Fase III-studie van florbetaben (BAY94-9172) PET-beeldvorming voor detectie/uitsluiting van cerebrale β-amyloïde in vergelijking met histopathologie
Een open-label, niet-gerandomiseerd onderzoek om de werkzaamheid en veiligheid van BAY94-9172 (ZK 6013443) Positronemissietomografie (PET)-beeldvorming voor detectie/uitsluiting van cerebrale bèta-amyloïde te evalueren in vergelijking met postmortale histopathologie
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
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 3
Contacten en locaties
Studie Locaties
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Victoria
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Heidelberg, Victoria, Australië, 3084
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North Rhine-Westphalia
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Jülich, North Rhine-Westphalia, Duitsland, 52425
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Saxony
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Leipzig, Saxony, Duitsland, 04103
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Lille, Frankrijk, 59037
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Strasbourg, Frankrijk, 67091
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Aichi-ken
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Toyohashi, Aichi-ken, Japan, 440-0045
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Toyohashi, Aichi-ken, Japan, 441-8021
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Toyohashi, Aichi-ken, Japan, 441-8124
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Gunma
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Isesaki, Gunma, Japan, 372-0006
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Shizuoka
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Hamamatsu, Shizuoka, Japan, 432-8580
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Tokyo
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tabashi City, Tokyo, Japan, 173-0015
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Arizona
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Sun City, Arizona, Verenigde Staten, 85351
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California
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Stanford, California, Verenigde Staten, 94305
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Florida
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Tampa, Florida, Verenigde Staten, 33616
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New Jersey
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Teaneck, New Jersey, Verenigde Staten, 07666
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Pennsylvania
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Philadelphia, Pennsylvania, Verenigde Staten, 19104
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Texas
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Dallas, Texas, Verenigde Staten, 75390
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Houston, Texas, Verenigde Staten, 77030
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San Antonio, Texas, Verenigde Staten, 78229
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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)
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Diagnostisch
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: Florbetaben (BAY94-9172)
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Single intravenous injection 1-5ml, 300 MBq (+/- 20%) |
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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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
Tijdsspanne: 90-110 minutes post injection (PET image acquisition)
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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". |
90-110 minutes post injection (PET image acquisition)
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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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).
Tijdsspanne: 90-110 minutes post injection (PET image acquisition)
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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". |
90-110 minutes post injection (PET image acquisition)
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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).
Tijdsspanne: 90-110 minutes post injection (PET image acquisition)
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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". |
90-110 minutes post injection (PET image acquisition)
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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).
Tijdsspanne: 90-110 minutes post injection (PET image acquisition)
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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". |
90-110 minutes post injection (PET image acquisition)
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Sensitivity and Specificity of the Subject Level Composite SUVR Calculated Based on Pathology Results.
Tijdsspanne: 90-110 minutes post injection (PET image acquisition)
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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. |
90-110 minutes post injection (PET image acquisition)
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Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans
Tijdsspanne: 90-110 minutes post injection (PET image acquisition)
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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. |
90-110 minutes post injection (PET image acquisition)
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Medewerkers en onderzoekers
Sponsor
Onderzoekers
- Studie directeur: Andrew Stephens, MD, PhD, Lantheus Germany GmbH
Publicaties en nuttige links
Algemene publicaties
- 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.
- 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.
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Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Hersenziekten
- Ziekten van het centrale zenuwstelsel
- Ziekten van het zenuwstelsel
- Psychische aandoening
- Pathologische aandoeningen, anatomisch
- Neurocognitieve stoornissen
- Dementie
- Tauopathieën
- Neurodegeneratieve ziekten
- Pathologische aandoeningen, tekenen en symptomen
- Ziekte van Alzheimer
- Plaque, amyloïde
- 4- (N-methylamino) -4 '-(2- (2- (2-fluoroethoxy) ethoxy) ethoxy) Stilbeen
Andere studie-ID-nummers
- 14595
- 2009-012569-79 (EudraCT-nummer)
- 2009 (Subsidie/contract van de Amerikaanse NIH)
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