Phase II Study of Florbetaben (BAY 94-9172) PET Imaging for Detection/Exclusion of Cerebral β-amyloid in Patients With Probable Alzheimer's Disease Compared to Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Piramal Imaging SA
ClinicalTrials.gov Identifier:
NCT00750282
First received: September 9, 2008
Last updated: July 15, 2014
Last verified: July 2014
  Purpose

The aim of this study is to evaluate the efficacy, safety of a single dose of BAY 94-9172 (ZK 6013443) as an investigational medicinal product (IMP) in detecting cerebral protein-plaque (amyloid beta) with positron emission tomography (PET). IMP binds to amyloidal beta protein accumulating in brain tissue already from early stages of Alzheimer's disease (AD). IMP is therefore a potential tracer to be used for detecting amyloid plaques. For each subject it is required to visit the study centre during the screening phase, on the PET imaging day and for 1 follow-up visit on the next day. A telephone call for safety follow-up will be performed 7 days after IMP administration. During the screening phase the subject's medical, neurological and surgical history, specific laboratory tests related to AD, MRI of the brain and certain neuro-psychiatric tests will be performed. Clinical safety measures (physical examinations, vital signs, electrocardiogram (ECG) and laboratory tests) will be performed on the PET imaging day before IMP injection and monitored during and after two PET imaging sessions. Clinical safety measures will be performed again on the follow-up visit next day. The results of PET imaging with IMP will be compared between probable AD patients and healthy volunteers (HV). The clinical diagnosis is based on international validated and accepted criteria and established after comprehensive clinical and neuro-psychiatric examinations


Condition Intervention Phase
Alzheimer Disease
Amyloid Beta-Protein
Drug: Florbetaben (BAY94-9172)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: An Open-label, Non-randomized, Multi-center Study to Optimize Image Assessment and Evaluate the Efficacy and Safety of BAY 94-9172 (ZK 6013443) Positron Emission Tomography (PET) for Detection/Exclusion of Cerebral Amyloid Beta in Patients With Probable Alzheimer's Disease Compared to Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by Piramal Imaging SA:

Primary Outcome Measures:
  • Specificity and Sensitivity of Florbetaben PET Scans Obtained in Part A Using Two Separate Algorithms and the Onsite Clinical Diagnosis as the Standard of Truth [ Time Frame: 90 - 110 min after investigational medical product (IMP) injection ] [ Designated as safety issue: No ]

    Part A: For the calculation of sensitivity/specificity, a patient with probable AD was expected to have a positive florbetaben PET scan which was considered a match for sensitivity. A HV was expected to have a negative florbetaben PET scan which was considered a match for specificity. Standard of truth was the onsite clinical diagnosis.

    Two Beta-Amyloid Plaque Load (BAPL) algorithms for assessing the normality/abnormality of beta-amyloid plaque load in the brain scans were used.

    Using algorithm A (Majority Read), a brain scan of a subject with a BAPL score of "1" (without beta-amyloid plaque load) or "2" (with minor beta-amyloid plaque load) was considered normal and a BAPL score of "3" (with significant beta-amyloid plaque load) was considered abnormal.

    Using algorithm B (Average), a brain scan of a subject with a BAPL score of "1" was considered normal and a brain scan with a BAPL score of "2" or "3" was considered abnormal. Algorithm B was used in Part B and in the final


  • Specificity and Sensitivity of Florbetaben PET Scans Obtained in Part B Using Two Separate Algorithms and the Onsite Clinical Diagnosis as the Standard of Truth. [ Time Frame: 90 - 110 min after IMP injection ] [ Designated as safety issue: No ]

    Part B: For the calculation of sensitivity/specificity, a patient with probable AD was expected to have a positive florbetaben PET scan, ie,abnormal scan (BAPL scores "2" or "3") which was considered a match for sensitivity. A HV was expected to have a negative florbetaben PET scan, ie,normal scan (BAPL score "1") which was considered a match for specificity.

    The clinical diagnosis was established by an independent consensus panel (CP) of experts in dementia.

    Two independent sets of PET data reads were performed. The first set was performed by a panel of three readers who received live, instructor-led training on the visual assessment procedure. The second set was performed by a panel of five separate readers who were trained on the visual assessment procedure with electronic media.



Secondary Outcome Measures:
  • Sensitivity and Specificity for All Participants Using Two Additional Imaging Windows for the Visual Assessment [ Time Frame: 45 - 60 min and 110 - 130 min after IMP injection ] [ Designated as safety issue: No ]
    PET scans from two additional imaging windows (45-60 min and 110-130 min) were visually assessed

  • Kappa Coefficient as a Measure of Agreement Between Readers Concerning the Visual Assessment of Abnormality of the Brain Scan (Based on BAPL Score) [ Time Frame: 45-60 min, 90-110 min, 110-130 min ] [ Designated as safety issue: No ]
    The agreement between 3 blinded readers concerning the visual assessment of abnormality of the brain scan (based on BAPL score) was measured by the kappa coefficient. Kappa values close to 1.0 indicate a high agreement while values close to 0 indicate random agreement.

  • Standard Uptake Value Ratios for Florbetaben Signal [ Time Frame: 90-110 min post injection ] [ Designated as safety issue: No ]
    The Standard Uptake Value Ratios for florbetaben signal in the frontal cortex, lateral temporal cortex, parietal cortex, anterior cingulate, posterior cingulate cortex, occipital cortex, and cerebellum (white matter) were determined as a quantitative measure of tracer uptake. The SUV is defined as the ratio of (1) the tissue radioactivity concentration c (in MBq/kg) at time point t, and (2) the injected activity (in MBq, extrapolated to the same time t) divided by the body weight (in kg). These SUV numbers from regions of interest were then used to derive SUV ratios (SUVR) using the SUV from the cerebellar cortex as reference.)


