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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Avid Radiopharmaceuticals
ClinicalTrials.gov Identifier:
NCT00857415
First received: March 5, 2009
Last updated: May 17, 2012
Last verified: May 2012
Results First Received: April 6, 2012  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Single Blind (Outcomes Assessor);   Primary Purpose: Diagnostic
Condition: Alzheimer's Disease
Intervention: Drug: florbetapir F 18

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
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.

Participant Flow:   Overall Study
    Autopsy Cohort     Specificity Cohort  
STARTED     152     74  
Deceased Within One Year of AV-45 Scan     37     0 [1]
COMPLETED     35     74  
NOT COMPLETED     117     0  
Image acquisition failure                 2                 0  
Invalid image or not imaged                 3                 0  
Subject still living at end of study                 110                 0  
Deceased with no autopsy                 2                 0  
[1] Subjects in the specificity cohort were not followed to autopsy



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
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.
Total Total of all reporting groups

Baseline Measures
    Autopsy Cohort     Specificity Cohort     Total  
Number of Participants  
[units: participants]
  152     74     226  
Age  
[units: years]
Mean ± Standard Deviation
  78.1  ± 13.35     26.6  ± 6.50     61.3  ± 26.84  
Gender  
[units: participants]
     
Female     81     26     107  
Male     71     48     119  
Region of Enrollment  
[units: participants]
     
United States     152     74     226  



  Outcome Measures
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1.  Primary:   Correlation of Florbetapir-PET Image and Amyloid Plaque Density   [ Time Frame: at autopsy up to 12 months post-scan ]

Measure Type Primary
Measure Title Correlation of Florbetapir-PET Image and Amyloid Plaque Density
Measure Description 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.
Time Frame at autopsy up to 12 months post-scan  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subjects with a valid image who came to autopsy within 1 year of scan, minus 6 subjects who served as front-runners

Reporting Groups
  Description
Autopsy Cohort End-of-life subjects consenting to brain donation at autopsy

Measured Values
    Autopsy Cohort  
Number of Participants Analyzed  
[units: participants]
  29  
Correlation of Florbetapir-PET Image and Amyloid Plaque Density  
[units: Correlation¬†coefficient]
Number ( 95% Confidence Interval )
  0.78  
  ( 0.58 to 0.89 )  


Statistical Analysis 1 for Correlation of Florbetapir-PET Image and Amyloid Plaque Density
Groups [1] Autopsy Cohort
Method [2] Spearman's Rank Correlation test
P Value [3] <0.0001
Correlation coefficient [4] 0.78
Standard Error of the mean ± 0.194
95% Confidence Interval ( 0.58 to 0.89 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Spearman's Rank Order Correlation of the median semiquantitative read (three readers) and the quantitative IHC measurement of cortical amyloid plaque density averaged across six brain regions.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  A one-sided test (rho > 0) was performed with a significance level of alpha=0.05 to assess a significant correlation.
[4] Other relevant estimation information:
  Asymptotic standard error and 95 percent CI used Fisher z-transformation.



2.  Primary:   Specificity Analysis   [ Time Frame: 50-60 min after injection ]

Measure Type Primary
Measure Title Specificity Analysis
Measure Description 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.
Time Frame 50-60 min after injection  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per protocol, 27 subjects who were genetic carriers for ApoE e4 or whose genetic status was unknown were excluded from the analysis

Reporting Groups
  Description
Specificity Cohort Younger healthy controls presumed to be devoid of beta-amyloid plaques

Measured Values
    Specificity Cohort  
Number of Participants Analyzed  
[units: participants]
  47  
Specificity Analysis  
[units: participants]
 
Positive for amyloid     0  
Negative for amyloid     47  


Statistical Analysis 1 for Specificity Analysis
Groups [1] Specificity Cohort
Specificity [2] 100
95% Confidence Interval ( 91 to 100 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Proportion of subjects who had a negative scan based on majority of 3 blinded readers
[2] Other relevant estimation information:
  95% CI calculated by Wilson score method



3.  Secondary:   Regional Correlation Analysis   [ Time Frame: at autopsy up to 12 months post-scan ]

Measure Type Secondary
Measure Title Regional Correlation Analysis
Measure Description 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.
Time Frame at autopsy up to 12 months post-scan  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subjects with a valid image who came to autopsy within 1 year of scan, minus 6 subjects who served as front-runners

Reporting Groups
  Description
Autopsy Cohort End-of-life subjects consenting to brain donation at autopsy

Measured Values
    Autopsy Cohort  
Number of Participants Analyzed  
[units: participants]
  29  
Regional Correlation Analysis  
[units: Correlation¬†coefficient]
Number ( 95% Confidence Interval )
 
Precuneus     0.75  
  ( 0.53 to 0.88 )  
Parietal cortex     0.77  
  ( 0.56 to 0.88 )  
Frontal cortex     0.69  
  ( 0.44 to 0.84 )  
Temporal cortex     0.68  
  ( 0.42 to 0.84 )  
Posterior cingulate     0.70  
  ( 0.44 to 0.85 )  
Anterior cingulate     0.74  
  ( 0.51 to 0.87 )  

No statistical analysis provided for Regional Correlation Analysis




  Serious Adverse Events


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  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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