Alzheimer Disease
Conditions
Keywords
Florbetaben, Amyloid beta-protein, Alzheimer's disease
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
Interventions
Single intravenous injection 1-5ml, 300 MBq (+/- 20%)
Sponsors
Life Molecular Imaging SA
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 90-110 minutes post injection (PET image acquisition) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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). | 90-110 minutes post injection (PET image acquisition) | 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. |
| 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). | 90-110 minutes post injection (PET image acquisition) | 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. |
| 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). | 90-110 minutes post injection (PET image acquisition) | 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. |
| Sensitivity and Specificity of the Subject Level Composite SUVR Calculated Based on Pathology Results. | 90-110 minutes post injection (PET image acquisition) | 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. |
| Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans | 90-110 minutes post injection (PET image acquisition) | 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. |
Countries
Australia, France, Germany, Japan, United States
Participant flow
Recruitment details
Subjects were screened at 15 study centers in Australia, Germany, France, Japan, and the U.S.
Participants by arm
| Arm | Count |
|---|---|
| Safety Analysis Set All study participants who received any amount of florbetaben were included in the safety analysis set. | 216 |
| Total | 216 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 90 |
| Overall Study | Lost to Follow-up | 6 |
| Overall Study | Most common: Study ended by sponsor | 77 |
| Overall Study | Withdrawal by Subject | 9 |
Baseline characteristics
| Characteristic | Safety Analysis Set |
|---|---|
| Age, Continuous | 74.4 years STANDARD_DEVIATION 15.4 |
| Baseline clinical diagnosis Alzheimer's Disease | 137 participants |
| Baseline clinical diagnosis Dementia with Lewy bodies | 5 participants |
| Baseline clinical diagnosis Healthy negative control | 11 participants |
| Baseline clinical diagnosis Healthy volunteers | 32 participants |
| Baseline clinical diagnosis Other dementia subject | 31 participants |
| BMI (kg/m^2) | 23.617 kg/m^2 STANDARD_DEVIATION 5.213 |
| Body weight | 64.95 kg STANDARD_DEVIATION 18.44 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 213 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 164.70 cm STANDARD_DEVIATION 12.34 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 55 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 159 Participants |
| Sex: Female, Male Female | 104 Participants |
| Sex: Female, Male Male | 112 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 48 / 216 | 22 / 91 | 14 / 34 |
| serious Total, serious adverse events | 12 / 216 | 0 / 91 | 0 / 34 |
Outcome results
Primary
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.
Time frame: 90-110 minutes post injection (PET image acquisition)
Population: All participants included in the Interim Analysis Set were included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sensitivity (Interim Analysis Set) | 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 | Occipital Cortex | 88.89 percentage of regions |
| Sensitivity (Interim Analysis Set) | 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 | Anterior Cingulate Cortex | 90.00 percentage of regions |
| Sensitivity (Interim Analysis Set) | 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 | Frontal Cortex | 85.71 percentage of regions |
| Sensitivity (Interim Analysis Set) | 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 | Posterior Cingulate Cortex | 81.82 percentage of regions |
| Sensitivity (Interim Analysis Set) | 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 | Hippocampus | 57.14 percentage of regions |
| Sensitivity (Interim Analysis Set) | 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 | Cerebellar Cortex | 0.00 percentage of regions |
| Sensitivity (Interim Analysis Set) | 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 | Total | 77.36 percentage of regions |
| Specificity (Interim Analysis Set) | 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 | Cerebellar Cortex | 100.00 percentage of regions |
| Specificity (Interim Analysis Set) | 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 | Total | 94.20 percentage of regions |
| Specificity (Interim Analysis Set) | 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 | Frontal Cortex | 95.00 percentage of regions |
| Specificity (Interim Analysis Set) | 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 | Occipital Cortex | 86.36 percentage of regions |
| Specificity (Interim Analysis Set) | 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 | Hippocampus | 100.00 percentage of regions |
| Specificity (Interim Analysis Set) | 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 | Anterior Cingulate Cortex | 85.71 percentage of regions |
| Specificity (Interim Analysis Set) | 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 | Posterior Cingulate Cortex | 94.44 percentage of regions |
Comparison: For the primary analysis, point estimates together with normal-approximated, two sided 95% confidence intervals, were given for sensitivity in beta-amyloid detection based on the majority read.~The following hypothesis was formulated for sensitivity:~H0,sens: sensitivity ≤ 0.6 vs. H1, sens: sensitivity \> 0.6 H0,sens was to be rejected if the lower bound of the two-sided 95% CI is larger than 0.695% CI: [0.654, 0.894]
Comparison: For the primary analysis, point estimates together with normal-approximated, two sided 95% confidence intervals, were given for specificity in amyloid detection based on the majority read.~The following hypothesis was formulated for specificity:~H0,spec: specificity ≤ 0.8 vs. H1, spec: specificity \> 0.8 H0,spec was to be rejected if the lower bound of the two-sided 95% CI is larger than 0.895% CI: [0.886, 0.998]
Secondary
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.
