Florbetapir Calibration to the Centiloid Scale

Sponsor
Avid Radiopharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT02120664
Collaborator
(none)
35
2
2
17
17.5
1

Study Details

Study Description

Brief Summary

This study is designed to demonstrate the conversion of florbetapir (18F) Positron Emission Tomography (PET) Standard Uptake Value ratio (SUVr) to Centiloid units.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
35 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Diagnostic
Official Title:
A Multicenter, Multicountry Study to Calibrate Florbetapir (18F) PET Imaging Data to the Centiloid Scale Based on 11C-PiB
Study Start Date :
Apr 1, 2014
Actual Primary Completion Date :
Sep 1, 2015
Actual Study Completion Date :
Sep 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Amyloid Negative Subjects

Approximately 10 cognitively normal young subjects will receive a single i.v. bolus injection of approximately 370 megabecquerel (MBq) (10 millicurie [mCi]) florbetapir (18F) and a single i.v. bolus injection of approximately 555 MBq (15 mCi) 11C-PiB.

Drug: Florbetapir (18F)
Other Names:
  • Florbetapir F 18
  • Amyvid
  • 18F-AV-45
  • Drug: 11C-PiB
    Other Names:
  • Pittsburgh Compound B
  • Experimental: Amyloid Positive Subjects

    Approximately 25 subjects with a range of amyloid density comprised of subjects clinically diagnosed with Alzheimer's Disease (AD) and subjects at risk for elevated amyloid density will receive a single i.v. bolus injection of approximately 370 MBq (10 mCi) florbetapir (18F) and a single i.v. bolus injection of approximately 555 MBq (15 mCi) 11C-PiB.

    Drug: Florbetapir (18F)
    Other Names:
  • Florbetapir F 18
  • Amyvid
  • 18F-AV-45
  • Drug: 11C-PiB
    Other Names:
  • Pittsburgh Compound B
  • Outcome Measures

    Primary Outcome Measures

    1. Florbetapir SUVr Conversion to Centiloid Units [up to 70 minutes post injection]

      Conversion of florbetapir (18F) positron emission tomography (PET) standard uptake value ratio (SUVr) to Centiloid units. The Centiloid is anchored at values of 0 and 100 corresponding to the median Pittsburgh Compound B (11C-PiB) SUVr value for a representative group of young (<45) cognitively and medically healthy control subjects (YHC) and the median SUVr value for a representative group of 11C-PiB positive patients diagnosed with Alzheimer's disease, respectively. A cortical average to cerebellum SUVr was used for this outcome measure.

    Secondary Outcome Measures

    1. Correlation of Florbetapir (18F) Centiloid and 11C-PiB Centiloid [up to 70 minutes post injection]

      Correlation coefficient between 11C-PiB and florbetapir (18F) SUVr as converted to centiloid units. The Centiloid is anchored at values of 0 and 100 corresponding to the median Pittsburgh Compound B (11C-PiB) SUVr value for a representative group of young (<45) cognitively and medically healthy control subjects (YHC) and the median SUVr value for a representative group of 11C-PiB positive patients diagnosed with Alzheimer's disease, respectively. A cortical average to cerebellum SUVr was used for this outcome measure.

    2. Variability of PET Images in Young Healthy Control Subjects. [up to 70 minutes post injection]

      Coefficient of variation for 11C-PiB and florbetapir (18F) SUVr. A cortical average to cerebellum SUVr was used for this outcome measure.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    21 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    • Cognitively Normal Subjects

    • Males or females ≥ 21 and ≤ 45 years of age

    • Mini-mental state examination (MMSE) ≥ 29

    • Clinically Diagnosed AD Subject

    • Males or females ≥ 50 years of age

    • Meet clinical criteria for dementia due to probable AD

    • MMSE ≥ 16 and ≤ 26

    • Possible AD Subject

    • Males or females ≥ 50 years of age

    • Meet clinical criteria for dementia due to possible AD

    • MMSE ≥ 16 and ≤ 26

    • MCI Subject

    • Males or females ≥ 60 years of age with cognitive impairment (not dementia)

    • MMSE >24 and <29

    • At Risk Elderly Subject

    • Cognitively normal males or females that are known ApoE4 carriers and ≥ 75 years of age

    • MMSE ≥ 27

    Exclusion Criteria:
    • Have had or currently have a diagnosis of neurodegenerative disorders other than AD

    • Have a current serious or unstable illness that could interfere with completion of the study

    • Subject has a known brain lesion, pathology or traumatic brain injury

    • Have received or participated in a trial with investigational medications in the past 30 days

