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| ID | Type | Description | Link |
|---|---|---|---|
| 2007-002256-42 | EudraCT Number | ||
| 311741 | Other Identifier | company internal |
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The aim of this study is to evaluate the efficacy, safety of a single dose of BAY 94-9172 (ZK 6013443) as an investigational medicinal product (IMP) in detecting cerebral protein-plaque (amyloid beta) with positron emission tomography (PET). IMP binds to amyloidal beta protein accumulating in brain tissue already from early stages of Alzheimer's disease (AD). IMP is therefore a potential tracer to be used for detecting amyloid plaques. For each subject it is required to visit the study centre during the screening phase, on the PET imaging day and for 1 follow-up visit on the next day. A telephone call for safety follow-up will be performed 7 days after IMP administration. During the screening phase the subject's medical, neurological and surgical history, specific laboratory tests related to AD, MRI of the brain and certain neuro-psychiatric tests will be performed. Clinical safety measures (physical examinations, vital signs, electrocardiogram (ECG) and laboratory tests) will be performed on the PET imaging day before IMP injection and monitored during and after two PET imaging sessions. Clinical safety measures will be performed again on the follow-up visit next day. The results of PET imaging with IMP will be compared between probable AD patients and healthy volunteers (HV). The clinical diagnosis is based on international validated and accepted criteria and established after comprehensive clinical and neuro-psychiatric examinations
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Florbetaben (BAY94-9172) | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Florbetaben (BAY94-9172) | Drug | Healthy volunteers and patients with probable Alzheimer's disease receiving single injection of investigational medicinal product BAY 94-9172 followed by subsequent PET imaging sessions |
| Measure | Description | Time Frame |
|---|---|---|
| Specificity and Sensitivity of Florbetaben PET Scans Obtained in Part A Using Two Separate Algorithms and the Onsite Clinical Diagnosis as the Standard of Truth | Part A: For the calculation of sensitivity/specificity, a patient with probable AD was expected to have a positive florbetaben PET scan which was considered a match for sensitivity. A HV was expected to have a negative florbetaben PET scan which was considered a match for specificity. Standard of truth was the onsite clinical diagnosis. Two Beta-Amyloid Plaque Load (BAPL) algorithms for assessing the normality/abnormality of beta-amyloid plaque load in the brain scans were used. Using algorithm A (Majority Read), a brain scan of a subject with a BAPL score of "1" (without beta-amyloid plaque load) or "2" (with minor beta-amyloid plaque load) was considered normal and a BAPL score of "3" (with significant beta-amyloid plaque load) was considered abnormal. Using algorithm B (Average), a brain scan of a subject with a BAPL score of "1" was considered normal and a brain scan with a BAPL score of "2" or "3" was considered abnormal. Algorithm B was used in Part B and in the final | 90 - 110 min after investigational medical product (IMP) injection |
| Specificity and Sensitivity of Florbetaben PET Scans Obtained in Part B Using Two Separate Algorithms and the Onsite Clinical Diagnosis as the Standard of Truth. | Part B: For the calculation of sensitivity/specificity, a patient with probable AD was expected to have a positive florbetaben PET scan, ie,abnormal scan (BAPL scores "2" or "3") which was considered a match for sensitivity. A HV was expected to have a negative florbetaben PET scan, ie,normal scan (BAPL score "1") which was considered a match for specificity. The clinical diagnosis was established by an independent consensus panel (CP) of experts in dementia. Two independent sets of PET data reads were performed. The first set was performed by a panel of three readers who received live, instructor-led training on the visual assessment procedure. The second set was performed by a panel of five separate readers who were trained on the visual assessment procedure with electronic media. | 90 - 110 min after IMP injection |
| Measure | Description | Time Frame |
|---|---|---|
| Sensitivity and Specificity for All Participants Using Two Additional Imaging Windows for the Visual Assessment | PET scans from two additional imaging windows (45-60 min and 110-130 min) were visually assessed | 45 - 60 min and 110 - 130 min after IMP injection |
| Kappa Coefficient as a Measure of Agreement Between Readers Concerning the Visual Assessment of Abnormality of the Brain Scan (Based on BAPL Score) |
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Inclusion Criteria:
Each subject / Healthy volunteer (HV) who meets the following criteria will be eligible for enrollment into the study:
Inclusion criteria for HV only:
Inclusion criteria for patients with AD only:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bayer Study Director | Bayer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sun City | Arizona | 85351 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21481640 | Result | Barthel H, Gertz HJ, Dresel S, Peters O, Bartenstein P, Buerger K, Hiemeyer F, Wittemer-Rump SM, Seibyl J, Reininger C, Sabri O; Florbetaben Study Group. Cerebral amyloid-beta PET with florbetaben (18F) in patients with Alzheimer's disease and healthy controls: a multicentre phase 2 diagnostic study. Lancet Neurol. 2011 May;10(5):424-35. doi: 10.1016/S1474-4422(11)70077-1. Epub 2011 Apr 8. | |
| 33773598 |
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Part A screened 214 subjects; 113 AD and 101 HV. There were 63 screen failures (40 for inclusion criteria, 14 withdrew consent, 9 for other reasons) and one dropout prior to receiving study drug.
