Trial Outcomes & Findings for Autopsy Follow-up of Subjects Previously Imaged With Florbetapir F 18 (18F-AV-45) PET in Trial 18F-AV-45-A07 (NCT NCT01447719)

Results Overview

Sensitivity of florbetapir-PET scan to detect moderate to frequent amyloid plaques. Plaque density was calculated using CERAD (Consortium to Establish a Registry for AD) criteria. Florbetpir-PET scans were read by five independent readers blinded to clinical information using the binary read method (amyloid positive/negative).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

110 participants

Primary outcome timeframe

at autopsy within 24 months of florbetapir PET scan

Results posted on

2025-03-21

Participant Flow

Demographic results are only provided for primary analysis populations of subjects who came to autopsy. Demographic characteristics for the entire population of 152 subjects are reported with the results of study A07 (NCT00857415).

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.
Overall Study STARTED	152
Overall Study Valid AV-45 Scan Acquired	147
Overall Study Deceased <2 Years After AV-45 Scan	66
Overall Study COMPLETED	59
Overall Study NOT COMPLETED	93

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.
Overall Study Image acquisition failure	2
Overall Study Invalid image or not imaged	3
Overall Study Subject still living at end of study	79
Overall Study Withdrawal by Subject	2
Overall Study Family withdrew autopsy consent	7

Baseline Characteristics

Autopsy Follow-up of Subjects Previously Imaged With Florbetapir F 18 (18F-AV-45) PET in Trial 18F-AV-45-A07

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Autopsy Population n=59 Participants Group of subjects with valid images who came to autopsy within 2 years of scan
Age, Continuous	79.4 years STANDARD_DEVIATION 12.64 • n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants
Region of Enrollment United States	59 participants n=5 Participants
Baseline clinical diagnosis AD diagnosis	29 participants n=5 Participants
Baseline clinical diagnosis Other dementing disorder	13 participants n=5 Participants
Baseline clinical diagnosis No history of cognitive impairment	12 participants n=5 Participants
Baseline clinical diagnosis Mild cognitive impairment	5 participants n=5 Participants

PRIMARY outcome

Timeframe: at autopsy within 24 months of florbetapir PET scan

Population: 39 of 59 subjects from all autopsy population had moderate to frequent neuritic plaques at autopsy

Sensitivity of florbetapir-PET scan to detect moderate to frequent amyloid plaques. Plaque density was calculated using CERAD (Consortium to Establish a Registry for AD) criteria. Florbetpir-PET scans were read by five independent readers blinded to clinical information using the binary read method (amyloid positive/negative).

Outcome measures

Outcome measures
Measure	Subjects With Moderate or Frequent Plaques at Autopsy n=39 Participants Group of subjects with valid images who came to autopsy within 2 years of scan and had moderate to frequent neuritic plaques at autopsy (probable AD or definite AD)
Sensitivity Analysis in All Autopsy Population Florbetapir PET positive (majority interpretation)	36 participants
Sensitivity Analysis in All Autopsy Population Florbetapir PET negative (majority interpretation)	3 participants

PRIMARY outcome

Timeframe: at autopsy within 24 months of florbetapir PET scan

Population: 20 of 59 subjects from the all autopsy population had no or sparse neuritic plaques at autopsy

Specificity of florbetapir-PET scan to detect moderate to frequent amyloid plaques. Plaque density was calculated using CERAD criteria. Florbetpir-PET scans were read by five independent readers blinded to clinical information using the binary read method (amyloid positive/negative).

Outcome measures

Outcome measures
Measure	Subjects With Moderate or Frequent Plaques at Autopsy n=20 Participants Group of subjects with valid images who came to autopsy within 2 years of scan and had moderate to frequent neuritic plaques at autopsy (probable AD or definite AD)
Specificity Analysis in All Autopsy Population Florbetapir PET positive (majority interpretation)	0 participants
Specificity Analysis in All Autopsy Population Florbetapir PET negative (majority interpretation)	20 participants

PRIMARY outcome

Timeframe: at autopsy within 24 months of florbetapir PET scan

Spearman's rank order correlation of the median 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	Subjects With Moderate or Frequent Plaques at Autopsy n=59 Participants Group of subjects with valid images who came to autopsy within 2 years of scan and had moderate to frequent neuritic plaques at autopsy (probable AD or definite AD)
Correlation of Florbetapir-PET Image and Amyloid Plaque Density	0.76 Correlation coefficient Interval 0.62 to 0.85

SECONDARY outcome

Timeframe: at autopsy within 12 months of florbetapir PET scan

Population: 28 of 46 subjects who died within 1 year of scan had moderate to frequent neuritic plaques at autopsy

Sensitivity of florbetapir-PET scan to detect moderate to frequent amyloid plaques. Plaque density was calculated using CERAD criteria. Florbetpir-PET scans were read by five independent readers blinded to clinical information using the binary read method (amyloid positive/negative).

Outcome measures

Outcome measures
Measure	Subjects With Moderate or Frequent Plaques at Autopsy n=28 Participants Group of subjects with valid images who came to autopsy within 2 years of scan and had moderate to frequent neuritic plaques at autopsy (probable AD or definite AD)
Sensitivity Analysis in Subjects With Autopsy Within 1 Year of Scan Florbetapir PET positive (majority interpretation)	27 participants
Sensitivity Analysis in Subjects With Autopsy Within 1 Year of Scan Florbetapir PET negative (majority interpretation)	1 participants

SECONDARY outcome

Timeframe: at autopsy within 12 months of florbetapir PET scan

Population: 18 of 46 subjects who died within 1 year of scan had no or sparse neuritic plaques at autopsy

Specificity of florbetapir-PET scan to detect moderate to frequent amyloid plaques. Plaque density was calculated using CERAD criteria. Florbetpir-PET scans were read by five independent readers blinded to clinical information using the binary read method (amyloid positive/negative).

