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

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

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.

Study Overview

• Status: Completed
• Conditions: Down Syndrome; Amyloid Beta-protein
• Intervention / Treatment: Drug: Florbetaben (BAY94-9172)

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Sun City, Arizona, United States, 85351
  • Connecticut
    • New Haven, Connecticut, United States, 06510

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Life Molecular Imaging SA

Publications and helpful links

General Publications

• Bullich S, Roé-Vellvé N, Marquié M, Landau SM, Barthel H, Villemagne VL, Sanabria Á, Tartari JP, Sotolongo-Grau O, Doré V, Koglin N, Müller A, Perrotin A, Jovalekic A, De Santi S, Tárraga L, Stephens AW, Rowe CC, Sabri O, Seibyl JP, Boada M. Early detection of amyloid load using (18)F-florbetaben PET. Alzheimers Res Ther. 2021 Mar 27;13(1):67. doi: 10.1186/s13195-021-00807-6.

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: June 24, 2009
• First Submitted That Met QC Criteria: June 24, 2009
• First Posted (Estimate): June 25, 2009

Study Record Updates

• Last Update Posted (Estimate): March 5, 2014
• Last Update Submitted That Met QC Criteria: January 29, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Down Syndrome; Amyloid beta-protein
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Proteostasis Deficiencies; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Syndrome; Amyloidosis; Down Syndrome
• Other Study ID Numbers: 14311