Part B screened 392 subjects; 204 AD and 188 HV. There were 118 screen failures for similar reasons and 2 dropouts prior to receiving study drug.
There were two parts in this study, Part A and Part B. Part A was conducted in Australia, Germany, Switzerland and USA. Subjects were recruited from 17 centers. HVs were age matched to subjects with probable Alzheimer's (AD).
Part B was conducted in Australia, Germany, Japan, Switzerland, and USA, subjects recruited from 22 centers.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A Healthy Volunteers | Florbetaben (BAY94-9172) : Healthy volunteers receiving 300 megabequerel (MBq) single injection of investigational medicinal product BAY 94-9172 followed by subsequent PET imaging sessions. |
| FG001 | Part A Alzheimer Patients |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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The agreement between 3 blinded readers concerning the visual assessment of abnormality of the brain scan (based on BAPL score) was measured by the kappa coefficient. Kappa values close to 1.0 indicate a high agreement while values close to 0 indicate random agreement. |
| 45-60 min, 90-110 min, 110-130 min |
| Standard Uptake Value Ratios for Florbetaben Signal | The Standard Uptake Value Ratios for florbetaben signal in the frontal cortex, lateral temporal cortex, parietal cortex, anterior cingulate, posterior cingulate cortex, occipital cortex, and cerebellum (white matter) were determined as a quantitative measure of tracer uptake. The SUV is defined as the ratio of (1) the tissue radioactivity concentration c (in MBq/kg) at time point t, and (2) the injected activity (in MBq, extrapolated to the same time t) divided by the body weight (in kg). These SUV numbers from regions of interest were then used to derive SUV ratios (SUVR) using the SUV from the cerebellar cortex as reference.) | 90-110 min post injection |
| Stanford |
| California |
| 94305 |
| United States |
| New Haven | Connecticut | 06510 | United States |
| New York | New York | 10016 | United States |
| New York | New York | 10032 | United States |
| The Bronx | New York | 10461 | United States |
| Providence | Rhode Island | 02906 | United States |
| Westmead | New South Wales | 2145 | Australia |
| Adelaide | South Australia | 5000 | Australia |
| Heidelberg | Victoria | 3084 | Australia |
| Erlangen | Bavaria | 91054 | Germany |
| München | Bavaria | 81377 | Germany |
| München | Bavaria | 81675 | Germany |
| Essen | North Rhine-Westphalia | 45122 | Germany |
| Jülich | North Rhine-Westphalia | 52425 | Germany |
| Münster | North Rhine-Westphalia | 48149 | Germany |
| Dresden | Saxony | 01307 | Germany |
| Leipzig | Saxony | 04103 | Germany |
| Berlin | State of Berlin | 13125 | Germany |
| Kobe | Hyōgo | 650-0017 | Japan |
| Kobe | Hyōgo | 650-0047 | Japan |
| Bunkyo-ku | Tokyo | 113-8603 | Japan |
| Zurich | Canton of Zurich | 8091 | Switzerland |
| Derived |
| Bullich S, Roe-Vellve N, Marquie M, Landau SM, Barthel H, Villemagne VL, Sanabria A, Tartari JP, Sotolongo-Grau O, Dore V, Koglin N, Muller A, Perrotin A, Jovalekic A, De Santi S, Tarraga L, Stephens AW, Rowe CC, Sabri O, Seibyl JP, Boada M. Early detection of amyloid load using 18F-florbetaben PET. Alzheimers Res Ther. 2021 Mar 27;13(1):67. doi: 10.1186/s13195-021-00807-6. |
Florbetaben (BAY94-9172) : Patients with probable Alzheimer's disease receiving 300 MBq single injection of investigational medicinal product BAY 94-9172 followed by subsequent PET imaging sessions |
| FG002 | Part B Healthy Volunteers | Florbetaben (BAY94-9172) : Healthy volunteers receiving 300 MBq single injection of investigational medicinal product BAY 94-9172 followed by subsequent PET imaging sessions |
| FG003 | Part B Alzheimer Patients | Florbetaben (BAY94-9172) : Patients with probable Alzheimer's disease receiving 300 MBq single injection of investigational medicinal product BAY 94-9172 followed by subsequent PET imaging sessions |
| COMPLETED |
|
| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A Healthy Volunteers | Florbetaben (BAY94-9172) : Healthy volunteers receiving single injection of investigational medicinal product BAY 94-9172 followed by subsequent PET imaging sessions |