Time frame: 90-110 minutes post injection (PET image acquisition)
Population: 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 and immunohistochemistry (SOT 2).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sensitivity (Interim Analysis Set) | 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 | 96.72 percentage of subjects |
| Sensitivity (Interim Analysis Set) | 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). | Specificity | 94.44 percentage of subjects |
Secondary
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.
Time frame: 90-110 minutes post injection (PET image acquisition)
Population: Sensitivity and Specificity of the Majority Read Whole Brain Visual Assessment in Detecting/Excluding Cerebral β-amyloid Plaques Compared with the Histopathological Verification according to CERAD Criteria (SOT 3).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sensitivity (Interim Analysis Set) | 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 | 96.49 percentage of subjects |
| Sensitivity (Interim Analysis Set) | 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). | Specificity | 85.00 percentage of subjects |
Secondary
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.
Time frame: 90-110 minutes post injection (PET image acquisition)
Population: Sensitivity and Specificity of the Majority Read Whole Brain Visual Assessment in Detecting/Excluding Cerebral β-amyloid Plaques Compared with the Histopathological Verification with Bielschowsky silver staining (SOT 1).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sensitivity (Interim Analysis Set) | 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 | 96.49 percentage of subjects |
| Sensitivity (Interim Analysis Set) | 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). | Specificity | 85.00 percentage of subjects |
Secondary
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.
Time frame: 90-110 minutes post injection (PET image acquisition)
Population: Sensitivity and Specificity of the subject level Composite SUVR with three different SOTs.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sensitivity (Interim Analysis Set) | Sensitivity and Specificity of the Subject Level Composite SUVR Calculated Based on Pathology Results. | SOT 3 (initial period) | 89 percentage of subjects |
| Sensitivity (Interim Analysis Set) | Sensitivity and Specificity of the Subject Level Composite SUVR Calculated Based on Pathology Results. | SOT 1 (last available scan) | 88 percentage of subjects |
| Sensitivity (Interim Analysis Set) | Sensitivity and Specificity of the Subject Level Composite SUVR Calculated Based on Pathology Results. | SOT 2 (last available scan) | 89 percentage of subjects |
| Sensitivity (Interim Analysis Set) | Sensitivity and Specificity of the Subject Level Composite SUVR Calculated Based on Pathology Results. | SOT 3 (last available scan) | 95 percentage of subjects |
| Sensitivity (Interim Analysis Set) | Sensitivity and Specificity of the Subject Level Composite SUVR Calculated Based on Pathology Results. | SOT 1 (initial period) | 89 percentage of subjects |
| Sensitivity (Interim Analysis Set) | Sensitivity and Specificity of the Subject Level Composite SUVR Calculated Based on Pathology Results. | SOT 2 (initial period) | 90 percentage of subjects |
| Specificity (Interim Analysis Set) | Sensitivity and Specificity of the Subject Level Composite SUVR Calculated Based on Pathology Results. | SOT 1 (initial period) | 82 percentage of subjects |
| Specificity (Interim Analysis Set) | Sensitivity and Specificity of the Subject Level Composite SUVR Calculated Based on Pathology Results. | SOT 3 (initial period) | 90 percentage of subjects |
| Specificity (Interim Analysis Set) | Sensitivity and Specificity of the Subject Level Composite SUVR Calculated Based on Pathology Results. | SOT 3 (last available scan) | 87 percentage of subjects |
| Specificity (Interim Analysis Set) | Sensitivity and Specificity of the Subject Level Composite SUVR Calculated Based on Pathology Results. | SOT 1 (last available scan) | 85 percentage of subjects |
| Specificity (Interim Analysis Set) | Sensitivity and Specificity of the Subject Level Composite SUVR Calculated Based on Pathology Results. | SOT 2 (initial period) | 91 percentage of subjects |
| Specificity (Interim Analysis Set) | Sensitivity and Specificity of the Subject Level Composite SUVR Calculated Based on Pathology Results. | SOT 2 (last available scan) | 94 percentage of subjects |
Secondary
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.