    • Have had a radiopharmaceutical imaging or treatment procedure within 7 days of study imaging session

    • Females of childbearing potential who are not surgically sterile, not refraining from sexual activity or not using reliable methods of contraception

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Pittsburgh Pennsylvania United States 15213
    2 Research Site Heidelberg Victoria Australia 3084

    Sponsors and Collaborators

    • Avid Radiopharmaceuticals

    Investigators

    • Study Chair: Chief Medical Officer, Avid Radiopharmaceuticals, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Avid Radiopharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT02120664
    Other Study ID Numbers:
    • 18F-AV-45-A22
    First Posted:
    Apr 23, 2014
    Last Update Posted:
    Mar 9, 2017
    Last Verified:
    Jan 1, 2017
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details First subject enrolled: 14 April 2014; Last subject completed: 18 September 2015
    Pre-assignment Detail
    Arm/Group Title Clincally Diagnosed AD Possible AD Mild Cognitive Impairment (MCI) At Risk Elderly Young Healthy Controls (YHC)
    Arm/Group Description Patients meeting clinical criteria for dementia due to probable Alzheimer's Disease (AD) Patients meeting clinical criteria for dementia due to possible Alzheimer's Disease Patients with a clinical diagnosis of Mild Cognitive Impairment (MCI) and not dementia. Age is 60 years or greater Elderly patients, 75 years or older, who are known ApoE4 gene carriers, and cognitively normal Cognitively normal young subjects between 21 and 45 years of age (inclusive)
    Period Title: Overall Study
    STARTED 10 4 7 4 10
    COMPLETED 10 4 7 3 10
    NOT COMPLETED 0 0 0 1 0

    Baseline Characteristics

    Arm/Group Title Clincally Diagnosed AD Possible AD Mild Cognitive Impairment (MCI) At Risk Elderly Young Healthy Controls (YHC) Total
    Arm/Group Description Patients meeting clinical criteria for dementia due to probable Alzheimer's Disease (AD) Patients meeting clinical criteria for dementia due to possible Alzheimer's Disease Patients with a clinical diagnosis of Mild Cognitive Impairment (MCI) and not dementia. Age is 60 years or greater Elderly patients, 75 years or older, who are known ApoE4 gene carriers, and cognitively normal Cognitively normal young subjects between 21 and 45 years of age (inclusive) Total of all reporting groups
    Overall Participants 10 4 7 4 10 35
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    69.2
    (4.94)
    66
    (4.76)
    79.9
    (8.47)
    79.3
    (2.5)
    27.3
    (4.83)
    60.1
    (22.28)
    Sex: Female, Male (Count of Participants)
    Female
    5
    50%
    2
    50%
    1
    14.3%
    0
    0%
    7
    70%
    15
    42.9%
    Male
    5
    50%
    2
    50%
    6
    85.7%
    4
    100%
    3
    30%
    20
    57.1%
    Mini Mental Status Exam (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    23.7
    (2.45)
    21.8
    (4.92)
    26.4
    (1.27)
    29.3
    (0.96)
    29.5
    (0.53)
    26.3
    (3.55)

    Outcome Measures

    1. Primary Outcome
    Title Florbetapir SUVr Conversion to Centiloid Units
    Description Conversion of florbetapir (18F) positron emission tomography (PET) standard uptake value ratio (SUVr) to Centiloid units. The Centiloid is anchored at values of 0 and 100 corresponding to the median Pittsburgh Compound B (11C-PiB) SUVr value for a representative group of young (<45) cognitively and medically healthy control subjects (YHC) and the median SUVr value for a representative group of 11C-PiB positive patients diagnosed with Alzheimer's disease, respectively. A cortical average to cerebellum SUVr was used for this outcome measure.
    Time Frame up to 70 minutes post injection

