Comparison of PET Amyloid Imaging in Japanese and Western Subjects

May 3, 2017 updated by: GE Healthcare

An Open-label Study to Assess Brain Uptake and Safety of Flutemetamol F 18 Injection in Japanese Subjects With Probable Alzheimer's Disease, Subjects With Amnestic Mild Cognitive Impairment and Healthy Volunteers

This was a Phase 2, multicenter study to assess the extent and patterns of [18F] flutemetamol uptake in the brains of 3 groups of Japanese subjects: healthy volunteers (HV), amnestic mild cognitive impairment (aMCI), and probable Alzheimer's disease (pAD), and to assess the reproducibility of brain uptake and of image interpretation. Subjects underwent open-label intravenous (i.v.) administration of Flutemetamol F 18 Injection and Positron emission tomography (PET) imaging of the brain. Blinded visual image reads were performed by 10 independent board-certified readers (5 Japanese and 5 non-Japanese) with nuclear medicine image interpretation experience. The blinded visual assessments were compared with the subject's clinical diagnoses, and the agreement between the image interpretations made by the 2 groups of readers (Japanese and non-Japanese) was determined.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This was a Phase 2, multicenter study to assess the extent and patterns of [18F] flutemetamol uptake in the brains of 3 groups of Japanese subjects: HV, aMCI, and pAD, and to assess the reproducibility of brain uptake and of image interpretation. The 3 comparison groups (HV, aMCI, and pAD) were defined by the subjects' main clinical diagnoses at study entry. Subjects underwent diagnostic quality anatomic brain magnetic resonance imaging (MRI), followed by open-label intravenous (i.v) administration of Flutemetamol F 18 Injection and PET imaging of the brain. Blinded visual image reads were performed by 10 independent board-certified readers (5 Japanese and 5 non-Japanese) with nuclear medicine image interpretation experience. The blinded visual assessments were compared with the subject's clinical diagnoses, and the agreement between the image interpretations made by the 2 groups of readers (Japanese and non-Japanese) was determined. Blinded visual assessments were also compared to quantitative image assessments (standardized uptake value ratio [SUVRs]). Inter-reader and intra-reader agreement was also assessed. Test-retest variability was evaluated following a second administration of Flutemetamol F 18 Injection given to a subset (N=5) of pAD subjects between 1 and 4 weeks after their first administration of Flutemetamol F 18 Injection.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
70

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

25 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

General inclusion criteria for all subjects:

  1. The subject had at least 6 years of education.
  2. The subject was of first-order Japanese descent.
  3. The subject exhibited adequate visual, auditory and communication capabilities, and was willing and able to complete standard tests of cognitive function.
  4. The subject's general health was adequate to comply with all study procedures, as ascertained by review of their medical history, and laboratory and physical examinations, which was performed within 45 days before the first administration of Flutemetamol F 18 Injection.
  5. The subject (and the caregiver, if relevant) was/were compliant and had a high probability of completing the study in the opinion of the investigator.
  6. Women were either surgically sterile (had a documented bilateral oophorectomy and/or documented hysterectomy) or were postmenopausal (cessation of menses for more than 2 years).
  7. Informed consent was signed and dated by the subject and/or subject's legally acceptable representative, if applicable, in accordance with local regulations.

Inclusion criteria specific for HV:

  1. The subject was 25 years or older at the time of obtaining informed consent.
  2. The subject had no evidence of cognitive impairment by medical history.
  3. The subject had a Mini-Mental State Examination (MMSE) score of =< 27.
  4. The subject had a Clinical Dementia Rating (CDR) of 0.
  5. The subject had an MRI image as part of the screening visit of sufficient diagnostic quality and consistent with normal brain function (details provided in the associated Imaging Manual) for volume of interest (VOI) definition and partial volume correction.

Inclusion criteria specific for subjects with pAD:

  1. The subject was 55 years or older at the time of obtaining informed consent.
  2. The subject met National Institute of Neurological and Communicative Disorders and Stroke; Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for clinical pAD and Diagnostic and Statistical Manual of Mental Disorders (DSM-IV]), 4th Edition, criteria for AD (DSM-IV criteria, American Psychiatric Association 1994).
  3. The subject had an MMSE score of 15 to 26 (inclusive) and a CDR of 0.5, 1 or 2.
  4. The subject had a score of =< 4 on the Modified Hachinski Ischemic scale.
  5. The subject had an appropriate caregiver capable of accompanying the subject on all study visits.
  6. The subject had an MRI image as part of the screening visit consistent with the diagnosis of pAD and of sufficient diagnostic quality (details provided in the associated Imaging Manual) for VOI definition and partial volume correction.

