Trial Outcomes & Findings for Phase III Study of the Correlation Between Florbetapir F18 PET Imaging and Amyloid Pathology in the Brain (NCT NCT00857415)

NCT ID: NCT00857415

Last Updated: 2012-05-22

Results Overview

Spearman's rank order correlation of the median semi-quantitative visual read of the florbetapir-PET image and the amyloid plaque density assessed post-mortem by quantitative immunohistochemistry (IHC) averaged across 6 brain regions (precuneus, parietal cortex, frontal cortex, temporal cortex, posterior cingulate, anterior cingulate). Spearman's rank order correlation ranges from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

226 participants

Primary outcome timeframe

at autopsy up to 12 months post-scan

Results posted on

2012-05-22

Participant Flow

Participant milestones

Participant milestones
Measure
Autopsy Cohort
End-of-life subjects consenting to brain donation at autopsy. Subjects received a single intravenous injection of 370 MBq florbetapir followed by a 10-minute PET scan 50 minutes post-injection.
Specificity Cohort
Younger healthy controls presumed to be devoid of beta-amyloid plaques. Subjects received a single intravenous injection of 370 MBq florbetapir followed by a 10-minute PET scan 50 minutes post-injection.
Overall Study
STARTED
152
74
Overall Study
Deceased Within One Year of AV-45 Scan
37
0
Overall Study
COMPLETED
35
74
Overall Study
NOT COMPLETED
117
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Autopsy Cohort
End-of-life subjects consenting to brain donation at autopsy. Subjects received a single intravenous injection of 370 MBq florbetapir followed by a 10-minute PET scan 50 minutes post-injection.
Specificity Cohort
Younger healthy controls presumed to be devoid of beta-amyloid plaques. Subjects received a single intravenous injection of 370 MBq florbetapir followed by a 10-minute PET scan 50 minutes post-injection.
Overall Study
Image acquisition failure
2
0
Overall Study
Invalid image or not imaged
3
0
Overall Study
Subject still living at end of study
110
0
Overall Study
Deceased with no autopsy
2
0

Baseline Characteristics

Phase III Study of the Correlation Between Florbetapir F18 PET Imaging and Amyloid Pathology in the Brain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Autopsy Cohort
n=152 Participants
End-of-life subjects consenting to brain donation at autopsy. Subjects received a single intravenous injection of 370 MBq florbetapir followed by a 10-minute PET scan 50 minutes post-injection.
Specificity Cohort
n=74 Participants
Younger healthy controls presumed to be devoid of beta-amyloid plaques. Subjects received a single intravenous injection of 370 MBq florbetapir followed by a 10-minute PET scan 50 minutes post-injection.
Total
n=226 Participants
Total of all reporting groups
Age Continuous
78.1 years
STANDARD_DEVIATION 13.35 • n=99 Participants
26.6 years
STANDARD_DEVIATION 6.50 • n=107 Participants
61.3 years
STANDARD_DEVIATION 26.84 • n=206 Participants
Sex: Female, Male
Female
81 Participants
n=99 Participants
26 Participants
n=107 Participants
107 Participants
n=206 Participants
Sex: Female, Male
Male
71 Participants
n=99 Participants
48 Participants
n=107 Participants
119 Participants
n=206 Participants
Region of Enrollment
United States
152 participants
n=99 Participants
74 participants
n=107 Participants
226 participants
n=206 Participants

PRIMARY outcome

Timeframe: at autopsy up to 12 months post-scan

Population: All subjects with a valid image who came to autopsy within 1 year of scan, minus 6 subjects who served as front-runners

Spearman's rank order correlation of the median semi-quantitative visual read of the florbetapir-PET image and the amyloid plaque density assessed post-mortem by quantitative immunohistochemistry (IHC) averaged across 6 brain regions (precuneus, parietal cortex, frontal cortex, temporal cortex, posterior cingulate, anterior cingulate). Spearman's rank order correlation ranges from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation.