Time frame: 90-110 minutes post injection (PET image acquisition)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sensitivity (Interim Analysis Set) | Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans | SOT 1 (abeta absent) | 1.296 Standardized Uptake Value Ratio (SUVR) | Standard Deviation 0.232 |
| Sensitivity (Interim Analysis Set) | Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans | SOT 1 (abeta present) | 1.707 Standardized Uptake Value Ratio (SUVR) | Standard Deviation 0.276 |
| Sensitivity (Interim Analysis Set) | Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans | SOT 2 (abeta absent) | 1.237 Standardized Uptake Value Ratio (SUVR) | Standard Deviation 0.14 |
| Sensitivity (Interim Analysis Set) | Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans | SOT 2 (abeta present) | 1.714 Standardized Uptake Value Ratio (SUVR) | Standard Deviation 0.273 |
| Sensitivity (Interim Analysis Set) | Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans | SOT 3 (abeta absent) | 1.263 Standardized Uptake Value Ratio (SUVR) | Standard Deviation 0.17 |
| Sensitivity (Interim Analysis Set) | Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans | SOT 3 (abeta present) | 1.729 Standardized Uptake Value Ratio (SUVR) | Standard Deviation 0.27 |
| Specificity (Interim Analysis Set) | Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans | SOT 3 (abeta present) | 1.639 Standardized Uptake Value Ratio (SUVR) | Standard Deviation 0.236 |
| Specificity (Interim Analysis Set) | Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans | SOT 1 (abeta absent) | 1.319 Standardized Uptake Value Ratio (SUVR) | Standard Deviation 0.414 |
| Specificity (Interim Analysis Set) | Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans | SOT 2 (abeta present) | 1.632 Standardized Uptake Value Ratio (SUVR) | Standard Deviation 0.244 |
| Specificity (Interim Analysis Set) | Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans | SOT 3 (abeta absent) | 1.260 Standardized Uptake Value Ratio (SUVR) | Standard Deviation 0.39 |
| Specificity (Interim Analysis Set) | Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans | SOT 1 (abeta present) | 1.625 Standardized Uptake Value Ratio (SUVR) | Standard Deviation 0.25 |
| Specificity (Interim Analysis Set) | Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans | SOT 2 (abeta absent) | 1.175 Standardized Uptake Value Ratio (SUVR) | Standard Deviation 0.364 |
| 2nd Repeat Drug Administration | Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans | SOT 1 (abeta present) | 1.699 Standardized Uptake Value Ratio (SUVR) | Standard Deviation 0.046 |
| 2nd Repeat Drug Administration | Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans | SOT 2 (abeta absent) | 1.537 Standardized Uptake Value Ratio (SUVR) | — |
| 2nd Repeat Drug Administration | Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans | SOT 3 (abeta present) | 1.645 Standardized Uptake Value Ratio (SUVR) | Standard Deviation 0.099 |
| 2nd Repeat Drug Administration | Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans | SOT 2 (abeta present) | 1.699 Standardized Uptake Value Ratio (SUVR) | Standard Deviation 0.046 |
| 2nd Repeat Drug Administration | Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans | SOT 1 (abeta absent) | 1.537 Standardized Uptake Value Ratio (SUVR) | — |
| 2nd Repeat Drug Administration | Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans | SOT 3 (abeta absent) | NA Standardized Uptake Value Ratio (SUVR) | — |