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

Purpose

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.

Condition	Intervention	Phase
Down Syndrome Amyloid Beta-protein	Drug: Florbetaben (BAY94-9172)	Phase 2


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Diagnostic
Official Title:	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

Resource links provided by NLM:

Genetics Home Reference related topics: CASK-related intellectual disability Down syndrome SYNGAP1-related intellectual disability

MedlinePlus related topics: Amyloidosis Down Syndrome

U.S. FDA Resources

Further study details as provided by Piramal Imaging SA:

Primary Outcome Measures:

Sensitivity of the Independent Visual Assessment of Detecting Cerebral Amyloid-beta in Individuals With Down Syndrome and Specificity in Subjects Without Down Syndrome [ Time Frame: 100-120 min ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Sensitivity Results in the Down Syndrome Age Subgroups [ Time Frame: 100 - 120 min ] [ Designated as safety issue: No ]
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.
Quantitative Parameters Standard Uptake Value Ratio [ Time Frame: 100 - 120 min p.i. ] [ Designated as safety issue: No ]
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.
Consistency Between Visual and Quantitative Efficacy [ Time Frame: 100 - 120 min ] [ Designated as safety issue: No ]
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.


Enrollment:	109
Study Start Date:	June 2009
Study Completion Date:	January 2011
Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Florbetaben (BAY94-9172)	Drug: Florbetaben (BAY94-9172) 300 megabecquerels (MBq) as single IV injection of 2 to 10 mL

Eligibility


Ages Eligible for Study:	21 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00928304

Locations


United States, Arizona

Sun City, Arizona, United States, 85351
United States, Connecticut

New Haven, Connecticut, United States, 06510

Sponsors and Collaborators

Piramal Imaging SA

Investigators


Study Director:	Bayer Study Director	Bayer

More Information

Additional Information:

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Responsible Party:	Piramal Imaging SA
ClinicalTrials.gov Identifier:	NCT00928304 History of Changes
Other Study ID Numbers:	14311
Study First Received:	June 24, 2009
Results First Received:	December 9, 2013
Last Updated:	January 29, 2014
Health Authority:	United States: Food and Drug Administration

Keywords provided by Piramal Imaging SA:


Amyloid beta-protein Down Syndrome

Additional relevant MeSH terms:


Syndrome Amyloidosis Down Syndrome Disease Pathologic Processes Proteostasis Deficiencies Metabolic Diseases Intellectual Disability	Neurobehavioral Manifestations Neurologic Manifestations Nervous System Diseases Abnormalities, Multiple Congenital Abnormalities Chromosome Disorders Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on September 23, 2016