Trial Outcomes & Findings for Phase II Study of Florbetaben (BAY94-9172) PET Imaging for Detection/Exclusion of Cerebral β-amyloid. (NCT NCT00928304)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

109 participants

Primary outcome timeframe

100-120 min

Results posted on

2014-03-05

Participant Flow

The study was conducted at two sites in the US.

A total of 130 subjects were screened. 21 subjects were considered as screen failures and were not enrolled into the study. 9 subjects did not meet the inclusion/exclusion criteria. 10 subjects withdrew their consent. 1 subject was lost to follow-up and 1 subjected exceeded the weight limit for the camera.

Participant milestones

Participant milestones
Measure	Down Syndrome Group 39 Down Syndrome subjects received Florbetaben (BAY94-9172) : 300 megabecquerels (MBq) single IV injection of 2 to 10 mL	Healthy Volunteer Group 70 healthy volunteer subjects received Florbetaben (BAY94-9172): 300 MBq single IV injection of 2 to 10 mL
Overall Study STARTED	39	70
Overall Study COMPLETED	39	70
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Subjects Enrolled in Study n=109 Participants All Down Syndrome and healthy volunteer subjects
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	109 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous Down Syndrome Group	46.3 years STANDARD_DEVIATION 4.7 • n=5 Participants
Age, Continuous Healthy Volunteer Group	27.7 years STANDARD_DEVIATION 5.1 • n=5 Participants
Sex: Female, Male Female	60 Participants n=5 Participants
Sex: Female, Male Male	49 Participants n=5 Participants
Region of Enrollment United States	109 participants n=5 Participants

PRIMARY outcome

Timeframe: 100-120 min

Population: All subjects in the down syndrome population and healthy volunteers were included in this analysis.

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.

Outcome measures

Outcome measures
Measure	Majority Read n=109 Participants Majority read of the visual assessment made by 3 independent readers of PET images from all subjects.	Majority Read (DS-Old) Majority Read results for Down Syndrome subjects with age \>46 yrs	Healthy Volunteer Group All healthy volunteers enrolled in the study
Sensitivity of the Independent Visual Assessment of Detecting Cerebral Amyloid-beta in Individuals With Down Syndrome and Specificity in Subjects Without Down Syndrome Sensitivity	46.15 percentage of subjects Interval 30.51 to 61.8	—	—
Sensitivity of the Independent Visual Assessment of Detecting Cerebral Amyloid-beta in Individuals With Down Syndrome and Specificity in Subjects Without Down Syndrome Specificity	100.00 percentage of subjects Interval 100.0 to 100.0	—	—

SECONDARY outcome

Timeframe: 100 - 120 min

Population: All Down Syndrome subjects (n=39) were analyzed for this outcome.

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.

Outcome measures

Outcome measures
Measure	Majority Read n=21 Participants Majority read of the visual assessment made by 3 independent readers of PET images from all subjects.	Majority Read (DS-Old) n=18 Participants Majority Read results for Down Syndrome subjects with age \>46 yrs	Healthy Volunteer Group All healthy volunteers enrolled in the study
Sensitivity Results in the Down Syndrome Age Subgroups	23.81 percentage of subjects Interval 5.59 to 42.03	72.22 percentage of subjects Interval 51.53 to 92.91	—

SECONDARY outcome

Timeframe: 100 - 120 min p.i.

Population: All Down Syndrome subjects and healthy volunteers enrolled in the study were included in this analysis

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.

Outcome measures

Outcome measures
Measure	Majority Read n=39 Participants Majority read of the visual assessment made by 3 independent readers of PET images from all subjects.	Majority Read (DS-Old) n=70 Participants Majority Read results for Down Syndrome subjects with age \>46 yrs	Healthy Volunteer Group All healthy volunteers enrolled in the study
Quantitative Parameters Standard Uptake Value Ratio posterior cingulate	1.525 SUVR Standard Deviation 0.2549	1.329 SUVR Standard Deviation 0.1118	—
Quantitative Parameters Standard Uptake Value Ratio lateral temporal cortex	1.350 SUVR Standard Deviation 0.2265	1.132 SUVR Standard Deviation 0.0623	—
Quantitative Parameters Standard Uptake Value Ratio parietal cortex	1.391 SUVR Standard Deviation 0.2594	1.138 SUVR Standard Deviation 0.0742	—
Quantitative Parameters Standard Uptake Value Ratio cerebellum, white matter	1.730 SUVR Standard Deviation 0.2115	1.769 SUVR Standard Deviation 0.1302	—
Quantitative Parameters Standard Uptake Value Ratio frontal cortex	1.396 SUVR Standard Deviation 0.2488	1.146 SUVR Standard Deviation 0.0749	—

SECONDARY outcome

Timeframe: 100 - 120 min

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.

Outcome measures

Outcome measures
Measure	Majority Read n=18 Participants Majority read of the visual assessment made by 3 independent readers of PET images from all subjects.	Majority Read (DS-Old) n=21 Participants Majority Read results for Down Syndrome subjects with age \>46 yrs	Healthy Volunteer Group n=70 Participants All healthy volunteers enrolled in the study
Consistency Between Visual and Quantitative Efficacy posterior cingulate	1.626 SUVR Standard Deviation 0.2372	1.438 SUVR Standard Deviation 0.2421	1.329 SUVR Standard Deviation 0.1118
Consistency Between Visual and Quantitative Efficacy lateral temporal cortex	1.498 SUVR Standard Deviation 0.2396	1.223 SUVR Standard Deviation 0.1092	1.132 SUVR Standard Deviation 0.0623
Consistency Between Visual and Quantitative Efficacy parietal cortex	1.557 SUVR Standard Deviation 0.2567	1.250 SUVR Standard Deviation 0.1620	1.138 SUVR Standard Deviation 0.0742
Consistency Between Visual and Quantitative Efficacy cerebellum, white matter	1.698 SUVR Standard Deviation 0.2396	1.758 SUVR Standard Deviation 0.1856	1.769 SUVR Standard Deviation 0.1302
Consistency Between Visual and Quantitative Efficacy frontal cortex	1.566 SUVR Standard Deviation 0.2372	1.249 SUVR Standard Deviation 0.1451	1.146 SUVR Standard Deviation 0.0749

Adverse Events

Down Syndrome Group

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Healthy Volunteer Group

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Down Syndrome Group n=39 participants at risk 39 Down Syndrome subjects received Florbetaben (BAY94-9172): 300 MBq single IV injection of 2 to 10 mL	Healthy Volunteer Group n=70 participants at risk 70 healthy volunteer subjects received Florbetaben (BAY94-9172): 300 MBq single IV injection of 2 to 10 mL
General disorders Injection site hematoma	5.1% 2/39 • Number of events 2 • 8 days Adverse event data were collected from Day 1 (baseline) until Day 8 (secondary follow-up visit)	1.4% 1/70 • Number of events 1 • 8 days Adverse event data were collected from Day 1 (baseline) until Day 8 (secondary follow-up visit)
Nervous system disorders Headache	0.00% 0/39 • 8 days Adverse event data were collected from Day 1 (baseline) until Day 8 (secondary follow-up visit)	7.1% 5/70 • Number of events 5 • 8 days Adverse event data were collected from Day 1 (baseline) until Day 8 (secondary follow-up visit)

Additional Information

Dr. Juergen Hirschfeld

Piramal Imaging

Phone: 49 30 461 1246 15

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60