
country: Japan
state: Aichi
city: Isezaki
country: Japan
state: Gunma
city: Hamamatsu
country: Japan
state: Shizuoka
city: Itabashi-ku
country: Japan
state: Tokyo
Study officials:
affiliation: Life Molecular Imaging SA
name: Piramal Imaging SA Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.