Enrollment: 422
Study Start Date: August 2008
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Florbetaben (BAY94-9172) Drug: Florbetaben (BAY94-9172)
Healthy volunteers and patients with probable Alzheimer's disease receiving single injection of investigational medicinal product BAY 94-9172 followed by subsequent PET imaging sessions

  Eligibility

Ages Eligible for Study:   55 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Each subject / Healthy volunteer (HV) who meets the following criteria will be eligible for enrollment into the study:

    • Is a man or woman and is > 55 of age, whereby females must be without childbearing potential (confirmed by either: age >/= 60; or history of hysterectomy, or last spontaneous bleeding at least 2 years prior to the study start)
    • Has at least 6 years of education
    • Is able to provide informed consent, understand the information provided on the purpose and conduct of the trial and to comply with study procedures
    • Possesses a general health that permits adequate compliance with all study procedures
    • The subject, or the subject and caregiver (for probable AD patients) will be compliant and have a high probability of completing the study
    • Informed consent has been signed and dated (with time) by the subject and/or the subject's caregiver (for probable AD patients)
  • Inclusion criteria for HV only:

    • Has no evidence of cognitive impairment
    • Has MRI brain scan that has been judged as "normal" (age- appropriate)
  • Inclusion criteria for patients with AD only:

    • Presents with positive assessment for dementia of Alzheimer's type
    • Does not fulfill the criteria Dementia with Lewy Bodies (DLB) or Vascular Dementia (VaD)
    • MRI brain scan findings that do not reveal changes indicative of stroke and/or generalized cerebrovascular disease
    • Has a caregiver that is willing and able to attend all study visits and perform the psychometric tests requiring the presence of a caregiver

Exclusion Criteria:

  • Has any contraindication to MRI examination scan
  • Is scheduled for surgery and/or another invasive procedure within the time period of up to 24 hours following IMP application
  • Is allergic to the IMP or any of its constituents and/or has a history of severe allergic reactions to drugs or allergens (e.g. patients / volunteers with allergic asthma)
  • is critically ill and/or medically unstable and whose clinical course during the observation period is unpredictable
  • Has a history of exposure to any radiation >15 milli Sieverts (mSv)/year (e.g. occupational or radiation therapy)
  • Is receiving drug therapy or other treatment that is known to lead to greatly fluctuating values of the hematological or chemical laboratory parameters or to severe side effects (e.g. chemotherapy)
  • Has been previously enrolled in this study or participated in a clinical study involving an investigational pharmaceutical product within 30 days prior to screening, and/or any radiopharmaceutical
  • Has a brain tumor or other intracranial lesion, a disturbance of cerebro-spinal fluid (CSF) circulation (e.g., normal pressure hydrocephalus) and/or a history of head trauma or brain surgery
  • Has an inflammatory or infectious central nervous system (CNS) disease, e.g. multiple sclerosis, HIV, syphilis, or Creutzfeldt-Jacob disease
  • Has a history, physical, laboratory or imaging findings indicative of a neurological or psychiatric illness
  • Has another disease that can cause disturbance of brain function (e.g. vitamin B12 or folic acid deficiency, disturbed thyroid function)
  • Has a history of alcohol or drug abuse
  • Has history of severe persistent depression
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00750282

Locations
United States, Arizona
Sun City, Arizona, United States, 85351
United States, California
Stanford, California, United States, 94305
United States, Connecticut
New Haven, Connecticut, United States, 06510
United States, New York
Bronx, New York, United States, 10461
New York, New York, United States, 10016
New York, New York, United States, 10032
United States, Rhode Island
Providence, Rhode Island, United States, 02906
Australia, New South Wales
Westmead, New South Wales, Australia, 2145
Australia, South Australia
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Heidelberg, Victoria, Australia, 3084
Germany
Erlangen, Bayern, Germany, 91054
München, Bayern, Germany, 81675
München, Bayern, Germany, 81377
Essen, Nordrhein-Westfalen, Germany, 45122
Jülich, Nordrhein-Westfalen, Germany, 52425
Münster, Nordrhein-Westfalen, Germany, 48149
Dresden, Sachsen, Germany, 01307
Leipzig, Sachsen, Germany, 04103
Berlin, Germany, 13125
Japan
Kobe, Hyogo, Japan, 650-0017
Kobe, Hyogo, Japan, 650-0047
Bunkyo-ku, Tokyo, Japan, 113-8603
Switzerland
Zürich, Switzerland, 8091
Sponsors and Collaborators
Piramal Imaging SA
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications:
Responsible Party: Piramal Imaging SA
ClinicalTrials.gov Identifier: NCT00750282     History of Changes
Other Study ID Numbers: 311741, 2007-002256-42, 311741
Study First Received: September 9, 2008
Results First Received: June 16, 2014
Last Updated: July 15, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Switzerland: Swissmedic
Australia: Department of Health and Ageing Therapeutic Goods Administration
Japan: Pharmaceuticals and Medical Devices Agency
United States: Food and Drug Administration

Keywords provided by Piramal Imaging SA:
Alzheimer Disease
Amyloid beta-Protein

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on August 28, 2014