Phase II Study of Florbetaben (BAY94-9172) PET Imaging for Detection/Exclusion of Cerebral β-amyloid.

Study Overview
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Brief Summary
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To determine the sensitivity of the visual assessment of BAY94-9172 PET images in detecting cerebral β-amyloid in individuals with Down Syndrome (DS) and specificity in individuals without DS. Given that individuals with Down Syndrome develop β-amyloid pathology over the age of 40, the clinical diagnosis of Down Syndrome will serve as the standard of truth.

Official Title
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An Open-Label, Non-Randomized Study to Evaluate the Efficacy and Safety of BAY94-9172 (ZK 6013443) Positron Emission Tomography (PET) for Detection of Cerebral ß-Amyloid in Individuals With Down Syndrome Compared to Individuals Without Down Syndrome

Conditions
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Down Syndrome, Amyloid Beta-protein

Intervention / Treatment
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* Drug: Florbetaben (BAY94-9172)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Study participants were individuals with DS and healthy volunteers (HVs). Main inclusion criteria for individuals without DS >=21 and <= 40 years of age Mini-Mental State Examination (MMSE) >= 28 Clinical Dementia Rating (CDR) of 0 Main inclusion criteria for individuals with DS >= 40 years of age Exclusion Criteria: Main exclusion criteria for both groups Unstable medical or psychiatric condition, study specific screening procedures with the understanding that the patient has the right to withdraw from the study at any time

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Florbetaben (BAY94-9172)<br> | Drug: Florbetaben (BAY94-9172)<br>* 300 megabecquerels (MBq) as single IV injection of 2 to 10 mL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of the Independent Visual Assessment of Detecting Cerebral Amyloid-beta in Individuals With Down Syndrome and Specificity in Subjects Without Down Syndrome | The primary variables are sensitivity (percentage of DS subjects positive for cerebral beta-amyloid) and specificity (percentage of healthy volunteers negative for cerebral beta-amyloid) of brain uptake of florbetaben based on the majority read of the visual assessment by three independent blinded readers of PET images obtained 100 to 120 minutes post-injection of florbetaben. | 100-120 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity Results in the Down Syndrome Age Subgroups | The majority read sensitivity (percentage of DS subjects positive for cerebral beta-amyloid by majority read) was computed for the group of DS subjects with age equal to or below the median age (DS-young) and for DS subjects with age above the median age (DS-old). The median age was 46 yrs, with 3 subjects being exactly 46 yrs old. As defined, these subjects were assigned to the DS-young group. | 100 - 120 min | 
| Quantitative Parameters Standard Uptake Value Ratio | The Standard Uptake Value Ratios for florbetaben signal in the frontal cortex, posterior cingulate, lateral temporal cortex, parietal 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. | 100 - 120 min p.i. | 
| Consistency Between Visual and Quantitative Efficacy | For a comparison of the results of the visual assessment with the quantitative assessment, descriptive Standardized Uptake Value Ratio (SUVR) statistics were computed separately for DS subjects with an abnormal/normal majority read of the PET scan (DS-PET+/DS-PET-). 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. | 100 - 120 min | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amyloid beta-protein, Down Syndrome