Inclusion criteria specific for subjects with aMCI:

  1. The subject was 55 years or older at the time of obtaining informed consent.
  2. The subject met Petersen criteria for aMCI.
  3. The subject had an MMSE score of 27 to 30 (inclusive) and a CDR of 0 to 0.5.
  4. The subject had a score of =< 4 on the Modified Hachinski Ischemic Scale.
  5. The subject had an appropriate caregiver/companion capable of accompanying the subject on all study visits if necessary and applicable according to local regulations.
  6. The subject had an MRI image as part of the screening visit consistent with the diagnosis of aMCI and of sufficient diagnostic quality (details provided in Imaging Manual) for VOI definition and partial volume correction.

Exclusion Criteria:

  1. The subject was not able to complete the study procedures as judged by the investigator.
  2. The subject had received ionizing radiation exposure of more than 1 mSv (except arising from head computed tomography [CT]) in the last 12 months or was determined unsuitable by the investigator as a result of radiation exposure in the past.
  3. The subject had a known or suspected hypersensitivity/allergy to [18F] flutemetamol or to any of its excipients.
  4. Female subjects who were of childbearing potential, pregnant, or nursing.
  5. The subject had a history of alcohol and/or drug abuse within the last 2 years based upon a review of medical records or reported medical history.
  6. The subject had a contraindication for MRI or PET (including, but not limited to, claustrophobia, pacemaker, the presence of metallic fragments, or cochlear implant).
  7. The subject had participated in a clinical trial using an investigational medicinal product (IMP) within 30 days of dosing.
  8. The subject had positive serology for HBs antigen, HCV antibody, HIV antibody or serologic test for syphilis.
  9. The subject regularly took medication with a known anticholinergic effect (which could have impaired memory) within the prior 3 months.
  10. The subject had a history of head injury associated with significant loss of consciousness that, in the opinion of the investigator, would have interfered with the interpretation of PET images.

Exclusion criteria specific for HV:

  1. The subject had any clinically significant medical or neurological condition or any clinically significant abnormality on physical, neurological or laboratory examination.
  2. The subject had a family history of pAD (more than 1 first degree relative with the diagnosis of pAD).

Exclusion criteria specific for subjects with pAD and aMCI:

  1. The subject had a significant neurological or psychiatric disorder (including, but not limited to, major depression, schizophrenia, mania, etc.) other than pAD that may have affected cognition.
  2. The subject had a previous history of clinically evident stroke or significant cerebrovascular disease on brain imaging.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: DIAGNOSTIC
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Healthy volunteers
185 MBq [18F] Flutemetamol
Drug: [18F] Flutemetamol
PET brain imaging and Magnetic resonance brain imaging
Other Names:
  • GE067
EXPERIMENTAL: Mild cognitive impairment
185 MBq [18F] Flutemetamol
Drug: [18F] Flutemetamol
PET brain imaging and Magnetic resonance brain imaging
Other Names:
  • GE067
EXPERIMENTAL: Alzheimer's Disease
185 MBq [18F] Flutemetamol
Drug: [18F] Flutemetamol
PET brain imaging and Magnetic resonance brain imaging
Other Names:
  • GE067

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Blinded Visual Assessment of Positron Emission Tomography (PET) Imaging and Clinical Diagnosis by Non-Japanese Readers
Time Frame: Up to 90 minutes after investigational medicinal product (IMP) administration
The performance of Flutemetanol F 18 injection in participants was determined by evaluation of the level of association between the blinded visual assessment of a participant's brain image and the participant's clinical diagnosis by 5 non-Japanese readers, who classified each participant's images as either normal or abnormal (raised) Flutemetanol F 18 uptake.
Up to 90 minutes after investigational medicinal product (IMP) administration
Blinded Visual Assessment of Positron Emission Tomography (PET) Imaging and Clinical Diagnosis by Japanese Readers
Time Frame: Up to 90 minutes after IMP administration
The performance of Flutemetanol F 18 injection in participants was determined by evaluation of the level of association between the blinded visual assessment of a participant's brain image and the participant's clinical diagnosis by 5 Japanese readers, who classified each participant's images as either normal or abnormal (raised) Flutemetanol F 18 uptake.
Up to 90 minutes after IMP administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
GE Healthcare

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Levent Ture, GE Healthcare

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2012

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2013

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 15, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 22, 2016

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 24, 2016

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 5, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 3, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GE067-017

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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