| BG001 | Part A Alzheimer Patients | Florbetaben (BAY94-9172) : Patients with probable Alzheimer's disease receiving 300 MBq single injection of investigational medicinal product BAY 94-9172 followed by subsequent PET imaging sessions |
| BG002 | Part B Healthy Volunteers | Florbetaben (BAY94-9172) : Healthy volunteers receiving single injection of investigational medicinal product BAY 94-9172 followed by subsequent PET imaging sessions |
| BG003 | Part B Alzheimer Patients | Florbetaben (BAY94-9172) : Patients with probable Alzheimer's disease receiving 300 MBq single injection of investigational medicinal product BAY 94-9172 followed by subsequent PET imaging sessions |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Specificity and Sensitivity of Florbetaben PET Scans Obtained in Part A Using Two Separate Algorithms and the Onsite Clinical Diagnosis as the Standard of Truth | Part A: For the calculation of sensitivity/specificity, a patient with probable AD was expected to have a positive florbetaben PET scan which was considered a match for sensitivity. A HV was expected to have a negative florbetaben PET scan which was considered a match for specificity. Standard of truth was the onsite clinical diagnosis. Two Beta-Amyloid Plaque Load (BAPL) algorithms for assessing the normality/abnormality of beta-amyloid plaque load in the brain scans were used. Using algorithm A (Majority Read), a brain scan of a subject with a BAPL score of "1" (without beta-amyloid plaque load) or "2" (with minor beta-amyloid plaque load) was considered normal and a BAPL score of "3" (with significant beta-amyloid plaque load) was considered abnormal. Using algorithm B (Average), a brain scan of a subject with a BAPL score of "1" was considered normal and a brain scan with a BAPL score of "2" or "3" was considered abnormal. Algorithm B was used in Part B and in the final | All subjects who had PET imaging data and did not have a major protocol violation were included in the analysis.(n=146) | Posted | Number | 95% Confidence Interval | percentage of subjects | 90 - 110 min after investigational medical product (IMP) injection |
|
|
| |||||||||||||||||||||||||||||||||||
| Primary | Specificity and Sensitivity of Florbetaben PET Scans Obtained in Part B Using Two Separate Algorithms and the Onsite Clinical Diagnosis as the Standard of Truth. | Part B: For the calculation of sensitivity/specificity, a patient with probable AD was expected to have a positive florbetaben PET scan, ie,abnormal scan (BAPL scores "2" or "3") which was considered a match for sensitivity. A HV was expected to have a negative florbetaben PET scan, ie,normal scan (BAPL score "1") which was considered a match for specificity. The clinical diagnosis was established by an independent consensus panel (CP) of experts in dementia. Two independent sets of PET data reads were performed. The first set was performed by a panel of three readers who received live, instructor-led training on the visual assessment procedure. The second set was performed by a panel of five separate readers who were trained on the visual assessment procedure with electronic media. | All subjects who had PET imaging data and did not have a major protocol violation were included in the analysis | Posted | Number | 95% Confidence Interval | percentage of subjects | 90 - 110 min after IMP injection |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Sensitivity and Specificity for All Participants Using Two Additional Imaging Windows for the Visual Assessment | PET scans from two additional imaging windows (45-60 min and 110-130 min) were visually assessed | All subjects who had PET imaging data and did not have a major protocol violation were included in the analysis | Posted | Number | 95% Confidence Interval | percentage of subjects | 45 - 60 min and 110 - 130 min after IMP injection |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Kappa Coefficient as a Measure of Agreement Between Readers Concerning the Visual Assessment of Abnormality of the Brain Scan (Based on BAPL Score) | The agreement between 3 blinded readers concerning the visual assessment of abnormality of the brain scan (based on BAPL score) was measured by the kappa coefficient. Kappa values close to 1.0 indicate a high agreement while values close to 0 indicate random agreement. | All subjects who had PET imaging data and did not have a major protocol violation were included in the analysis | Posted | Number | Kappa coefficient | 45-60 min, 90-110 min, 110-130 min |