Outcome measures

Outcome measures
Measure	Subjects With Moderate or Frequent Plaques at Autopsy n=18 Participants Group of subjects with valid images who came to autopsy within 2 years of scan and had moderate to frequent neuritic plaques at autopsy (probable AD or definite AD)
Specificity Analysis in Subjects With Autopsy Within 1 Year of Scan Florbetapir PET positive (majority interpretation)	0 participants
Specificity Analysis in Subjects With Autopsy Within 1 Year of Scan Florbetapir PET negative (majority interpretation)	18 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: at autopsy within 24 months of florbetapir PET scan

Median sensitivity and specificity for 5 independent readers to detect moderate to frequent amyloid plaques (per CERAD criteria).

Outcome measures

Outcome measures
Measure	Subjects With Moderate or Frequent Plaques at Autopsy n=59 Participants Group of subjects with valid images who came to autopsy within 2 years of scan and had moderate to frequent neuritic plaques at autopsy (probable AD or definite AD)
Median Sensitivity and Specificity vs. CERAD Diagnosis Sensitivity	92 percentage of true positives/negatives Interval 69.0 to 95.0
Median Sensitivity and Specificity vs. CERAD Diagnosis Specificity	95 percentage of true positives/negatives Interval 90.0 to 100.0

OTHER_PRE_SPECIFIED outcome

Timeframe: at autopsy within 24 months of florbetapir PET scan

Reader results (number of false negatives and number of false positives) for blinded independent readers. There were a total of 39 positive and 20 negative scans based on histopathology at autopsy.

Outcome measures

Outcome measures
Measure	Subjects With Moderate or Frequent Plaques at Autopsy n=59 Participants Group of subjects with valid images who came to autopsy within 2 years of scan and had moderate to frequent neuritic plaques at autopsy (probable AD or definite AD)
Individual Reader Results (All Scans With Autopsy) Reader 1 - False Negatives	3 florbetapir PET scans
Individual Reader Results (All Scans With Autopsy) Reader 1 - False Positives	1 florbetapir PET scans
Individual Reader Results (All Scans With Autopsy) Reader 2 - False Negatives	2 florbetapir PET scans
Individual Reader Results (All Scans With Autopsy) Reader 2 - False Positives	1 florbetapir PET scans
Individual Reader Results (All Scans With Autopsy) Reader 3 - False Negatives	5 florbetapir PET scans
Individual Reader Results (All Scans With Autopsy) Reader 3 - False Positives	1 florbetapir PET scans
Individual Reader Results (All Scans With Autopsy) Reader 4 - False Negatives	3 florbetapir PET scans
Individual Reader Results (All Scans With Autopsy) Reader 4 - False Positives	0 florbetapir PET scans
Individual Reader Results (All Scans With Autopsy) Reader 5 - False Negatives	12 florbetapir PET scans
Individual Reader Results (All Scans With Autopsy) Reader 5 - False Positives	2 florbetapir PET scans

OTHER_PRE_SPECIFIED outcome

Timeframe: at autopsy within 12 months of florbetapir PET scan

Population: Includes only those subjects with time from scan to autopsy less than one year.

Reader results (number of false negatives and number of false positives) for blinded independent readers. There were a total of 28 positive and 18 negative scans based on histopathology at autopsy.

Outcome measures

Outcome measures
Measure	Subjects With Moderate or Frequent Plaques at Autopsy n=46 Participants Group of subjects with valid images who came to autopsy within 2 years of scan and had moderate to frequent neuritic plaques at autopsy (probable AD or definite AD)
Individual Reader Results (Autopsy Within 1 Year of Scan) Reader 1 - False Negatives	1 florbetapir PET scans
Individual Reader Results (Autopsy Within 1 Year of Scan) Reader 1 - False Positives	1 florbetapir PET scans
Individual Reader Results (Autopsy Within 1 Year of Scan) Reader 2 - False Negatives	0 florbetapir PET scans
Individual Reader Results (Autopsy Within 1 Year of Scan) Reader 2 - False Positives	1 florbetapir PET scans
Individual Reader Results (Autopsy Within 1 Year of Scan) Reader 3 - False Negatives	3 florbetapir PET scans
Individual Reader Results (Autopsy Within 1 Year of Scan) Reader 3 - False Positives	0 florbetapir PET scans
Individual Reader Results (Autopsy Within 1 Year of Scan) Reader 4 - False Negatives	1 florbetapir PET scans
Individual Reader Results (Autopsy Within 1 Year of Scan) Reader 4 - False Positives	0 florbetapir PET scans
Individual Reader Results (Autopsy Within 1 Year of Scan) Reader 5 - False Negatives	7 florbetapir PET scans
Individual Reader Results (Autopsy Within 1 Year of Scan) Reader 5 - False Positives	2 florbetapir PET scans

Adverse Events

Autopsy Cohort

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Chief Medical Officer

Avid Radiopharmaceuticals

Phone: 215-298-0700

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60