    Outcome Measure Data

    Analysis Population Description
    All participants receiving both a florbetapir and a PiB scan per protocol. One subject in the possible AD group did not complete a florbetapir scan due to excessive movement. One subject in the at risk elderly group elected to leave the study before the second PET scan.
    Arm/Group Title Clincally Diagnosed AD Possible AD Mild Cognitive Impairment (MCI) At Risk Elderly Young Healthy Controls (YHC)
    Arm/Group Description Patients meeting clinical criteria for dementia due to probable Alzheimer's Disease (AD) Patients meeting clinical criteria for dementia due to possible Alzheimer's Disease Patients with a clinical diagnosis of Mild Cognitive Impairment (MCI) and not dementia. Age is 60 years or greater Elderly patients, 75 years or older, who are known ApoE4 gene carriers, and cognitively normal Cognitively normal young subjects between 21 and 45 years of age (inclusive)
    Measure Participants 10 3 7 3 10
    Mean (Standard Deviation) [centiloid]
    82.44
    (45.623)
    50.75
    (60.383)
    81.19
    (66.357)
    14.93
    (35.885)
    5.24
    (11.981)
    2. Secondary Outcome
    Title Correlation of Florbetapir (18F) Centiloid and 11C-PiB Centiloid
    Description Correlation coefficient between 11C-PiB and florbetapir (18F) SUVr as converted to centiloid units. The Centiloid is anchored at values of 0 and 100 corresponding to the median Pittsburgh Compound B (11C-PiB) SUVr value for a representative group of young (<45) cognitively and medically healthy control subjects (YHC) and the median SUVr value for a representative group of 11C-PiB positive patients diagnosed with Alzheimer's disease, respectively. A cortical average to cerebellum SUVr was used for this outcome measure.
    Time Frame up to 70 minutes post injection

    Outcome Measure Data

    Analysis Population Description
    All participants receiving both a florbetapir and a PiB scan per protocol. One subject in the possible AD group did not complete the florbetapir scan due to excessive movement. One subject in the at risk elderly group elected to leave the study before the second PET scan.
    Arm/Group Title Clincally Diagnosed AD Possible AD Mild Cognitive Impairment (MCI) At Risk Elderly Young Healthy Controls (YHC)
    Arm/Group Description Patients meeting clinical criteria for dementia due to probable Alzheimer's Disease (AD) Patients meeting clinical criteria for dementia due to possible Alzheimer's Disease Patients with a clinical diagnosis of Mild Cognitive Impairment (MCI) and not dementia. Age is 60 years or greater Elderly patients, 75 years or older, who are known ApoE4 gene carriers, and cognitively normal Cognitively normal young subjects between 21 and 45 years of age (inclusive)
    Measure Participants 10 3 7 3 10
    Florbetapir
    82.44
    (45.623)
    50.75
    (60.383)
    81.19
    (66.357)
    14.93
    (35.885)
    5.24
    (11.981)
    11C-PiB
    87.18
    (41.105)
    54.52
    (56.511)
    74.33
    (57.597)
    26.39
    (37.464)
    0.73
    (2.414)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Clincally Diagnosed AD, Possible AD, Mild Cognitive Impairment (MCI), At Risk Elderly, Young Healthy Controls (YHC)
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter R squared
    Estimated Value 0.907
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Variability of PET Images in Young Healthy Control Subjects.
    Description Coefficient of variation for 11C-PiB and florbetapir (18F) SUVr. A cortical average to cerebellum SUVr was used for this outcome measure.
    Time Frame up to 70 minutes post injection

    Outcome Measure Data

    Analysis Population Description
    Young healthy controls enrolled in the study
    Arm/Group Title PiB SUVR Variability Florbetapir SUVR Variability
    Arm/Group Description Variability of standardized uptake value ratio (SUVR) for PiB scans in young healthy controls Variability of standardized uptake value ratio (SUVR) for florbetapir scans in young healthy controls
    Measure Participants 10 10
    Mean (Standard Deviation) [SUVr]
    1.01
    (0.026)
    0.98
    (0.066)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Clincally Diagnosed AD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Coefficient of Variation
    Estimated Value 2.53
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Possible AD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Coefficient of Variation
    Estimated Value 6.69
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame within 48 hours of scan as noted by group title
    Adverse Event Reporting Description
    Arm/Group Title Florbetapir Only PiB Only Both Total
    Arm/Group Description Events occurring within 48 hours following florbetapir scans only Events occurring within 48 hours of PiB scans only Events occurring within 48 hours of both florbetapir and PiB scans Events following Florbetapir (florbetapir only and both)
    All Cause Mortality
    Florbetapir Only PiB Only Both Total
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Florbetapir Only PiB Only Both Total
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/34 (0%) 0/35 (0%) 0/34 (0%) 0/34 (0%)
    Other (Not Including Serious) Adverse Events
    Florbetapir Only PiB Only Both Total
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/34 (0%) 0/35 (0%) 0/34 (0%) 0/34 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Avid Radiopharmaceuticals, Inc.
    Phone 215-298-0700
    Email clinicaloperations@avidrp.com
    Responsible Party:
    Avid Radiopharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT02120664
    Other Study ID Numbers:
    • 18F-AV-45-A22
    First Posted:
    Apr 23, 2014
    Last Update Posted:
    Mar 9, 2017
    Last Verified:
    Jan 1, 2017