Outcome measures

Outcome measures
Measure
Autopsy Cohort
n=29 Participants
End-of-life subjects consenting to brain donation at autopsy
Correlation of Florbetapir-PET Image and Amyloid Plaque Density
0.78 Correlation coefficient
Interval 0.58 to 0.89

PRIMARY outcome

Timeframe: 50-60 min after injection

Population: Per protocol, 27 subjects who were genetic carriers for ApoE e4 or whose genetic status was unknown were excluded from the analysis

Specificity of florbetapir-PET scan in younger healthy controls presumed to be negative for amyloid. Specificity results are reported as the number of subjects who had a negative scan based on majority of 3 blinded readers.

Outcome measures

Outcome measures
Measure
Autopsy Cohort
n=47 Participants
End-of-life subjects consenting to brain donation at autopsy
Specificity Analysis
Positive for amyloid
0 participants
Interval 91.0 to 100.0
Specificity Analysis
Negative for amyloid
47 participants

SECONDARY outcome

Timeframe: at autopsy up to 12 months post-scan

Population: All subjects with a valid image who came to autopsy within 1 year of scan, minus 6 subjects who served as front-runners

Spearman's rank order correlation of median visual read of the florbetapir-PET image vs. amyloid plaque density assessed post-mortem by quantitative IHC of six individual brain regions (precuneus, parietal cortex, frontal cortex, temporal cortex, posterior cingulate, anterior cingulate). Spearman's rank order correlation ranges from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation.

Outcome measures

Outcome measures
Measure
Autopsy Cohort
n=29 Participants
End-of-life subjects consenting to brain donation at autopsy
Regional Correlation Analysis
Precuneus
0.75 Correlation coefficient
Interval 0.53 to 0.88
Regional Correlation Analysis
Parietal cortex
0.77 Correlation coefficient
Interval 0.56 to 0.88
Regional Correlation Analysis
Frontal cortex
0.69 Correlation coefficient
Interval 0.44 to 0.84
Regional Correlation Analysis
Temporal cortex
0.68 Correlation coefficient
Interval 0.42 to 0.84
Regional Correlation Analysis
Posterior cingulate
0.70 Correlation coefficient
Interval 0.44 to 0.85
Regional Correlation Analysis
Anterior cingulate
0.74 Correlation coefficient
Interval 0.51 to 0.87

Adverse Events

Autopsy Cohort

Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths

Specificity Cohort

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Autopsy Cohort
n=152 participants at risk
End-of-life subjects consenting to brain donation at autopsy. Subjects received a single intravenous injection of 370 MBq florbetapir followed by a 10-minute PET scan 50 minutes post-injection.
Specificity Cohort
n=74 participants at risk
Younger healthy controls presumed to be devoid of beta-amyloid plaques. Subjects received a single intravenous injection of 370 MBq florbetapir followed by a 10-minute PET scan 50 minutes post-injection.
Respiratory, thoracic and mediastinal disorders
Respiratory failure
0.66%
1/152 • Number of events 152 • AEs were collected up to 48 hours after injection. SAEs were collected up to 30 days after injection.
0.00%
0/74 • AEs were collected up to 48 hours after injection. SAEs were collected up to 30 days after injection.

Other adverse events

Other adverse events
Measure
Autopsy Cohort
n=152 participants at risk
End-of-life subjects consenting to brain donation at autopsy. Subjects received a single intravenous injection of 370 MBq florbetapir followed by a 10-minute PET scan 50 minutes post-injection.
Specificity Cohort
n=74 participants at risk
Younger healthy controls presumed to be devoid of beta-amyloid plaques. Subjects received a single intravenous injection of 370 MBq florbetapir followed by a 10-minute PET scan 50 minutes post-injection.
Nervous system disorders
Headache
2.0%
3/152 • Number of events 3 • AEs were collected up to 48 hours after injection. SAEs were collected up to 30 days after injection.
2.7%
2/74 • Number of events 2 • AEs were collected up to 48 hours after injection. SAEs were collected up to 30 days after injection.

Additional Information

Chief Medical Officer

Avid Radiopharmaceuticals

Phone: 215-298-0700

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: GT60