| ||||||||||||||||||||||||||||||||||||||
| Secondary | Standard Uptake Value Ratios for Florbetaben Signal | The Standard Uptake Value Ratios for florbetaben signal in the frontal cortex, lateral temporal cortex, parietal cortex, anterior cingulate, posterior cingulate cortex, occipital cortex, and cerebellum (white matter) were determined as a quantitative measure of tracer uptake. The SUV is defined as the ratio of (1) the tissue radioactivity concentration c (in MBq/kg) at time point t, and (2) the injected activity (in MBq, extrapolated to the same time t) divided by the body weight (in kg). These SUV numbers from regions of interest were then used to derive SUV ratios (SUVR) using the SUV from the cerebellar cortex as reference.) | All subjects who had PET imaging data and did not have a major protocol violation were included in the analysis | Posted | Mean | Standard Deviation | ratio | 90-110 min post injection |
|
A maximum of 64 days. Up to 56 days during the screening process and 8 days from baseline to second follow-up visit.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A Healthy Volunteers | Florbetaben (BAY94-9172) : Patients with probable Alzheimer's disease receiving single injection of investigational medicinal product BAY 94-9172 followed by subsequent PET imaging sessions | 1 | 69 | 10 | 69 | ||
| EG001 | Part A Alzheimer Patients | Florbetaben (BAY94-9172) : Healthy volunteers receiving single injection of investigational medicinal product BAY 94-9172 followed by subsequent PET imaging sessions | 1 | 81 | 3 | 81 | ||
| EG002 | Part B Healthy Volunteers | Florbetaben (BAY94-9172) : Patients with probable Alzheimer's disease receiving single injection of investigational medicinal product BAY 94-9172 followed by subsequent PET imaging sessions | 2 | 125 | 17 | 125 | ||
| EG003 | Part B Alzheimer Patients | Florbetaben (BAY94-9172) : Healthy volunteers receiving single injection of investigational medicinal product BAY 94-9172 followed by subsequent PET imaging sessions | 0 | 147 | 23 | 147 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Syncope | Nervous system disorders | MedDRA (13.1) | Systematic Assessment |
| |
| Arrhythmia | Cardiac disorders | MedDRA (13.1) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (13.1) | Systematic Assessment |
| |
| Clear cell endometrial carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (13.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Application site erythema | General disorders | MedDRA (13.1) | Systematic Assessment |
| |
| Injection site erythema | General disorders | MedDRA (13.1) | Systematic Assessment |
| |
| Injection site haematoma | General disorders | MedDRA (13.1) | Systematic Assessment |
| |
| Injection site irritation | General disorders | MedDRA (13.1) | Systematic Assessment |
| |
| Injection site pain | General disorders | MedDRA (13.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (13.1) | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (13.1) | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA (13.1) | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Juergen Hirschfeld | Piramal Imaging | 49 30 461 1246 15 | juergen.hirschfeld@piramal.com |
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D058225 | Plaque, Amyloid |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C527756 | 4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene |
Not provided
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| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Australia |
|
| Germany |
|
| Switzerland |
|
| Japan |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
Kappa coefficient estimate for PET data collected 45-60 min post-injection in Part B |
| OG004 | Imaging Window 90-110 Min Part B | Kappa coefficient estimate for PET data collected 90-110 min post-injection in Part B |
| OG005 | Imaging Window 110-130 Min Part B | Kappa coefficient estimate for PET data collected 110-130 min post-injection in Part B. |
|
|
| OG003 | Healthy Volunteer (HV) Group (Part B) | All subjects that were confirmed by consensus panel as healthy volunteers |
|
|